Wilmington, Delaware, United States, Transparency Market Research Inc.: Cell line development is an important technology in life sciences. Stable cell lines are used for various applications including monoclonal antibody and recombinant protein productions, gene functional studies, and drug screening

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Manual screening method is a traditional method used for cell line development. This method is tend to be disadvantageous as it is labor-intensive and time-consuming. Automation in tools used for cell line development is likely to replace manual methods of cell line development.

Cell line development and culturing is being rapidly adopted in areas of biological drug developments for various chronic diseases, regenerative medicines such as stem cells & cell-based therapies, recombinant protein, and other cellular entities for pharmaceuticals, diagnostics, and various other industries.

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Key Drivers and Opportunities of Global Cell Line Development Market

Rise in focus on research & development, owing to increase in prevalence of cancer and other chronic diseases is anticipated to drive the market. Several institutes, such as Cancer Research Institute, National Cancer Institute, Advanced Centre for Treatment, Research and Education in Cancer (Cancer Research Centre [ICRC]), and NCI Community Oncology Research Program (NCORP), are engaged in research & development for cancer diagnosis and treatment. Hence, the initiative of government and non-government organizations is likely boost the growth of the market.

Mammalian cell lines are widely used as production tools for various biologic drugs. Technological advancement in cell line development in mammalian cell culturing is likely to fuel the growth of the market. For instance, according to an article published in Pharmaceuticals (Basel), the U.S. Food and Drug Administered approved 15 novel recombinant protein therapeutics from 2005 to 2011 on an average.

Advances in bioinformatics and recombinant technologies have led to development of new cell lines for synthesis or production of essential peptides, enzymes, saccharides, and other molecules which are being used in pharmaceuticals and various other industries.

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North America to Capture Major Share of Global Cell Line Development Market

North America is expected to account for major share of the global cell line development market due to well-established health care infrastructure and rise in government initiatives. Furthermore, adoption of innovative technologies is likely to augment the market in the region.

The cell line development market in Asia Pacific is expected to grow at a rapid pace during the forecast period, owing to increasing risk of communicable diseases, cancer, and chronic & rare diseases and surge in geriatric population. For instance, according to an article published in BioMed Central Ltd, in 2018, 2.9 million cancer deaths occurred and 4.3 million new cancer cases were recorded in China.

Key Players Operating in Global Cell Line Development Market

The global cell line development market is highly concentrated due to the presence of key players. A large number of manufacturers hold major share in their respective regions. Key players engaged in adopting new strategies are likely to drive the global cell line development market. Key players are developing new, cost-effective biologic products. This is anticipated to augment the market.

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Major players operating in the global cell line development market are:

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Cell Line Development Market: Increase in Prevalence of Cancer and Other Chronic Diseases to Drive the Market - BioSpace

Stem Cell Therapy Market Is Expected To Reach USD455.61 Billion By 2027 At A CAGR Of 16 percent.

Maximize Market Research has published a report on theStem Cell Therapy Marketthat provides a detailed analysis for the forecast period of 2022 to 2027.

Stem Cell Therapy Market Scope:

The report provides comprehensive market insights for industry stakeholders, including an explanation of complicated market data in simple language, the industrys history and present situation, as well as expected market size and trends. The research investigates all industry categories, with an emphasis on key companies such as market leaders, followers, and new entrants. The paper includes a full PESTLE analysis for each country. A thorough picture of the competitive landscape of major competitors in the Stem Cell Therapy market by goods and services, revenue, financial situation, portfolio, growth plans, and geographical presence makes the study an investors guide.

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Stem Cell Therapy Market Overview:

Stem cells, which are the most important in the body, exist in both humans and animals. Stem cells, which may multiply and grow into almost any cell type in the body, are employed in surgery and medicine. There are two types of stem cells: adult stem cells and embryonic stem cells. Embryonic stem cells are stem cells derived from human embryos (ESCs). They are pluripotent, which means they can develop into practically any type of cell in the body. Regenerative medicine or cornerstone treatment are other terms for stem cell therapy. Regenerative medicines can restore cells and replace those that have been damaged or killed.

Mesenchymal stem cells may penetrate and integrate into different organs, heal cardiovascular, lung, and spinal cord injuries, and ameliorate the condition of autoimmune illnesses, liver disorders, and bone and cartilage diseases. Stem cells are an effective therapy option for infections induced by inflammation, immune system failure, or tissue degradation.

Stem Cell Therapy MarketDynamics:

The use of stem cells in regenerative medicine, notably in dermatology, is likely to drive significant growth in the global Stem Cell Therapy Market during the forecasted period. Additionally, increased oncology use, as a result of a large number of pipeline medications under development for the treatment of tumors or malignancies, would move the market ahead. The stem cell business is expected to flourish in the future as the number of regenerative medicine clinics increases. Moreover, the rising prevalence of chronic diseases has assisted the growth of the stem cell treatment sector.

Long work hours, a lack of physical activity, and unhealthy eating and drinking habits all lead to the development of chronic diseases and need stem cell therapy. Moreover, the growing death rate from chronic diseases throughout the world is expected to propel the worldwide Stem Cell Therapy Market ahead. Additionally, the growing popularity of personalized pharmaceuticals is driving the worldwide Stem Cell Therapy Market. Researchers have identified new procurement strategies that can be used to generate personalized pharmaceuticals.

Because stem cells are generated by killing human embryos, they raise several ethical concerns. Human embryos are recognized as potential life, and eliminating them, even if they can save a human life, is considered immoral. Concerns about using embryonic stem cells to develop stem cell therapies are restricting the global market growth.

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Stem Cell Therapy MarketRegional Insights:

The market for stem cell treatment was dominated by North America, Asia Pacific, and Europe. This geographical segments significant share of the stem cell therapy market can be attributed to increased public-private financing and research grants for producing safe and effective stem cell treatment products, as well as the growing number of clinical trials, as well as North Americas major share of the stem cell therapy market with increased sales of stem cell therapy.

Stem Cell Therapy MarketSegmentation:

By Treatment:

By Therapeutic Application:

By Cell Source:

By End users:

Stem Cell Therapy Market Key Competitors:

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Stem Cell Therapy Market Is Expected To Reach USD 455.61 Billion By 2027 At A CAGR Of 16 percent By Forecast 2027 Says Maximize Market Research (MMR)...

Global Surgical Mesh Market Is Estimated To Be Valued At US$ 1.29 Bn In 2022, And Is Forecast To Surpass US$ 2.2 Bn Valuation By The End Of 2032

Sales of surgical meshes are expected to account for more than 21 Mn units by 2032-end, owing to their increasing application in untapped markets, says a Fact.MR analyst.

Fact.MR A Market Research and Competitive Intelligence Provider: The global surgical mesh market is estimated to exceed a valuation of US$ 1.29 Bn in 2022, and expand at a significant CAGR of 5.5% by value over the assessment period (2022-2032).

The availability of surgical meshes in absorbable and non-absorbable forms has expanded their application for temporary as well as permanent reinforcement. In recent years, demand for surgical meshes has escalated in aiding breast reconstruction as they reduce the exposure risk of the implant. Increasing health literacy in North America and Europe will create ample opportunities for surgical mesh manufacturers over the coming years.

Sedentary lifestyle and increasing obesity among the population have resulted in several chronic health issues. The consequent weakening of the muscles extends space for organ prolapse and hernia. Putting these organs back in place by stitching the muscles together can result in muscle tearing and the recurrence of prolapse. However, reinforcing the weakened muscles with the help of a surgical mesh has shown to decrease recurrence and increase the longevity of the repair.

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Winning Strategy

To attract new customers, market players are focusing on portfolio enhancement. Robust investments in R&D are driving product innovation for key market players. Meshes inhibiting the growth of bacterial films and preventing tissue adhesions are luring new consumers. Collaboration of manufacturers with scientific personnel and operating surgeons have enabled bespoke designing of meshes to best fit patients needs.

Manufacturers are also aiming for portfolio expansion through acquisition and partnerships. Partnering with companies that offer a well-aligned portfolio has significantly increased consumer penetration for key manufacturers. However, augmenting relations with local players and operating surgeons will be a key determinant of the products commercial success.

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Scientific collaborations and robust R&D investments have also guided product innovation and became a common strategic approach adopted by leading surgical mesh manufacturing companies to upscale their market presence.

For instance:

Surgical Mesh Industry Research by Category

Surgical Mesh Market by Product Type:

Surgical Mesh Market by Nature:

Surgical Mesh Market by Surgical Access:

Surgical Mesh Market by Use Case:

Surgical Mesh Market by Raw Material:

Surgical Mesh Market by Region:

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Fact.MR, in its new offering, presents an unbiased analysis of the global surgical mesh market, presenting historical market data (2017-2021) and forecast statistics for the period of 2022-2032.

The study reveals essential insights on the basis of product type (synthetic, biosynthetic, biologic, hybrid/composite), nature of mesh (absorbable, non-absorbable, partially absorbable), surgical access (open surgery, laparoscopic surgery), use case (hernia repair, pelvic floor disorder treatment, breast reconstruction, others), and raw material (polypropylene, polyethylene terephthalate, expanded polytetrafluoroethylene, polyglycolic acid, decellularized dermis/ECM, others), across seven major regions (North America, Latin America, Europe, East Asia, South Asia & ASEAN, Oceania, MEA).

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Expert analysis, actionable insights, and strategic recommendations of the highly seasoned healthcare team at Fact.MR helps clients from across the globe with their unique business intelligence needs

With a repertoire of over thousand reports and 1 million-plus data points, the team has analysed the healthcare domain across 50+ countries for over a decade. The team provides unmatched end-to-end research and consulting services.

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Technical Advancements & Innovative Products Likely to Expand Application of Surgical Meshes in Untapped Domains, States Fact.MR - BioSpace

A paper recently published in the journal Biomaterials reviewed the new advances in three-dimensional bioprinting (3DBP) for regenerative therapy in different organ systems.

Study:Advances in 3D bioprinting of tissues/organs for regenerative medicine and in-vitro models. Image Credit:luchschenF/Shutterstock.com

Organ/tissue shortage has emerged as a significant challenge in the medical field due to patient immune rejections and donor scarcity. Moreover, mimicking or predicting the human disease condition in the animal models is difficult during preclinical trials owing to the differences in the disease phenotype between animals and humans.

3DBP has gained significant attention as a highly-efficient multidisciplinary technology to fabricate 3D biological tissue with complex composition and architecture. This technology allows precise assembly and deposition of biomaterials with donor/patients cells, leading to the successful fabrication of organ/tissue-like structures, preclinical implants, and in vitro models.

In this study, researchers reviewed the 3DBP strategies currently used for regenerative therapy in eight organ systems, including urinary, respiratory, gastrointestinal, exocrine and endocrine, integumentary, skeletal, cardiovascular, and nervous systems. Researchers also focused on the application of 3DBP to fabricate in vitro models. The concept of in situ 3DBP was discussed.

In this extensively used low-cost bioprinting method, rotating screw gear or pressurized air is used without or with temperature to extrude a continuous stream of thermoplastic or semisolid material. Different materials can be printed at a high fabrication speed using this technology. However, low cell viability and the need for post-processing are the major drawbacks of extrusion bioprinting.

In this method, liquid drops are ejected on a substrate by acoustic or thermal forces. High fabrication speed, small droplet volume, and interconnected micro-porosity gradient in the fabricated 3D structures are the main advantages of this technique. However, limited printed materials and clogging are the biggest drawbacks of inkjet bioprinting.

A laser is used to induce the forward transfer of biomaterials on a solid surface in the laser-assisted bioprinting method. High cell viability and nozzle-free noncontact process are the biggest advantages of laser-assisted bioprinting, while metallic particle contamination and the time-consuming nature of the printing process are the major disadvantages.

Several studies were performed involving the development of neuronal tissues using the 3DBP method. The pressure extrusion/syringe extrusion (PE/SE) bioprinting technique was used for central nervous tissue (CNS) tissue replacement. The layered porous structure was fabricated using glial cells derived using human induced pluripotent stem cell (iPSC) and a novel bioink based on agarose, alginate, and carboxymethyl chitosan (CMC) formed synaptic networks and displayed a bicuculline-induced enhanced calcium response.

Similarly, stereolithography (SLA) was used to fabricate a 3D scaffold for CNS and the viability of the scaffold was evaluated for regenerative medicine application. Layered linear microchannels were printed using poly(ethylene glycol) diacrylate-gelatin methacrylate (PEGDA-GelMA) and rat E14 neural progenitor cells (NPCs). The 3D scaffold restored the synaptic contacts and significantly improved the functional outcomes. Cyclohexane was used to bond polystyrene fibers to matrix bundle terminals during crosslinking.

Multiphoton excited 3-dimensional printing (MPE-3DP) was employed for the regeneration of myocardial tissue. A layer-by-layer structure was fabricated using GelMA/ sodium 4-[2-(4-morpholino)benzoyl-2-dimethylamino]-butylbenzenesulfonate (MBS) and human hciPSC-derived cardiomyocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs). The crosslinking was performed by photoactivation. The structure promoted electromechanical coupling and improved cell proliferation, vascularity, and cardiac function.

Fused deposition modeling (FDM) and PE/SE bioprinting method were used for complex tissue and organ regeneration. A micro-fluid network heart shape structure was fabricated using polyvinyl alcohol (PVA), agarose, sodium alginate, and platelet-rich plasma and rat H9c2 cells and human umbilical vein endothelial cells (HUVECs). 2% calcium dichloride was used during the crosslinking mechanism. The fabricated structure possessed a valentine heart with hollow mechanical properties and a self-defined height.

SE printing was utilized to fabricate a capillary-like network using collagen type1/ xanthan gum and human fibroblasts and ECs for applications in blood vessels. The fabricated network possessed endothelial networks and sprouting between the fibroblast layers.

Bone, cartilage, and skeletal muscle tissue can be repaired and regenerated using the 3DBP technique. For instance, FDM printing was used to print multifunctional therapeutic scaffolds for the treatment of bone. Filopodial projections were fabricated using polylactic acid (PLA) platform loaded with hyaluronic acid (HA)/ iron oxide nanoparticles (IONS)/ minocycline and human MG-63 and human bone marrow stromal cells (hBMSCs), which improved the osteogenic stimulation of the IONS and HA.

PE/SE method was used to fabricate disks and cuboid-shaped scaffolds using - tricalcium phosphate (TCP) microgel and human fetal osteoblast (hFOB) and bone marrow-derived mesenchymal stem cell (BM-MSC) for bone repair, multicellular delivery, and disease model. The fabricated structures promoted osteogenesis.

PE/SE bioprinting was also utilized to fabricate complex porous layered cartilage-like structures using alginate/gelatin/HA, rat bone marrow mesenchymal stem cells (BMSCs), and cow cardiac progenitor cells (CPCs) for hyaline cartilage regeneration. The CPCs upregulated gene expression of proteoglycan 4 (PRG4), SRY-box transcription factor 9 (SOX9), and collagen II.

PE/SE printing was also used to fabricate multinucleated, highly-aligned myotube structures using polyurethane (PU), poly(-caprolactone) (PCL), and mouse C2C12 myoblasts and NIH/3T3 fibroblasts for in-situ expansion and differentiation of skeletal muscle tendon. The fabricated constructs demonstrated more than 80% cell viability with initial tissue differentiation and development.

SLA bioprinting technique was used to fabricate bi-layered epidermis-like structure using collagen type I, mouse NIH 3T3 fibroblast cells, and human keratinocyte cells for tissue model and engineering. The fabricated constructs effectively imitated the tissue functions.

Similarly, PE was employed to fabricate microporous structures using human amniotic mesenchymal stem cells (AFSCs) and heparin-HA-PEGDA for wound healing. The construct improved the wound closure and reepithelialization, increased extracellular matrix synthesis and vascularization, and prolonged the cell paracrine activity.

PE technique was utilized to prepare a multilayered cornea-like structure using human keratocytes and methacrylated collagen (ColMA)-alginate. The cell viability of the keratocytes decreased from 90% to 83% after printing.

PE/SE bioprinting was utilized to bioprint multilayered liver-like structures using GeIMA and human HepG2/C3A for liver tissue engineering. Similarly, hepatocytes were also bioprinted to fabricate multiple organ precursors with branching vasculature. A small intestine model with improved intestinal function and high cell proliferation was fabricated using caco-2 cell-loaded polyethylene vinyl acetate (PEVA) scaffold.

Spheroids of mesenchymal stem cells (MSCs) and chondrocytes and lung endothelial cells were utilized to fabricate scaffold-free tracheal transplant. After implantation in the rat model, the matured spheroids displayed excellent vasculogenesis, chondrogenesis, and mechanical strength. FDM technique was used to fabricate a glomerular structure for kidneys using human iPSCs and hydrogel and a hollow porous network using poly(lactic-co-glycolic acid (PLGA)/PCL/tumor-associated endothelial cells (TECs) for the urethra.

In in-situ bioprinting, the tissue is directly printed on the specific defect or wound site in the body for regenerative and reparative therapy. This method provides a well-defined structure and reduces the gap between host-implant interfaces. In-situ bioprinting is better than in vitro bioprinting techniques as the patients body, as a natural bioreactor, provides a natural microenvironment.

Several studies have evaluated this technique for tissue regeneration. For instance, PE/SE method was used for skin tissue regeneration in pigs and mice using fibrin/collagen/HA and human fibroblast cells. Skin-laden sheets of consistent composition, thickness, and width were formed upon rapid crosslinking of biomaterial. PE/SE technique was also used for neural tissue regeneration in mice using agarose/CMC/alginate and human iPSCs.

In vitro models provide significant assistance in understanding the mechanism of therapeutics and disease pathophysiology. Recently, in vitro models of human tissues and organs were engineered using 3DBP technology for safety assessment and drug testing.

In the 3DBP of organs and tissues, biomaterials play a crucial role in maintaining cellular viability, providing support, and long-term acceptance. Specifically, bioinks must possess unique properties, such as cell growth promotion and structural stability, that can be optimized for clinical use. Additionally, bioinks must be compatible with printers for high-precision rapid prototyping.

Bioinks fulfilling all of these requirements are yet to be identified. Moreover, managing the time during the bioprinting of the constructs is another major challenge, as the time required to fabricate them is often more than the survival time of cells. A bioreactor platform that supports organoid growth and provides time for tissue remodeling can be used to overcome this challenge. Ethical challenges and issues are also a hurdle since fabricating internal tissues/organs can lead to liability and biosafety concerns.

In the future, 3DBP can provide novel solutions to engineer organs/tissues and revolutionize modern healthcare and medicine if these challenges can be addressed.

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Jain, P., Kathuria, H., Dubey, N. Advances in 3D bioprinting of tissues/organs for regenerative medicine and in-vitro models. Biomaterials 2022. https://www.sciencedirect.com/science/article/abs/pii/S0142961222002794?via%3Dihub

Disclaimer: The views expressed here are those of the author expressed in their private capacity and do not necessarily represent the views of AZoM.com Limited T/A AZoNetwork the owner and operator of this website. This disclaimer forms part of the Terms and conditions of use of this website.

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What New Advances are there in 3D Bioprinting Tissues? - AZoM

Cells in the body have specific purposes, but stem cells are cells that do not yet have a specific role and can become almost any cell that is required.

Stem cells are undifferentiated cells that can turn into specific cells, as the body needs them.

Scientists and doctors are interested in stem cells as they help to explain how some functions of the body work, and how they sometimes go wrong.

Stem cells also show promise for treating some diseases that currently have no cure.

Stem cells originate from two main sources: adult body tissues and embryos. Scientists are also working on ways to develop stem cells from other cells, using genetic reprogramming techniques.

A persons body contains stem cells throughout their life. The body can use these stem cells whenever it needs them.

Also called tissue-specific or somatic stem cells, adult stem cells exist throughout the body from the time an embryo develops.

The cells are in a non-specific state, but they are more specialized than embryonic stem cells. They remain in this state until the body needs them for a specific purpose, say, as skin or muscle cells.

Day-to-day living means the body is constantly renewing its tissues. In some parts of the body, such as the gut and bone marrow, stem cells regularly divide to produce new body tissues for maintenance and repair.

Stem cells are present inside different types of tissue. Scientists have found stem cells in tissues, including:

However, stem cells can be difficult to find. They can stay non-dividing and non-specific for years until the body summons them to repair or grow new tissue.

Adult stem cells can divide or self-renew indefinitely. This means they can generate various cell types from the originating organ or even regenerate the original organ, entirely.

This division and regeneration are how a skin wound heals, or how an organ such as the liver, for example, can repair itself after damage.

In the past, scientists believed adult stem cells could only differentiate based on their tissue of origin. However, some evidence now suggests that they can differentiate to become other cell types, as well.

From the very earliest stage of pregnancy, after the sperm fertilizes the egg, an embryo forms.

Around 35 days after a sperm fertilizes an egg, the embryo takes the form of a blastocyst or ball of cells.

The blastocyst contains stem cells and will later implant in the womb. Embryonic stem cells come from a blastocyst that is 45 days old.

When scientists take stem cells from embryos, these are usually extra embryos that result from in vitro fertilization (IVF).

In IVF clinics, the doctors fertilize several eggs in a test tube, to ensure that at least one survives. They will then implant a limited number of eggs to start a pregnancy.

When a sperm fertilizes an egg, these cells combine to form a single cell called a zygote.

This single-celled zygote then starts to divide, forming 2, 4, 8, 16 cells, and so on. Now it is an embryo.

Soon, and before the embryo implants in the uterus, this mass of around 150200 cells is the blastocyst. The blastocyst consists of two parts:

The inner cell mass is where embryonic stem cells are found. Scientists call these totipotent cells. The term totipotent refer to the fact that they have total potential to develop into any cell in the body.

With the right stimulation, the cells can become blood cells, skin cells, and all the other cell types that a body needs.

In early pregnancy, the blastocyst stage continues for about 5 days before the embryo implants in the uterus, or womb. At this stage, stem cells begin to differentiate.

Embryonic stem cells can differentiate into more cell types than adult stem cells.

MSCs come from the connective tissue or stroma that surrounds the bodys organs and other tissues.

Scientists have used MSCs to create new body tissues, such as bone, cartilage, and fat cells. They may one day play a role in solving a wide range of health problems.

Scientists create these in a lab, using skin cells and other tissue-specific cells. These cells behave in a similar way to embryonic stem cells, so they could be useful for developing a range of therapies.

However, more research and development is necessary.

To grow stem cells, scientists first extract samples from adult tissue or an embryo. They then place these cells in a controlled culture where they will divide and reproduce but not specialize further.

Stem cells that are dividing and reproducing in a controlled culture are called a stem-cell line.

Researchers manage and share stem-cell lines for different purposes. They can stimulate the stem cells to specialize in a particular way. This process is known as directed differentiation.

Until now, it has been easier to grow large numbers of embryonic stem cells than adult stem cells. However, scientists are making progress with both cell types.

Researchers categorize stem cells, according to their potential to differentiate into other types of cells.

Embryonic stem cells are the most potent, as their job is to become every type of cell in the body.

The full classification includes:

Totipotent: These stem cells can differentiate into all possible cell types. The first few cells that appear as the zygote starts to divide are totipotent.

Pluripotent: These cells can turn into almost any cell. Cells from the early embryo are pluripotent.

Multipotent: These cells can differentiate into a closely related family of cells. Adult hematopoietic stem cells, for example, can become red and white blood cells or platelets.

Oligopotent: These can differentiate into a few different cell types. Adult lymphoid or myeloid stem cells can do this.

Unipotent: These can only produce cells of one kind, which is their own type. However, they are still stem cells because they can renew themselves. Examples include adult muscle stem cells.

Embryonic stem cells are considered pluripotent instead of totipotent because they cannot become part of the extra-embryonic membranes or the placenta.

Stem cells themselves do not serve any single purpose but are important for several reasons.

First, with the right stimulation, many stem cells can take on the role of any type of cell, and they can regenerate damaged tissue, under the right conditions.

This potential could save lives or repair wounds and tissue damage in people after an illness or injury. Scientists see many possible uses for stem cells.

Tissue regeneration is probably the most important use of stem cells.

Until now, a person who needed a new kidney, for example, had to wait for a donor and then undergo a transplant.

There is a shortage of donor organs but, by instructing stem cells to differentiate in a certain way, scientists could use them to grow a specific tissue type or organ.

As an example, doctors have already used stem cells from just beneath the skins surface to make new skin tissue. They can then repair a severe burn or another injury by grafting this tissue onto the damaged skin, and new skin will grow back.

In 2013, a team of researchers from Massachusetts General Hospital reported in PNAS Early Edition that they had created blood vessels in laboratory mice, using human stem cells.

Within 2 weeks of implanting the stem cells, networks of blood-perfused vessels had formed. The quality of these new blood vessels was as good as the nearby natural ones.

The authors hoped that this type of technique could eventually help to treat people with cardiovascular and vascular diseases.

Doctors may one day be able to use replacement cells and tissues to treat brain diseases, such as Parkinsons and Alzheimers.

In Parkinsons, for example, damage to brain cells leads to uncontrolled muscle movements. Scientists could use stem cells to replenish the damaged brain tissue. This could bring back the specialized brain cells that stop the uncontrolled muscle movements.

Researchers have already tried differentiating embryonic stem cells into these types of cells, so treatments are promising.

Scientists hope one day to be able to develop healthy heart cells in a laboratory that they can transplant into people with heart disease.

These new cells could repair heart damage by repopulating the heart with healthy tissue.

Similarly, people with type I diabetes could receive pancreatic cells to replace the insulin-producing cells that their own immune systems have lost or destroyed.

The only current therapy is a pancreatic transplant, and very few pancreases are available for transplant.

Doctors now routinely use adult hematopoietic stem cells to treat diseases, such as leukemia, sickle cell anemia, and other immunodeficiency problems.

Hematopoietic stem cells occur in blood and bone marrow and can produce all blood cell types, including red blood cells that carry oxygen and white blood cells that fight disease.

People can donate stem cells to help a loved one, or possibly for their own use in the future.

Donations can come from the following sources:

Bone marrow: These cells are taken under a general anesthetic, usually from the hip or pelvic bone. Technicians then isolate the stem cells from the bone marrow for storage or donation.

Peripheral stem cells: A person receives several injections that cause their bone marrow to release stem cells into the blood. Next, blood is removed from the body, a machine separates out the stem cells, and doctors return the blood to the body.

Umbilical cord blood: Stem cells can be harvested from the umbilical cord after delivery, with no harm to the baby. Some people donate the cord blood, and others store it.

This harvesting of stem cells can be expensive, but the advantages for future needs include:

Stem cells are useful not only as potential therapies but also for research purposes.

For example, scientists have found that switching a particular gene on or off can cause it to differentiate. Knowing this is helping them to investigate which genes and mutations cause which effects.

Armed with this knowledge, they may be able to discover what causes a wide range of illnesses and conditions, some of which do not yet have a cure.

Abnormal cell division and differentiation are responsible for conditions that include cancer and congenital disabilities that stem from birth. Knowing what causes the cells to divide in the wrong way could lead to a cure.

Stem cells can also help in the development of new drugs. Instead of testing drugs on human volunteers, scientists can assess how a drug affects normal, healthy tissue by testing it on tissue grown from stem cells.

Watch the video to find out more about stem cells.

There has been some controversy about stem cell research. This mainly relates to work on embryonic stem cells.

The argument against using embryonic stem cells is that it destroys a human blastocyst, and the fertilized egg cannot develop into a person.

Nowadays, researchers are looking for ways to create or use stem cells that do not involve embryos.

Stem cell research often involves inserting human cells into animals, such as mice or rats. Some people argue that this could create an organism that is part human.

In some countries, it is illegal to produce embryonic stem cell lines. In the United States, scientists can create or work with embryonic stem cell lines, but it is illegal to use federal funds to research stem cell lines that were created after August 2001.

Some people are already offering stem-cells therapies for a range of purposes, such as anti-aging treatments.

However, most of these uses do not have approval from the U.S. Food and Drug Administration (FDA). Some of them may be illegal, and some can be dangerous.

Anyone who is considering stem-cell treatment should check with the provider or with the FDA that the product has approval, and that it was made in a way that meets with FDA standards for safety and effectiveness.

More here:
Stem cells: Sources, types, and uses - Medical News Today

Stem cell technology will transform medical practice. While stem cell research has already elucidated many basic disease mechanisms, the promise of stem cellbased therapies remains largely unrealized. In this review, we begin with an overview of different stem cell types. Next, we review the progress in using stem cells for regenerative therapy. Last, we discuss the risks associated with stem cellbased therapies.

There are three major types of stem cells as follows: adult stem cells (also called tissue-specific stem cells), embryonic stem (ES) cells, and induced pluripotent stem (iPS) cells.

A majority of adult stem cells are lineage-restricted cells that often reside within niches of their tissue of origin. Adult stem cells are characterized by their capacity for self-renewal and differentiation into tissue-specific cell types. Many adult tissues contain stem cells including skin, muscle, intestine, and bone marrow (Gan et al, 1997; Artlett et al, 1998; Matsuoka et al, 2001; Coulombel, 2004; Humphries et al, 2011). However, it remains unclear whether all adult organs contain stem cells. Adult stem cells are quiescent but can be induced to replicate and differentiate after tissue injury to replace cells that have died. The process by which this occurs is poorly understood. Importantly, adult stem cells are exquisitely tissue-specific in that they can only differentiate into the mature cell type of the organ within which they reside (Rinkevich et al, 2011).

Thus far, there are few accepted adult stem cellbased therapies. Hematopoietic stem cells (HSCs) can be used after myeloablation to repopulate the bone marrow in patients with hematologic disorders, potentially curing the underlying disorder (Meletis and Terpos, 2009; Terwey et al, 2009; Casper et al, 2010; Hill and Copelan, 2010; Hoff and Bruch-Gerharz, 2010; de Witte et al, 2010). HSCs are found most abundantly in the bone marrow, but can also be harvested at birth from umbilical cord blood (Broxmeyer et al, 1989). Similar to the HSCs harvested from bone marrow, cord blood stem cells are tissue-specific and can only be used to reconstitute the hematopoietic system (Forraz et al, 2002; McGuckin et al, 2003; McGuckin and Forraz, 2008). In addition to HSCs, limbal stem cells have been used for corneal replacement (Rama et al, 2010).

Mesenchymal stem cells (MSCs) are a subset of adult stem cells that may be particularly useful for stem cellbased therapies for three reasons. First, MSCs have been isolated from a variety of mesenchymal tissues, including bone marrow, muscle, circulating blood, blood vessels, and fat, thus making them abundant and readily available (Deans and Moseley, 2000; Zhang et al, 2009; Lue et al, 2010; Portmann-Lanz et al, 2010). Second, MSCs can differentiate into a wide array of cell types, including osteoblasts, chondrocytes, and adipocytes (Pittenger et al, 1999). This suggests that MSCs may have broader therapeutic applications compared to other adult stem cells. Third, MSCs exert potent paracrine effects enhancing the ability of injured tissue to repair itself. In fact, animal studies suggest that this may be the predominant mechanism by which MSCs promote tissue repair. The paracrine effects of MSC-based therapy have been shown to aid in angiogenic, antiapoptotic, and immunomodulatory processes. For instance, MSCs in culture secrete hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF) (Nagaya et al, 2005). In a rat model of myocardial ischemia, injection of human bone marrow-derived stem cells upregulated cardiac expression of VEGF, HGF, bFGF, angiopoietin-1 and angiopoietin-2, and PDGF (Yoon et al, 2005). In swine, injection of bone marrow-derived mononuclear cells into ischemic myocardium was shown to increase the expression of VEGF, enhance angiogenesis, and improve cardiac performance (Tse et al, 2007). Bone marrow-derived stem cells have also been used in a number of small clinical trials with conflicting results. In the largest of these trials (REPAIR-AMI), 204 patients with acute myocardial infarction were randomized to receive bone marrow-derived progenitor cells vs placebo 37 days after reperfusion. After 4 months, the patients that were infused with stem cells showed improvement in left ventricular function compared to control patients. At 1 year, the combined endpoint of recurrent ischemia, revascularization, or death was decreased in the group treated with stem cells (Schachinger et al, 2006).

Embryonic stem cells are derived from the inner cell mass of the developing embryo during the blastocyst stage (Thomson et al, 1998). In contrast to adult stem cells, ES cells are pluripotent and can theoretically give rise to any cell type if exposed to the proper stimuli. Thus, ES cells possess a greater therapeutic potential than adult stem cells. However, four major obstacles exist to implementing ES cells therapeutically. First, directing ES cells to differentiate into a particular cell type has proven to be challenging. Second, ES cells can potentially transform into cancerous tissue. Third, after transplantation, immunological mismatch can occur resulting in host rejection. Fourth, harvesting cells from a potentially viable embryo raises ethical concerns. At the time of this publication, there are only two ongoing clinical trials utilizing human ES-derived cells. One trial is a safety study for the use of human ES-derived oligodendrocyte precursors in patients with paraplegia (Genron based in Menlo Park, California). The other is using human ES-derived retinal pigmented epithelial cells to treat blindness resulting from macular degeneration (Advanced Cell Technology, Santa Monica, CA, USA).

In stem cell research, the most exciting recent advancement has been the development of iPS cell technology. In 2006, the laboratory of Shinya Yamanaka at the Gladstone Institute was the first to reprogram adult mouse fibroblasts into an embryonic-like cell, or iPS cell, by overexpression of four transcription factors, Oct3/4, Sox2, c-Myc, and Klf4 under ES cell culture conditions (Takahashi and Yamanaka, 2006). Yamakana's pioneering work in cellular reprogramming using adult mouse cells set the foundation for the successful creation of iPS cells from adult human cells by both his team (Takahashi et al, 2007) and a group led by James Thomson at the University of Wisconsin (Yu et al, 2007). These initial proof of concept studies were expanded upon by leading scientists such as George Daley, who created the first library of disease-specific iPS cell lines (Park et al, 2008). These seminal discoveries in the cellular reprogramming of adult cells invigorated the stem cell field and created a niche for a new avenue of stem cell research based on iPS cells and their derivatives. Since the first publication on cellular reprogramming in 2006, there has been an exponential growth in the number of publications on iPS cells.

Similar to ES cells, iPS cells are pluripotent and, thus, have tremendous therapeutic potential. As of yet, there are no clinical trials using iPS cells. However, iPS cells are already powerful tools for modeling disease processes. Prior to iPS cell technology, in vitro cell culture disease models were limited to those cell types that could be harvested from the patient without harm usually dermal fibroblasts from skin biopsies. However, mature dermal fibroblasts alone cannot recapitulate complicated disease processes involving multiple cell types. Using iPS technology, dermal fibroblasts can be de-differentiated into iPS cells. Subsequently, the iPS cells can be directed to differentiate into the cell type most beneficial for modeling a particular disease process. Advances in the production of iPS cells have found that the earliest pluripotent stage of the derivation process can be eliminated under certain circumstances. For instance, dermal fibroblasts have been directly differentiated into dopaminergic neurons by viral co-transduction of forebrain transcriptional regulators (Brn2, Myt1l, Zic1, Olig2, and Ascl1) in the presence of media containing neuronal survival factors [brain-derived neurotrophic factor, neurotrophin-3 (NT3), and glial-conditioned media] (Qiang et al, 2011). Additionally, dermal fibroblasts have been directly differentiated into cardiomyocyte-like cells using the transcription factors Gata4, Mef2c, and Tb5 (Ieda et al, 2010). Regardless of the derivation process, once the cell type of interest is generated, the phenotype central to the disease process can be readily studied. In addition, compounds can be screened for therapeutic benefit and environmental toxins can be screened as potential contributors to the disease. Thus far, iPS cells have generated valuable in vitro models for many neurodegenerative (including Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis), hematologic (including Fanconi's anemia and dyskeratosis congenital), and cardiac disorders (most notably the long QT syndrome) (Park et al, 2008). iPS cells from patients with the long QT syndrome are particularly interesting as they may provide an excellent platform for rapidly screening drugs for a common, lethal side effect (Zwi et al, 2009; Malan et al, 2011; Tiscornia et al, 2011). The development of patient-specific iPS cells for in vitro disease modeling will determine the potential for these cells to differentiate into desired cell lineages, serve as models for investigating the mechanisms underlying disease pathophysiology, and serve as tools for future preclinical drug screening and toxicology studies.

Despite substantial improvements in therapy, cardiovascular disease remains the leading cause of death in the industrialized world. Therefore, there is a particular interest in cardiovascular regenerative therapies. The potential of diverse progenitor cells to repair damaged heart tissue includes replacement (tissue transplant), restoration (activation of resident cardiac progenitor cells, paracrine effects), and regeneration (stem cell engraftment forming new myocytes) (Codina et al, 2010). It is unclear whether the heart contains resident stem cells. However, experiments show that bone marrow mononuclear cells (BMCs) can repair myocardial damage, reduce left ventricular remodeling, and improve heart function by myocardial regeneration (Hakuno et al, 2002; Amado et al, 2005; Dai et al, 2005; Schneider et al, 2008). The regenerative capacity of human heart tissue was further supported by the detection of the renewal of human cardiomyocytes (1% annually at the age of 25) by analysis of carbon-14 integration into human cardiomyocyte DNA (Bergmann et al, 2009). It is not clear whether cardiomyocyte renewal is derived from resident adult stem cells, cardiomyocyte duplication, or homing of non-myocardial progenitor cells. Bone marrow cells home to the injured myocardium as shown by Y chromosome-positive BMCs in female recipients (Deb et al, 2003). On the basis of these promising results, clinical trials in patients with ischemic heart disease have been initiated primarily using bone marrow-derived cells. However, these small trials have shown controversial results. This is likely due to a lack of standardization for cell harvesting and delivery procedures. This highlights the need for a better understanding of the basic mechanisms underlying stem cell isolation and homing prior to clinical implementation.

Although stem cells have the capacity to differentiate into neurons, oligodendrocytes, and astrocytes, novel clinical stem cellbased therapies for central and peripheral nervous system diseases have yet to be realized. It is widely hoped that transplantation of stem cells will provide effective therapy for Parkinson's disease, Alzheimer's disease, Huntington's Disease, amyloid lateral sclerosis, spinal cord injury, and stroke. Several encouraging animal studies have shown that stem cells can rescue some degree of neurological function after injury (Daniela et al, 2007; Hu et al, 2010; Shimada and Spees, 2011). Currently, a number of clinical trials have been performed and are ongoing.

Dental stem cells could potentially repair damaged tooth tissues such as dentin, periodontal ligament, and dental pulp (Gronthos et al, 2002; Ohazama et al, 2004; Jo et al, 2007; Ikeda et al, 2009; Balic et al, 2010; Volponi et al, 2010). Moreover, as the behavior of dental stem cells is similar to MSCs, dental stem cells could also be used to facilitate the repair of non-dental tissues such as bone and nerves (Huang et al, 2009; Takahashi et al, 2010). Several populations of cells with stem cell properties have been isolated from different parts of the tooth. These include cells from the pulp of both exfoliated (children's) and adult teeth, the periodontal ligament that links the tooth root with the bone, the tips of developing roots, and the tissue that surrounds the unerupted tooth (dental follicle) (Bluteau et al, 2008). These cells probably share a common lineage from neural crest cells, and all have generic mesenchymal stem cell-like properties, including expression of marker genes and differentiation into mesenchymal cells in vitro and in vivo (Bluteau et al, 2008). different cell populations do, however, differ in certain aspects of their growth rate in culture, marker gene expression, and cell differentiation. However, the extent to which these differences can be attributed to tissue of origin, function, or culture conditions remains unclear.

There are several issues determining the long-term outcome of stem cellbased therapies, including improvements in the survival, engraftment, proliferation, and regeneration of transplanted cells. The genomic and epigenetic integrity of cell lines that have been manipulated in vitro prior to transplantation play a pivotal role in the survival and clinical benefit of stem cell therapy. Although stem cells possess extensive replicative capacity, immune rejection of donor cells by the host immune system post-transplantation is a primary concern (Negro et al, 2012). Recent studies have shown that the majority of donor cell death occurs in the first hours to days after transplantation, which limits the efficacy and therapeutic potential of stem cellbased therapies (Robey et al, 2008).

Although mouse and human ES cells have traditionally been classified as being immune privileged, a recent study used in vivo, whole-animal, live cell-tracing techniques to demonstrate that human ES cells are rapidly rejected following transplantation into immunocompetent mice (Swijnenburg et al, 2008). Treatment of ES cell-derived vascular progenitor cells with inter-feron (to upregulate major histocompatibility complex (MHC) class I expression) or in vivo ablation of natural killer (NK) cells led to enhanced progenitor cell survival after transplantation into a syngeneic murine ischemic hindlimb model. This suggests that MHC class I-dependent, NK cell-mediated elimination is a major determinant of graft survivability (Ma et al, 2010). Given the risk of rejection, it is likely that initial therapeutic attempts using either ES or iPS cells will require adjunctive immunosuppressive therapy. Immunosuppressive therapy, however, puts the patient at risk of infection as well as drug-specific adverse reactions. As such, determining the mechanisms regulating donor graft tolerance by the host will be crucial for advancing the clinical application of stem cellbased therapies.

An alternative strategy to avoid immune rejection could employ so-called gene editing. Using this technique, the stem cell genome is manipulated ex vivo to correct the underlying genetic defect prior to transplantation. Additionally, stem cell immunologic markers could be manipulated to evade the host immune response. Two recent papers offer alternative methods for gene editing. Soldner et al (2011) used zinc finger nuclease to correct the genetic defect in iPS cells from patients with Parkinson's disease because of a mutation in the -Synuclein (-SYN) gene. Liu et al (2011) used helper-dependent adenoviral vectors (HDAdV) to correct the mutation in the Lamin A (LMNA) gene in iPS cells derived from patients with HutchinsonGilford Progeria (HGP), a syndrome of premature aging. Cells from patients with HGP have dysmorphic nuclei and increased levels of progerin protein. The cellular phenotype is especially pronounced in mature, differentiated cells. Using highly efficient helper-dependent adenoviral vectors containing wild-type sequences, they were able to use homologous recombination to correct two different Lamin A mutations. After genetic correction, the diseased cellular phenotype was reversed even after differentiation into mature smooth muscle cells. In addition to the potential therapeutic benefit, gene editing could generate appropriate controls for in vitro studies.

Finally, there are multiple safety and toxicity concerns regarding the transplantation, engraftment, and long-term survival of stem cells. Donor stem cells that manage to escape immune rejection may later become oncogenic because of their unlimited capacity to replicate (Amariglio et al, 2009). Thus, ES and iPS cells may need to be directed into a more mature cell type prior to transplantation to minimize this risk. Additionally, generation of ES and iPS cells harboring an inducible kill-switch may prevent uncontrolled growth of these cells and/or their derivatives. In two ongoing human trials with ES cells, both companies have provided evidence from animal studies that these cells will not form teratomas. However, this issue has not been thoroughly examined, and enrolled patients will need to be monitored closely for this potentially lethal side effect.

In addition to the previously mentioned technical issues, the use of ES cells raises social and ethical concerns. In the past, these concerns have limited federal funding and thwarted the progress of this very important research. Because funding limitations may be reinstituted in the future, ES cell technology is being less aggressively pursued and young researchers are shying away from the field.

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The benefits and risks of stem cell technology - PMC

While historically lacking in foreign investments, Japans biotech scene is thriving with global investors showing increasing interest. Here are five of the hottest Japanese private companies innovating in the healthcare space.

Japan boasts one of the highest life expectancies in the world, and, faced with a rapidly aging population, is witnessing a growing burden of chronic conditions including cardiovascular disease and type 2 diabetes. For this reason, the Japanese healthcare authorities are encouraging research into the treatment and prevention of these diseases, in addition to promoting the potential of regenerative medicine.

In addition to having a roster of healthcare giants including Takeda, Astellas Pharma and Eisai, Japan is also an Asian hotspot for biotech companies. Upcoming startups have historically been limited in foreign funding and reliant on local venture capital players such as Nippon Venture Capital, Shinsei Capital Partners, and the University of Tokyo Edge Capital Partners.

In 2021, however, the amount of foreign investment flowing into the Japanese biotech space rose to $98 million, almost triple the haul of previous years. The most prominent global backers included Newton Biocapital, F-Prime Capital, and SoftBank Group. This trend arose as the COVID-19 pandemic triggered a wave of investor enthusiasm in biotechnology around the world.

With the help of local experts, weve listed five of the hottest private biotech companies in Japan. These firms, shown in alphabetical order, have raised large funding rounds in the last two years and are developing innovative treatments for a range of conditions including cancer, cardiovascular disease and inflammatory disorders.

Source: Shutterstock

Founded: 2017

Headquarters: Fujisawa

Chordia Therapeutics derives its name from the English term chord referring to a collection of musical notes normally played in harmony. In a similar way, the company aims to work in harmony with stakeholders and collaborators to develop first-in-class small molecule treatments for cancer.

Chordias lead program is a drug that disrupts the processing of RNA in tumor cells. In a healthy cell, RNA molecules are typically transcribed from a DNA template and spliced together to guide the production of new proteins. Some cancer cells accumulate mutations in the RNA splicing machinery and become vulnerable to Chordias drugs that interfere with this process.

Chordia raised $31 million (4 billion yen) in a Series C round in May 2022. The aim of the round was to push the companys lead drug through phase I testing and fund the preclinical development of the rest of its pipeline.

This month, the company announced interim results from the phase I trial of its lead candidate, with four of the recruited patients so far showing signs of responding to the treatment.

Founded: 2015

Headquarters: Tokyo

Heart failure occurs when the heart muscle is irreparably damaged and is unable to pump blood. While this deadly condition can be treated with a heart transplant, there is a general shortage of donors available, making a pressing need for alternatives.

In June 2021, the stem cell therapy developer Heartseed raised $36.5 million (4 billion yen) in a Series C round. The mission is to provide a regenerative route to saving the heart via stem cell therapy.

In the lab, Heartseed reprograms skin cells from the patient into a type of stem cell called induced pluripotent stem cells and grows these stem cells into heart muscle cells. The company then injects the muscle cells as a small cluster, or seed, into heart tissue to repair the muscle.

The proceedings from its Series C round will allow Heartseed to take its lead candidate into clinical development, including a phase I/II trial scheduled for later this year. Last year, Heartseed also licensed its treatment to Novo Nordisk in Denmark to co-develop the treatment outside of Japan.

Founded: 2018

Headquarters: Tokyo

LUCA Science hit the headlines in the last week for raising an impressive $30.3 million (3.86 billion yen) in a Series B round. The company is developing an unusual approach for treating a wide range of diseases: delivering a therapy based on mitochondria, the energy production plants in human cells.

One example where the technology could work well is in strokes and heart attacks, where blood flow is blocked to critical tissue in the brain and heart respectively. The reperfusion of blood to these tissues after the blockage can kill the tissue by damaging its mitochondria. Delivering healthy mitochondria could keep the tissue working properly and protect it from harm.

LUCA Science plans to use its recent Series B winnings to accelerate the preclinical development of its mitochondrial therapies and establish its manufacturing process. In May 2022, the firm also inked a collaboration deal with compatriot pharmaceutical company Kyowa Kirin Co., Ltd. to co-develop a mitochondrial therapy for rare genetic diseases.

Founded: 2016

Headquarters: Boston, U.S., and Tokyo

Modulus Discovery is a preclinical-stage drug discovery specialist. The company focuses on developing small molecule treatments for conditions such as cancer, inflammatory disorders and rare genetic conditions.

The firm uses a mixture of strategies to speed up the drug discovery process. These include simulating target proteins using a supercomputer; structural protein biology; forming collaborations such as with the peptide drug expert PeptiDream; and tapping into global networks for biological expertise. Modulus most advanced drug program is in late-stage preclinical testing for the treatment of chronic inflammatory diseases.

In March 2022, Modulus bagged $20.4 million (2.34 billion yen) in a Series C round. The cash is earmarked to advance the companys R&D programs by expanding its infrastructure, collaborations and headcount.

Founded: 2015

Headquarters: Tokyo

The name Noile-Immune is derived from blending together the phrases no illness and no immunity, no life. This company is developing CAR-T cell therapies for the treatment of cancer, which traditionally consist of extracting the patients immune T cells, engineering them in the lab to hunt down cancer cells, and reinfusing them into the patient.

Unlike approved CAR-T cell therapies, which are limited to treating forms of blood cancer, Noile-Immune aims its therapies at treating solid tumors. The company does this by engineering immune T cells to produce proteins that cause immune cells to migrate into the tumor site.

Noile-Immune is testing its lead candidate in a phase I in patients with solid tumors. The firm is also co-developing therapies with partners including Takeda and the European cell therapy specialists Adaptimmune and Autolus. Additionally, Noile-Immune has an allogeneic version of its cell therapy in the pipeline where immune T cells are sourced from healthy donors rather than the patient.

To finance the clinical development of its lead candidate, Noile-Immune raised $21.8 million (2.38 billion yen) in a Series C round in early 2021. The company hit a setback in January 2022 when a collaboration deal fell through with the U.S. player Legend Biotech. Nonetheless, other external companies remain interested in Noile-Immunes offering, including Japan-based Daiichi Sankyo Company Ltd., which opted to assess Noile-Immunes technology in late 2021.

Cover image via Elena Resko.

Thanks to feedback from Shiohara Azusa, VC Investor at The University of Tokyo Edge Capital, and Hironoshin Nomura, Chief Financial Officer, Sosei Group Corporation.

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Japan's five hottest biotech companies in healthcare - Labiotech.eu

TAIPEI--(BUSINESS WIRE)--PharmaEssentia Corporation (TPEx:6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, today announced a series of data presentations will illustrate outcomes with ropeginterferon alfa-2b (marketed as BESREMi) among adults with polycythemia vera (PV) during the European Hematology Associations Hybrid Congress (EHA2022), June 9-17 in Vienna, Austria.

Ongoing evaluations of ropeginterferon alfa-2b expand the depth and duration of data on this innovative therapeutic supporting its ability to control the effects of polycythemia vera (PV), said Albert Qin, MD, PhD, Chief Medical Officer, PharmaEssentia. We believe these important new data offer greater clarity and confidence to physicians that this therapeutic tool represents an approach to effectively and durably treat PV.

Ropeginterferon alfa-2b presentations during EHA2022 will include:

The data presentation regarding the final results of studies leading to marketing authorization of BESREMi in Europe are a result of clinical development work of AOP Health, Vienna. PharmaEssentia has licensed ropeginterferon alfa-2b in Europe to AOP.

About Polycythemia Vera

Polycythemia Vera (PV) is a cancer originating from a disease-initiating stem cell in the bone marrow resulting in a chronic increase of red blood cells, white blood cells, and platelets. PV may result in cardiovascular complications such as thrombosis and embolism, and often transforms to secondary myelofibrosis or leukemia. While the molecular mechanism underlying PV is still subject of intense research, current results point to a set of acquired mutations, the most important being a mutant form of JAK2.1

About BESREMi (ropeginterferon alfa-2b)

BESREMi is an innovative monopegylated, long-acting interferon. With its unique pegylation technology, BESREMi has a long duration of activity in the body and is aimed to be administered once every two weeks (or every four weeks with hematological stability for at least one year), allowing flexible dosing that helps meet the individual needs of patients.

BESREMi has orphan drug designation for treatment of polycythemia vera (PV) in adults in the United States. The product was approved by the European Medicines Agency (EMA) in 2019, in the United States in 2021, and has recently received approval in Taiwan and South Korea. The drug candidate was invented by PharmaEssentia and is manufactured in the companys Taichung plant, which was cGMP certified by TFDA in 2017 and by EMA in January 2018. PharmaEssentia retains full global intellectual property rights for the product in all indications.

BESREMi was approved with a boxed warning for risk of serious disorders including aggravation of neuropsychiatric, autoimmune, ischemic and infectious disorders.

About PharmaEssentia

PharmaEssentia Corporation (TPEx: 6446), based in Taipei, Taiwan, is a rapidly growing biopharmaceutical innovator. Leveraging deep expertise and proven scientific principles, the company aims to deliver effective new biologics for challenging diseases in the areas of hematology and oncology, with one approved product and a diversifying pipeline. Founded in 2003 by a team of Taiwanese-American executives and renowned scientists from U.S. biotechnology and pharmaceutical companies, today the company is expanding its global presence with operations in the U.S., Japan, China, and Korea, along with a world-class biologics production facility in Taichung. For more information, visit our website.

1 Cerquozzi S, Tefferi A. Blast Transformation and Fibrotic Progression in Polycythemia Vera and Essential Thrombocythemia: A Literature Review of Incidence and Risk Factors. Blood Cancer Journal (2015) 5, e366; doi:10.1038/bcj.2015.95.

2022 PharmaEssentia Corporation. All rights reserved.

BESREMi and PharmaEssentia are registered trademarks of PharmaEssentia Corporation, and the PharmaEssentia logo is a trademark of PharmaEssentia Corporation.

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New Data on Ropeginterferon Alfa-2b to Be Featured at EHA2022 - Business Wire

From cities in the sky to robot butlers, futuristic visions fill the history ofPopSci. In theAre we there yet?column we check in on progress towards our most ambitious promises. Read the series and explore all our 150th anniversary coveragehere.

In 1923, Popular Science reported that people were drinking radium-infused water in an attempt to stay young. How far have we come to a real (and non-radioactive) cure for aging?

From the time Marie Curie and her husband Pierre discovered radium in 1898, it was quickly understood that the new element was no ordinary metal. When the Curies finally isolated pure radium from pitchblende (a mineral ore) in 1902, they determined that the substance was a million times more radioactive than uranium. At the time, uranium was already being used in medicine to X-ray bones and even treat cancer tumors, a procedure first attempted in 1899 by Tage Sjogren, a Swedish doctor. Coupled with radiums extraordinary radioactivity and unnatural blue glow, the mineral was soon touted as a cure for everything including cancer, blindness, and baldness, even though radioactivity had only been used to treat malignant tumors. As Popular Science reported in June 1923, it was even believed that a daily glassful of radium-infused water would restore youth and extend life, making it the latest in a long line of miraculous elixirs.

By May 1925 The New York Times was among the first to report cancer cases linked to radium. Two years later, five terminally ill women, who became known as the Radium Girls, sued the United States Radium Corporation where they had worked, hand-painting various objects with the companys poisonous pigment. As more evidence emerged of radiums carcinogenic effects, its cure-all reputation quickly faded, although it would take another half-century before the last of the luminous-paint processing plants was shut down. Radium is still used today in nuclear medicine to treat cancer patients, and in industrial radiography to X-ray building materials for structural defectsbut its baseless status as a life-extending elixir was short-lived.

And yet, radiums downfall did not end the true quest for immortality: Our yearning for eternal youth continues to inspire a staggering range of scientifically dubious products and services.

Since the early days of civilization, when Sumerians etched one of the first accounts of a mortal longing for eternal life in the Epic of Gilgamesh on cuneiform tablets, humans have sought a miracle cure to defy aging and defer death. Five thousand years ago in ancient Egypt, priests practiced corpse preservation so a persons spirit could live on in its mummified host. Fortunately, anti-aging biotech has advanced from mummification and medieval quests for the fountain of youth, philosophers stone, and holy grail, as well as the perverse practices of sipping metal-based elixirs, bathing in the blood of virgins, and even downing Radium-infused water in the early 20th century. But what hasnt changed is that the pursuit of eternal youth has largely been sponsored by humankinds wealthiest citizens, from Chinese emperors to Silicon Valley entrepreneurs.

Weve all long recognized that aging is the greatest risk factor for the overwhelming majority of chronic diseases, whether it be Alzheimers disease, cancer, osteoporosis, cardiovascular diseases, or diabetes, says Nathan LeBrasseur, co-director of The Paul F. Glenn Center for Biology of Aging Research at the Mayo Clinic in Minnesota. But weve really kind of said, well, theres nothing we can do about senescence [cellular aging], so lets move on to more prevalent risk factors that we think we can modify, like blood pressure or high lipids. In the last few decades, however, remarkable breakthroughs in aging research have kindled interest and opened the funding spigots. Fortunately, the latest efforts have been grounded in more established scienceand scientific methodsthan was available in radiums heyday.

In the late 19th century, just as scientists began zeroing in on germs with microscopes, evolutionary biologist August Weismann delivered a lecture on cellular aging, or senescence. The Duration of Life (1881) detailed his theory that cells had replication limits, which explained why the ability to heal diminished with age. It would take 80 years to confirm Weismanns theory. In 1961, biologists Leonard Hayflick and Paul Moorhead observed and documented the finite lifespan of human cells. Another three decades later, in 1993, Cynthia Kenyon, a geneticist and biochemistry professor at the University of California, San Francisco, discovered how a specific genetic mutation in worms could double their lifespans. Kenyons discovery gave new direction and hope to the search for eternal youth, and wealthy tech entrepreneurs were eager to fund the latest quest: figuring out how to halt aging at the cellular level. (Kenyon is now vice president of Calico Research Labs, an Alphabet subsidiary.)

Weve made such remarkable progress in understanding the fundamental biology of aging, says LeBrasseur. Were at a new era in science and medicine, of not just asking the question, what is it about aging that makes us at risk for all these conditions? But also is there something we can do about it? Can we intervene?

In modern aging research labs, like LeBrasseurs, the focus is to tease apart the molecular mechanisms of senescence and develop tools and techniques to identify and measure changes in cells. The ultimate goal is to discover how to halt or reverse the changes at a cellular level.

But the focus on the molecular mechanisms of aging is not new. In his 1940 book, Organisers and Genes, theoretical biologist Conrad Waddington offered a metaphor for a cells life cyclehow it grows from an embryonic state to something specific. In Waddingtons epigenetic landscape, a cell starts out in its unformed state at the top of a mountain with the potential to roll downhill in any direction. After encountering a series of forks, the cell lands in a valley, which represents the tissue it becomes, like a skin cell or a neuron. According to Waddington, epigenetics are the external mechanisms of inheritanceabove and beyond standard genetics, such as chemical or environmental factorsthat lead the cell to roll one way or another when it encounters a fork. Also according to Waddington, who first proposed the theory of epigenetics, once the cell lands in its valley, it will remain there until it diesso, once a skin cell, always a skin cell. Waddington viewed cellular aging as a one-way journey, which turns out to be not so accurate.

We know now that even cells of different types keep changing as they age, says Morgan Levine, who until recently led her own aging lab at the Yale School of Medicine, but is now a founding principal investigator at Altos Labs, a lavishly funded startup. The [Waddington] landscape keeps going. And the new exciting thing is reprogramming, which shows us that you can push the ball back the other way.

Researchers like Levine continue to discover new epigenetic mechanisms that can be used to not only determine a cells age (epigenetic or biological clock) but also challenge Waddingtons premise that a cells life is one way. Cellular reprogramming is an idea first attempted in the 1980s and later advanced by Nobel Prize recipient Shinya Yamanaka, who discovered how to revert mature, specialized cells back to their embryonic, or pluripotent, state, enabling them to start fresh and regrow, for instance, into new tissue like liver cells or teeth.

I like to think of the epigenome as the operating system of a cell, Levine explains. So more or less all the cells in your body have the same DNA or genome. But what makes the skin cell different from a brain cell is the epigenome. It tells a cell which part of the DNA it should use thats specific to it. In sum, all cells start out as embryonic or stem cells, but what determines a cells end state is the epigenome.

Theres been a ton of work done with cells in a dish, Levine adds, including taking skin cells from patients with Alzheimers disease, converting them back to stem cells, and then into neurons. For some cells, you dont always have to go back to the embryonic stem cell, you can just convert directly to a different cell type, Levine says. But she also notes that what works in a dish is vastly different from what works in living specimens. While scientists have experimented with reprogramming cells in vivo in lab animals with limited success, the ramifications are not well understood. The problem is when you push the cells back too far [in their life cycle], they dont know what theyre supposed to be, says Levine. And then they turn into all sorts of nasty things like teratoma tumors. Still, shes hopeful that many of the problems with reprogramming may be sorted out in the next decade. Levine doesnt envision people drinking cellular-reprogramming cocktails to stave off agingat least not in the foreseeable futurebut she does see early-adopter applications for high-risk patients who, lets say, can regrow their organs instead of requiring transplants.

While the quest for immortality is still funded largely by the richest of humans, it has morphed from the pursuit of mythical objects, miraculous elements, and mystical rituals to big business, raising billions to fund exploratory research. Besides Calico and Altos Labs (funded by Russian-born billionaire Yuri Milner and others), theres Life Biosciences, AgeX Therapeutics, Turn Biotechnologies, Unity Biotechnology, BioAge Labs, and many more, all founded in the last decade. While theres considerable hype for these experimental technologies, any actual products and services will have to be approved by regulatory agencies like the Food and Drug Administration, which did not exist when radium was being promoted as a cure-all in the US.

While were working on landing long-term moon shots like editing genomes with CRISPR and reprogramming epigenomes to halt or reverse aging, LeBrasseur sees near-term possibilities in repurposing existing drugs to prop up senescent cells. When a cell gets old and damaged, it has one of three choices: to succumb, in which case it gets flushed from the system; to repair itself because the damage is not so bad; or to stop replicating and hang around as a zombie cell. Not only do [zombie cells] not function properly, explains LeBrasseur, but they secrete a host of very toxic molecules known as senescence associated secretory phenotype, or SASP. Those toxic molecules trigger inflammation, the precursor to many diseases.

It turns out there are drugs, originally targeted at other diseases, that are already in anti-aging trials because theyve shown potential to impact cell biology at a fundamental level, effectively staving off senescence. Although rapamycin was originally designed to suppress the immune system in organ transplant patients, and metformin to assist diabetes patients, both have shown anti-aging promise. When you start looking at data from an epidemiological lens, you recognize that these individuals [like diabetes patients taking metformin] often have less cardiovascular disease, notes LeBrasseur. They also have lower incidence of cancer, and theres some evidence that they may even have lower incidence of Alzheimers disease. Even statins (for cardiovascular disease) and SGL2 inhibitors (another diabetes drug) are being explored for a possible role in anti-aging. Of course, senescence is not all bad. It plays an important role, for example, as a protective mechanism against the development of malignant tumorsso tampering with it could have its downsides. Biology is so smart that weve got to stay humble, right? says LeBrasseur.

Among other things, the Radium Girls taught us to avoid the hype and promise of new and unproven technologies before the pros and cons are well understood. Weve already waited millennia for a miracle elixir, making some horrific choices along the way, including drinking radioactive water as recently as a century ago. The 21st century offers its own share of anti-aging quackery, including unregulated cosmetics, questionable surgical procedures, and unproven dietary supplements. While we may be closer than weve ever been in human history to real solutions for the downsides of aging, there are still significant hurdles to overcome before we can reliably restore youth. It will take years or possibly decades of research, followed by extensive clinical trials, before todays anti-aging research pays dividendsand even then its not likely to come in the form of a cure-all cocktail capable of bestowing immortality. In the meantime, LeBrasseurs advice is simple for those who can afford it: You dont have to wait for a miracle cure. Lifestyle choices like physical activity, nutritional habits, and sleep play a powerful role on our trajectories of aging. You can be very proactive today about how well you age. Unfortunately, not everyone has the means to follow LeBrasseurs medical wisdom. But the wealthiest among usincluding those funding immortalitys questmost definitely do.

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Radium was once cast as an elixir of youth. Are todays ideas any better? - Popular Science

Owing to Rising Demand for Less Invasive Treatments Among Heart Patients, Fact.MR Study Opines the Global Bioabsorbable Stents Market Share is Estimated to Reach a Value of Nearly US$ 1 Billion by 2032 from US$ 372 Million in 2021

Growing incidences of physicians and healthcare professionals preferring bioabsorbable stents over conventional stents is believed to have rapidly surged the bioabsorbable stent market growth in the global market.

Fact.MR, a Market Research and Competitive Intelligence Provider - The global bioabsorbable stents market is predicted to witness a moderate growth rate of 9.6% during the forecast years 2022 to 2032. The net worth of the bioabsorbable stents market share is expected to be valued at around US$ 1 Billion by the year 2032, growing from a mere US$ 372 Million recorded in the year 2021.

The growing prevalence of cardiovascular disease is sighted to be the leading cause of heart-related mortality worldwide. Around 17.5 million people die each year as a result of cardiovascular disease as a consequence of changing lifestyles, dietary habits, and rising blood pressure difficulties. All these factors have boosted the demand for bioabsorbable stents in the global market.

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Cardiovascular illnesses were responsible for more than 32% of fatalities in 2015, and this number is anticipated to grow to 45 per cent by 2030. The number of people diagnosed with diabetes has increased. Obesity, which is the leading cause of type 2 diabetes in adults, has increased as a result of changes in trends, food patterns, and regular exercise. The proliferation of such correlated diseases is suggested to be the major driving factor for the sales of bioabsorbable stents across the globe.

However, due to an increase in the prevalence of coronary artery disease, increased knowledge of bioabsorbable stents, increased demand for minimally invasive surgery, and increased adoption of unhealthy lifestyles, Asia-Pacific is predicted to have the highest CAGR from 2021 to 2032.

What is the Bioabsorbabale Stents Market Outlook in Asia Pacific Region?

As per the global market study on bioabsorbable stents, Asia Pacific is predicted to develop at the quickest rate. The rising number of cardiac patients in the Asia Pacific countries with the highest population count is predicted to drive the demand for bioabsorbable stents in the regional market.

During the projected period, the China bioabsorbable stents market is predicted to lead at the fastest rate of 8.8% in this geographical region. The net worth of the market is estimated to be around US$ 28 Million in 2022 and is projected to reach a total valuation of US$ 71.6 Million in the year 2032.

Other than that, bioabsorbable stents market opportunities in Japan and South Korea are also quite promising for the forecasted years, with an estimated growth rate of 8.1% and 7.3%, respectively. This new market research report on bioabsorbable stents also sheds light on the growth prospects in Indian Market as well.

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Competitive Landscape

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Recent Developments in the Market

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Our healthcare consulting team guides organizations at each step of their business strategy by helping you understand how the latest influencers account for operational and strategic transformation in the healthcare sector. Our expertise in recognizing the challenges and trends impacting the global healthcare industry provides indispensable insights and support - encasing a strategic perspective that helps you identify critical issues and devise appropriate solutions.

Point of Care Diagnostics Market - Shipments of point of care test (POCT) kits are projected to surge at a CAGR of around 7% from 2021 to 2028, as per this new analysis. In 2020, the global point of care diagnostics market stood at US$ 34.1 Bn, and is anticipated to surge to a valuation of US$ 66 Bn by the end of 2028.

Spectrometry Market - The global spectrometry market is projected to increase from a valuation of US$ 7.1 Bn in 2020 to US$ 13.8 Bn by 2028, expanding at a CAGR of 6.4% during the forecast period, Demand for mass spectrometry is set to increase faster at a CAGR of 7.4% over the forecast period 2021-2028.

Coronary Stents Market- Worldwide sales of coronary stents were valued at around US$ 10.1 Bn in 2020. The global coronary stents market is projected to register 12.9% CAGR and reach a valuation of US$ 25.7 Bn by the end of 2028.

Osteoporosis Therapeutics Market- The global osteoporosis therapeutics market stands at a valuation of US$ 12.7 Bn currently, and is predicted to reach US$ 14.2 Bn by the end of 2026. Consumption of osteoporosis therapeutic drugs is anticipated to increase at a CAGR of 2.9% from 2022 to 2026.

CNS Therapeutics Market- The CNS therapeutics market stands at a valuation of US$ 116.7 Bn in 2022, and is expected to reach US$ 142.1 Bn by the end of 2026. CNS drug sales are projected to rise at a steady CAGR of 4.9% from 2022 to 2026.

Induced Pluripotent Stem Cell (iPSC) Market- The global induced pluripotent stem cell (iPSC) market stands at a valuation of US$ 1.8 Bn in 2022, and is projected to climb to US$ 2.3 Bn by the end of 2026. Over the 2022 to 2026 period, worldwide demand for induced pluripotent stem cells is anticipated to rise rapidly at a CAGR of 6.6%.

Doxorubicin Market- Demand for doxorubicin is anticipated to increase steadily at a CAGR of 5.3% from 2022 to 2026. At present, the global doxorubicin market stands at US$ 1.1 Billion, and are projected to reach a valuation of US$ 1.3 Billion by the end of 2026.

Heart Attack Diagnostics Market- The heart attack diagnostics market is predicted to grow at a moderate CAGR of 7.1% during the forecast period of 2022 to 2032. The global heart attack diagnostics market is estimated to reach a value of nearly US$ 22.2 Billion by 2032 by growing from US$ 10.4 Billion in 2021.

Smart Implants Market- The global smart implants market is estimated at US$ 3.9 billion in 2022, and is forecast to surpass a market value of US$ 22.2 billion by 2032. Smart implants are expected to contribute significantly to the global implants market, with demand surging at a CAGR of 19% from 2022 to 2032.

Facial Implants Market- The global facial implant market was valued at US$ 2.7 Billion in 2022, and is expected to rise at a 7.7% value CAGR, likely to reach US$ 5.6 Billion by the end of the 2022-2032 forecast period.

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Bioabsorbable Stents Market to Grow at a Fine CAGR of 9.6% through 2032: Improvements in Healthcare Infrastructure and Growing Geriatric Population to...

LONDON, May 26, 2022 (GLOBE NEWSWIRE) -- According to The Business Research Companys research report on the stem cell therapy market, North America was the largest region in the stem cell therapy market and was worth $2.16 billion in 2021. The market accounted for 0.009% of the region's GDP. In terms of per capita consumption, the market accounted for $4.3, $3.8 higher than the global average. The stem cell therapy market in North America is supported by factors including the presence of key players engaged in developing stem cell therapies; advanced healthcare infrastructure; extensive research and development; supportive reforms from healthcare organizations; and strong reimbursement policies. For instance, companies are collaborating from different parts of the world to fund and develop new methods for stem cell therapy. In 2021, RxCell, a USA-based biotechnology company specializing in stem cell therapy, will collaborate with the Agency for Science, Technology, and Research (A*STAR)s Institute of Molecular and Cell Biology (IMCB) to co-fund and develop cellular therapeutics for age-related diseases.The Agency for Science, Technology, and Research (A*STAR)s Institute of Molecular and Cell Biology (IMCB) is a Singaporean biotechnology institute.

Request for a sample of the global stem cell therapy market report

The global stem cell therapy market size is expected to grow from $10.67 billion in 2021 to $11.99 billion in 2022 at a compound annual growth rate (CAGR) of 12.4%. The growth in the market is mainly due to the companies resuming their operations and adapting to the new normal while recovering from the COVID-19 impact, which had earlier led to restrictive containment measures involving social distancing, remote working, and the closure of commercial activities that resulted in operational challenges. The stem cell therapy market is expected to reach $21.17 billion in 2026 at a CAGR of 15.3%.

To sustain product innovation in an increasingly competitive market, major companies in the animal stem cell therapy market as well as the placental stem cell therapy market are undertaking strategic initiatives such as collaborations, partnerships, and acquisitions. The advantages of strategic partnerships include sharing of resources, expansion of distribution, and promotion of products. For instance, in June 2021, Catalent, a New Jersey-based pharmaceutical company involved with gene therapies, announced the acquisition of RheinCell Therapeutics, a company specializing in the GMP-compliant generation of human-induced pluripotent stem cells (iPS cells) and therapies, for an undisclosed amount. Through this acquisition, Catalent further strengthens its cell therapy portfolio and offers enhanced iPSC-based cell therapy capabilities. RheinCell Therapeutics is headquartered in Langenfeld, Germany, and was founded in 2017. In June 2020, Century Therapeutics, a US based developer of induced pluripotent stem cell-derived allogeneic cell therapies, announced the acquisition of Empirica Therapeutics for an undisclosed amount. This acquisition will leverage Century Therapeutics' iPSC-derived allogeneic cell therapies against glioblastoma (GBM). Empirica Therapeutics is a Canada-based developer of therapeutic drugs designed to treat aggressive forms of cancer.

Major players in the stem cell therapy market are Anterogen, JCR Pharmaceuticals, Medipost, Osiris Therapeutics, Pharmicell, Astellas Pharma, Cellectis, Celyad, Novadip Biosciences, Gamida Cell, Capricor Therapeutics, Cellular Dynamics, CESCA Therapeutics, DiscGenics, OxStem, Mesoblast, ReNeuron Group, Takeda Pharmaceuticals, Magellan, Kolon TissueGene, Stemedica Cell Technologies, Holostem Terapie Avanzate S.r.l., NuVasive, RTI Surgical, and AlloSource.

The global stem cell therapy market is segmented by type into allogeneic stem cell therapy, autologous stem cell therapy; by cell source into adult stem cells, induced pluripotent stem cells, embryonic stem cells; by application into musculoskeletal disorders, wounds and injuries, cancer, autoimmune disorders, others; by end-user into hospitals, clinics.

The Middle East is expected to be the fastest growing region in the forecast period. The regions covered in the stem cell market analysis report are Asia-Pacific, Western Europe, Eastern Europe, North America, South America, the Middle East, and Africa.

Stem Cell Therapy Global Market Report 2022 Market Size, Trends, And Global Forecast 2022-2026 is one of a series of new reports from The Business Research Company that provide stem cell therapy market overviews, stem cell therapy market analyze and forecast market size and growth for the whole market, stem cell therapy market segments and geographies, stem cell therapy market trends, stem cell therapy market drivers, stem cell therapy market restraints, stem cell therapy market leading competitors revenues, profiles and market shares in over 1,000 industry reports, covering over 2,500 market segments and 60 geographies.

The report also gives in-depth analysis of the impact of COVID-19 on the market. The reports draw on 150,000 datasets, extensive secondary research, and exclusive insights from interviews with industry leaders. A highly experienced and expert team of analysts and modelers provides market analysis and forecasts. The reports identify top countries and segments for opportunities and strategies based on market trends and leading competitors approaches.

Not the market you are looking for? Check out some similar market intelligence reports:

Cellular Immunotherapy Global Market Report 2022 By Therapy (Tumour-Infiltrating Lymphocyte (TIL) Therapy, Engineered T Cell Receptor (TCR) Therapy, Chimeric Antigen Receptor (CAR) T Cell Therapy, Natural Killer (NK) Cell Therapy), By Primary Indication (B-Cell Malignancies, Prostate Cancer, Renal Cell Carcinoma, Liver Cancer, Non-Hodgkin Lymphoma), By Application (Prostate Cancer, Breast Cancer, Skin Cancer, Ovarian Cancer, Brain Tumour, Lung Cancer) Market Size, Trends, And Global Forecast 2022-2026

Cell Therapy Technologies Global Market Report 2022 By Product (Consumables, Equipment, Systems & Software), By Cell Type (T-Cells, Stem Cells, Other Cells), By Process (Cell Processing, Cell Preservation, Distribution, And Handling, Process Monitoring And Quality Control) Market Size, Trends, And Global Forecast 2022-2026

Cell Therapy Global Market Report 2022 By Technique (Stem Cell Therapy, Cell Vaccine, Adoptive Cell Transfer (ACT), Fibroblast Cell Therapy, Chondrocyte Cell Therapy), By Therapy Type (Allogeneic Therapies, Autologous Therapies), By Application (Oncology, Cardiovascular Disease (CVD), Orthopedic, Wound Healing) Market Size, Trends, And Global Forecast 2022-2026

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North America is the largest region in the Stem Cell Therapy Market, worth $2 Billion in 2021. What does the future hold? As Per The Business Research...

According to reports, currently, 64.34 million people suffer from heart failure worldwide[1]. Furthermore, the number of patients with end-organ heart failure is rising, leading to an all-time high in the number of people waiting for an organ transplant[2]. Several strategies have been devised to increase this strained supply of heart for transplantation, including expanding donor criteria[3], use of advanced perfusion machines such as organ care systems (OCS) to improve viability[4], use of normothermic regional perfusion (NRP) in donor from cardiac death (DCD) hearts, and xenotransplantation. Recently, the focus has shifted to new procedures using regenerative cells, angiogenesis factors, biological matrices, biocompatible synthetic polymers, and online registry systems that utilize bioimplants. These advanced technologies are collectively referred to as tissue engineering[5-8]. Ultimately, the goal is to grow a heart de novo. In addition to the unlimited organ supply, the new organ would be antigenically identical to the recipient as the recipients cells would be used, eliminating the need for immunosuppressive agents.

Even though bioengineering a fully functioning heart is in its infancy, huge strides have been made in achieving this goal. Scientists have been able to bioengineer models of the heart, lungs, pancreas, liver, and kidney. An important strategy for supporting the recipients cells and creating an autologous tissue/organ is to create a mechanical, geometrical, and biological environment that closely mimics the native organs properties. The breakthrough in growing an artificial heart was the invention of the decellularization of extracellular matrix (ECM), which maintains the native vascular network[9]. Numerous tissues and organs have been engineered using decellularization, including livers [10], lungs[11], kidneys[12], corneas[13], bladders[14], vasculature[15], articular cartilage[16], intestines[17], and hearts[18]. There has been some success in engineering a heart in the lab. Although technological innovations and biological model systems have resulted in great progress, constructing such complicated tissue structures effortlessly remains a challenge. This review aims to outline the techniques involved in bioengineering a heart in the lab and the challenges involved in developing it into a viable organ for transplantation (Figure 1).

The human heart comprises various cells, each specialized to perform a specific task. A human heart contains roughly 2-3 billion cardiomyocytes, making up only about one-third of its total cells [19]. Additionally, other cells include endothelial cells, fibroblasts, and specialized conducting cells like Purkinje fibers. On top of that, structural scaffolds support the functions of cells arranged into structures, such as vessels, muscles, and nerves. These scaffolds mainly consist of polysaccharides and proteoglycans embedded in complex sugars and chemokines matrix, allowing the heart to coordinate its mechanical and electrical functions [20,21]. Sprawled around this is a collection of protein fibers such as collagen and elastin, which confers mechanical strength to the heart and allow for the constant loading and unloading forces[22,23]. Thus, it is necessary to construct a scaffold around which the specialized cells can grow and maintain vitality through blood perfusion to recreate a functioning heart in a laboratory [24] (Figure 2).

Extracellular matrix (ECM) and cells in an organ display a dynamic reciprocity, whereby the ECM constantly adapts to the demands of the cells[25], and selecting the appropriate scaffold is the key component for growing a viable organ in the lab. Researchers have also studied various synthetic scaffolds as potential surrogates for the ECM, but none can replicate its intricacy or structure compared to native ECM. It is possible to vascularize synthetic materials such as polylactic acid (PLLA) and polylactic glycolic acid (PLGA) and to produce them consistently[26,27]. The significant advantage of synthetic ECM is its production scalability as it does not require to be harvested from living tissue, but these do not match the native myocardiums tensile strength. Hydrogels have also been studied extensively and even accepted by the Food and Drug Administration for drug delivery and adjunct for cell therapy. Hydrogels consist of a cross-linked hydrophilic polymer matrix with over 30% water content [28]. However, they have poor cell retention [29] or poor tensile strength [30]; hence, they are not feasible as a primary scaffold for constructing an organ. Decellularizing the whole heart and leaving the ECM serves as a potential solution to this problem with the particular advantage of having a balanced composition of all the proteins present physiologically [31].

The Badylak laboratory developed the first technique for decellularizing tissue[32]. This process involved the removal of the cell, leaving only the ECM, which retained its composition, architecture, and mechanical properties. There are several methods for removing cells from the ECM. These methods include physical methods (e.g., freeze/thaw cycles), enzymatic degradation (e.g., trypsin), and removal by using chemicals (e.g., sodium dodecyl sulfate)[33]. Ott et al. noted that decellularization could be achieved with different detergent solutions. Comparative studies on decellularization methods have mixed results regarding the superiority of different techniques [34-37]. Based on the results, the sodium dodecyl sulfate (SDS) solution was found to be the best [18]. However, a few studies have suggested that SDS treatment causes degradation of the ECM with a reduction in elastin, collagen, and glycosaminoglycans (GAG) content [34]. The decellularization process utilizes 1% SDS perfused through the coronary circulation, followed by washing it with de-ionized water and subsequently 1% Triton-X-100 (Sigma). Finally, the organ remnant is washed with phosphate-buffered saline (PBS) wash buffer, antibiotic, and protease, leaving a decellularized ECM[38,39]. Using this technique, they decellularized the heart, reseeded it with neonatal cardiac cells, and grew the first beating rodent heart in the lab [18]. Decellularized tissue provides a dynamic environment for the orientation and coupling of cells and facilitates the exchange of nutrients and oxygen throughout the depth of the tissue. Moreover, this process efficiently removes both allogeneic and xenogeneic antigens, possibly preventing the need for immunosuppressants [33], which is especially important as one of the causes of heart failure in transplanted hearts is myocardial fibrosis from chronic rejection [40]. This process can be potentially avoided by using a decellularized heart to generate an ECM scaffold which can then be repopulated using the recipients cells.

Researchers have used animal heart ECM and human heart ECM scaffolds to provide this decellularized ECM scaffold. The porcine heart has often been deemed suitable for its similarity with the human heart [41]. As decellularization removes most of the cells, much of the antigen load is removed. However, the porcine heart ECM contains -1,3-galactose epitope (-gal), which can stimulate an immune response [42,43]. One way to circumvent this is to use pigs lacking -gal epitope, but this technique needs further research. Another possible problem with using a porcine heart is the possible risk of horizontal transmission of porcine viruses like the porcine endogenous retrovirus, cytomegalovirus, HSB, circovirus, etc. [44,45]. Although a few tests can detect the presence of these viruses, they have poor sensitivity, and hence further work has to be done [46].

A cadaveric heart that is unfit for transplant can also be used to harvest an ECM scaffold [47]. The only drawback to this is that it may not always be possible to achieve the desired level of tissue engineering fidelity with these matrices because they may be damaged or diseased. Moreover, there is an assumption that they are superior for the growth and differentiation of human cells, but there is no robust evaluation to support this assumption. The method for decellularization of the cadaveric human heart is similar to that of other animals, utilizing 1% SDS and 1% Triton X-100, with the only difference being a longer perfusion time for these chemicals [48,49].

These cells are highly specialized and terminally differentiated, and hence, they do not proliferate normally. Therefore, to repopulate a human-sized scaffold, autologous human cardioblasts must be isolated or expanded in large quantities. Hence, for the recellularization of ECM, a method of inducing progenitor cells had to be devised. Thus, the discovery of methods to reprogram or induce adult cells into pluripotent stem cells was a significant milestone in stem cell biology and tissue bioengineering[50-52].

Once we have the cells for repopulation of ECM, recellularization is required to achieve a functional organ product for implantation. For recellularization to be achieved, choosing appropriate cell sources, seeding cells optimally, and cultivating them using organ-specific cultures are needed [24]. Cells from fetuses and adults, embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs) have all been used[24]. Obtained with ease and ethically, stem cells from bone marrow stroma or adipose tissue (MSC) have shown promise as the ideal cells for recellularization [53]. In addition, human somatic cells can be reprogrammed to produce iPSCs, and they exhibit properties similar to ESCs [54].

A potential solution to the problem of getting a large number of human cells for tissue engineering or other regenerative medicine approaches is the ability to produce iPSCs from readily available autologous cells such as fibroblasts or blood cells[55,56]. The only drawback to using iPSCs is the possibility of teratoma formation due to its pluripotent nature [48,57]. However, the potential solution to this problem is to allow controlled differentiation toward a cardiac lineage before implantation into the ECM [58]. Although previously any attempts to produce iPSCs would result in karyotype instability [59], recent advances have been made with iPSCs maintaining chromosomal integrity [60]. These advances have ushered astep forward in the pursuit of creating viable organs in the lab.

Cell seeding techniques depend on the type of organ being engineered, and, for the heart, it usually involves seeding by perfusion through the vascular tree [24]. This step is called re-endothelization and is usually the first step to recellularization. A dynamic communication between endothelial cells and cardiomyocyte populations occurs via direct cell interactions and the secretion of various factors[61,62]. It is evident from multiple reports that seeding endothelial cell populations and cardiomyocyte populations simultaneously provides functional benefits that aid in maintaining the recellularization process [63]. Interestingly, endothelial cells have also demonstrated the ability to differentiate into cardiomyocytes in other cardiomyocyte cells [64], which may aid in more efficient recellularization. Moreover, besides the advantage, the recellularization of both the vascular tree and the heart parenchyma must be uniform to prevent two key issues in the heart, namely, thrombogenesis[65] and arrhythmogenesis[66].

Improved cell concentration and diffusion over the scaffold can be achieved by optimizing the mechanical environment, scaffold coating, and cell perfusion systems by using multiple perfusion routes simultaneously, which for the heart involves both direct intramyocardial injections and perfusion of the vascular tree [67]. However, the potential problem with intramyocardial injections is that even though the injection site shows dense cellularity, the cells are generally poorly distributed throughout the scaffold [58]. Moreover, sequential injections of cardiac cells will likely be required to rebuild the chamber parenchyma, which may compromise matrix integrity [48]. Nevertheless, given that cardiac cells include fibroblasts, in which ECM is produced and secreted, there is a possibility that endogenous matrix repair may occur after cell seeding to help resolve this issue [62].

While sourcing cells for recellularization using stem cells is a work in progress, multiple studies have explored ways to develop mature cardiomyocytes derived from iPSCs that are more physiologically similar to native cardiomyocytes [68,69]. One of the most recent cardiac constructs was engineered using PSC-derived cardiac cells in a ratio of equal cardiomyocyte and noncardiomyocyte cells, cultured in serum-free media [70]. Cardiomyocytes cultivated in this method were elongated, had organized sarcomeres and distinguished bands, and exhibited increased contractility [70]. It is encouraging to see these results that stem cells can be used to produce cardiomyocytes similar to native mature cells, reinforcing the notion that stem cells can be a cardiac cell source.

After enough cells have been seeded onto an organ scaffold, cell culture is required. A bioreactor is required for perfusion and provides a nutrient-rich environment that encourages organ-specific cell growth [24]. Bioreactors should allow nutrient-rich oxygen to be pumped with adjustable rates of flow and pressure and monitor and control the pH and temperature of the media. Moreover, mechanical stimulation is also an essential component for engineering organs of the musculoskeletal and cardiovascular systems [71]. A wide range of mechanical properties is employed in the design of bioreactors, including substrate stiffness and dynamic changes in stiffness throughout culture, pulsatile flow, and providing stretch to enhance cell maturation, alignment, and generation of force in engineered constructs [72]. Presently, there are several types of bioreactors available, with Radnoti [73] and BIOSTAT B-DCU II [74], to name a few. In addition, there has been an increase in bioreactor designs incorporating real-time monitoring to assess the status of engineered tissues. These designs may incorporate biochemical probes to assess transmural pressure changes or sampling ports to test cells viability and biochemical composition after recellularization [75,76]. The incorporation of sampling methods within bioreactor designs will keep constructs sterile, allowing for modifications in stimuli to be made while maintaining a closed system, and providing researchers with valuable feedback on cell responses throughout bioengineering. Further research is being conducted to make bioreactors that can be used to maintain the perfect milieu for growing these bioengineered tissues and organs.

For an organ to be viable for transplant, three things must be ensured: sterility of the process, structural integrity, and, lastly, patency for surgical anastomosis. Biological tissues are sterilized by gamma radiations or peracetic acid at low concentrations before the ECM is repopulated with cells[77]. Once the cells are added, antibacterial, antifungals, and other antibiotic drugs can be utilized. It is re-evaluated for integrity before the ECM is recellularized and only gets the green light for cell seeding if structural integrity is maintained. Interestingly, with the aid of endoscopy, decellularized constructs can be easily manipulated and visualized for macro and microstructure defects at the level of chambers, papillary muscle, and valves[47]. One of the most important aspects of evaluating the integrity of ECM is to check for intact coronary vasculature, which can be done by micro-optical coherence tomography [48].

Heart constructs engineered in the lab have been demonstrated to undergo cyclical muscular contraction but also have been shown to respond to drugs and exhibit electrical activity. However, electrocardiography analysis of the bioengineered hearts has shown irregular wave morphology due to loss of coupling between cardiomyocytes [78]. Therefore, it will be crucial to develop continuous monitoring of cardiac electrophysiology, function, and even vascular patency if these artificial constructs can be transplanted into patients.

Over the past decade, research in regenerative medicine has enabled us to understand better the challenges associated with developing a bioartificial heart. The first challenge was creating a biocompatible scaffold which has already been resolved with the development of various decellularization techniques, making it possible to generate an anatomically accurate and vascularized heart scaffold. With the advent of newer techniques for iPSC generation of stable karyotype, cell generation is also potentially resolved. Presently, research has to be aimed to address the challenges in reseeding the ECM scaffold. A potential solution might be the advancement in 3D-printed matrixes with embedded cells. However, decellularized ECM remains the gold standard for now as 3D-printed matrixes cannot replicate the complexity and structural integrity of the natural component of ECM.

Another potential problem is the creation of a bioreactor that can efficiently maintain the environment required for the growth of cardiac and other differentiated cells around the decellularized ECM scaffold. Constructing organs is no easy feat and involves much technical expertise. Hence, many resources are required in every step of artificially reproducing tissues and organs. Thus, even if bioengineering a heart is a possibility in the near future, it may not be financially feasible to use them for transplantation until the cost of making such constructs is lowered. Additionally, we do not know the long-term viability of such constructs. These constructs use chemicals to decellularize ECM as well as induce the conversion of adult cells into pluripotent cells. Some questions arise on how the complex network of cells and ECM would interact over the long run. The heart is a complex organ that requires a highly specialized conduction system to ensure efficient, coordinated, and purposeful contraction of the heart chambers. Any deviance may lead to fatal arrhythmia or thrombus formation. We are yet to reproduce a perfect conduction system in the lab, let alone test its long-term functionality. Furthermore, the use of induced pluripotent cells also raises the prospect of long-term tumorigenesis and malignancy. Despite rapid advances in bioengineering and artificial hearts, research and clinical trials must be conducted to determine the long-term feasibility of using these organs.

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Is a Bioengineered Heart From Recipient Tissues the Answer to the Shortage of Donors in Heart Transplantation? - Cureus

DUBLIN--(BUSINESS WIRE)--The "Heart Failure - Pipeline Insight" clinical trials has been added to ResearchAndMarkets.com's offering.

This "Heart Failure - Pipeline Insight, 2022" report provides comprehensive insights about 90+ companies and 90+ pipeline drugs in Heart Failure pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space.

"Heart Failure - Pipeline Insight, 2022" report outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Heart Failure pipeline landscape is provided which includes the disease overview and Heart Failure treatment guidelines.

The assessment part of the report embraces, in depth Heart Failure commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, collaborations, licensing, mergers and acquisition, funding, designations and other product related details.

Report Highlights

Heart Failure Emerging Drugs

Tirzepatide: Eli Lilly and Company

Tirzepatide is a once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that integrates the actions of both incretins into a single novel molecule. GIP is a hormone that may complement the effects of GLP-1. In preclinical models, GIP has been shown to decrease food intake and increase energy expenditure therefore resulting in weight reductions, and when combined with a GLP-1 receptor agonist, may result in greater effects on glucose and body weight. Tirzepatide is in phase 3 development for chronic weight management and heart failure with preserved ejection fraction (HFpEF). It is also being studied as a potential treatment for non-alcoholic steatohepatitis (NASH). Both the FDA and EMA have accepted Eli Lilly's marketing approval applications for its type 2 diabetes treatment, tirzepatide.

Finerenone (BAY94-8862): Bayer

Finerenone (BAY 94-8862) is an investigational novel, non-steroidal, selective mineralocorticoid receptor antagonist (MRA) that has been shown to block the harmful effects of the overactivated mineralocorticoid receptor (MR) system. MR overactivation is a major driver of heart and kidney damage. Current steroidal MRAs on the market have proven to be effective in reducing cardiovascular mortality in patients suffering from heart failure with reduced ejection fraction (HFrEF). However, they are often underutilized due to the incidence of hyperkalemia, renal dysfunction, and anti-androgenic/ progestogenic side effects.

CardiAMP Cell Therapy: BioCardia

CardiAMP Cell Therapy uses a patient's own (autologous) bone marrow cells delivered to the heart in a minimally invasive, catheter-based procedure to potentially stimulate the body's natural healing response. The CardiAMP Cell Therapy Heart Failure Trial is the first multicenter clinical trial of an autologous cell therapy to prospectively screen for cell therapeutic potency in order to improve patient outcomes. CardiAMP Cell Therapy incorporates three proprietary elements not previously utilized in investigational cardiac cell therapy, which the company believes improves the probability of success of the treatment: a pre-procedural diagnostic for patient selection, a high target dosage of cells, and a proprietary delivery system that has been shown to be safer than other intramyocardial delivery systems and more successful for enhancing cell retention.

Rexlemestrocel-L (Revascor): Mesoblast

Revascor consists of 150 million mesenchymal precursor cells (MPCs) administered by direct injection into the heart muscle in patients suffering from CHF and progressive loss of heart function. MPCs release a range of factors when triggered by specific receptor-ligand interactions within damaged tissue. Based on preclinical data, it is believed that these factors induce functional cardiac recovery by simultaneous activation of multiple pathways, including induction of endogenous vascular network formation, reduction in harmful inflammation, reduction in cardiac scarring and fibrosis, and regeneration of heart muscle through activation of tissue precursors.

BMS-986231: Bristol-Myers Squibb

Cimlanod (development codes CXL-1427 and BMS-986231) is an experimental drug for the treatment of acute decompensated heart failure. HNO gas (nitroxyl) is a chemical sibling of nitric oxide. Although nitric oxide and HNO appear to be closely related chemically, the physiological effects and biologic mechanisms of HNO and nitric oxide action are distinct. The biologic effects of HNO are mediated by direct post-translational modification of thiol residues in target proteins, including SERCA2a, phospholamban, the ryanodine receptor, and myofilament proteins in cardiomyocytes. In vitro, HNO increases the efficiency of calcium cycling and improves myofilament calcium sensitivity, which enhances myocardial contraction and relaxation. HNO also mediates peripheral vasodilation through endothelial soluble guanylate cyclase. HNO does not induce tachyphylaxis in peripheral vessels, unlike nitric oxide.

Elamipretide: Stealth BioTherapeutics

Elamipretide (MTP-131, Bendavia) is a novel tetra-peptide that targets mitochondrial dysfunction in energydepleted myocytes. Elamipretide crosses the outer membrane of the mitochondria and associates itself with cardiolipin, which is a phospholipid expressed only in the inner membrane of mitochondria. Cardiolipin has an integral role in mitochondrial stability and organization of respiratory complexes into super complexes for oxidative phosphorylation.Thus, elamipretide helps to enhance ATP synthesis in multiple organs of the body. Elamipretide has been shown to improve left ventricular ejection fraction (LVEF), LV end diastolic pressure, cardiac hypertrophy, myocardial fibrosis, and myocardial ATP synthesis in both animal models and humans.

FA relaxin: Bristol Myers Squibb

BMS-986259 is a next-generation version of Relaxin that is enabled with our technology and currently in Phase 1 clinical trials for ADHF. Relaxin, a peptide hormone, has been reported to reduce fibrosis in the multiple organs and to exert cardioprotective effects in preclinical studies. However, the therapeutic potential of Relaxin has been partially limited by its short half-life in humans. BMS-986259 has exhibited a prolonged half-life and therefore has the potential to enhance clinical benefit as a novel therapeutic for ADHF.

Key Players

Key Products

For more information about this clinical trials report visit https://www.researchandmarkets.com/r/soc45u

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Global Heart Failure Pipeline Market Research Report 2022: Comprehensive Insights About 90+ Companies and 90+ Pipeline Drugs - ResearchAndMarkets.com...

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Its a symbol of love and courage. It flutters with excitement and panic. It knows when to rest and when to quicken. But, most importantly, the heart is an extraordinary machine. These doors inside your heart [the valves] have to flap open and closed 100,000 times a day, says cardiologist James Wong. If you did that to your front door it would be gone in the afternoon.

Yet, as with all complex machinery, over time the heart can develop issues. One of the more insidious problems lies in its plumbing the coronary arteries which, when blocked, cause a heart attack.

One in every 25 deaths in Australia in 2020 was due to a heart attack. Thats the equivalent of 18 deaths a day, or one every 80 minutes. Sometimes, heart attacks are sudden and brutal. Other times, people dont realise they are having one. And they are often different for women and men.

So, how do you know if you are having a heart attack? What does a massive heart attack mean? Can you test for signs? And to what extent can you prevent them?

Credit:Artwork Matt Davidson

The heart is a pump made of muscle with its own electrical circuits and plumbing. Its job is to bring oxygen and nutrients to all our organs in just the right amount. It normally beats up to 100 times a minute more when you exercise. With each beat, it squeezes to circulate blood from the lungs to the rest of body then back again. Valves keep blood flowing in the right direction, pieces of thin, strong tissue like parachute material. Its amazing how resilient they are to withstand pressure without tearing, says Wong, an associate professor of medicine, who is director of the Royal Melbourne Hospitals echocardiography laboratory.

Its the best pump that Professor Garry Jennings knows of and the most hardy. Not many pumps work for 90 years, 100,000 times a day, says Jennings, the Heart Foundations chief medical adviser.

Its a lot of responsibility for an organ the size of a fist, but it has its own electrical system to help.

Tiny electrical impulses trigger each heartbeat, beginning in the sinus node at the top of the heart before travelling, like a Mexican wave, through the hearts four chambers two atria and two ventricles with the atria contracting a fraction of a second before the ventricles to push the blood. Wong likens the sinus node to the guy that beats the drum, which the rest of the heart follows, thereby controlling the heart rate.

Researchers have found that every time the heart beats, the brain pulses in sync ever so slightly.

An electrocardiogram, or ECG, produces the pulsing graph you see on screens at hospitals (and much beloved by makers of TV dramas). It detects the hearts contractions by reading its electrical activity via electrodes on the skin.

The heart contracts automatically, but the brains autonomic nervous system regulates the strength and pace of the contractions. The brain and heart depend on each other: the brain supports the hearts pumping, and the heart keeps the brain oxygenated. In fact, researchers have found that every time the heart beats, the brain pulses in sync ever so slightly.

But to do its job, the heart relies on having a rich blood supply, which is where its plumbing comes in: the coronary arteries are the blood vessels that wrap around the heart to nourish it with oxygenated blood. A heart attack occurs when that supply is impeded, cutting off nourishment and preventing the heart from keeping up with the demands of the body. The heart has to work pretty hard, and if you cut off the blood supply to a part of the muscle then it runs into trouble, says Jennings.

A heart attack is a medical event where blood flow in the coronary arteries becomes restricted, resulting in irreversible damage to the heart muscle. Because theres no blood flow being delivered to that part of the heart muscle, that part dies, Wong says.

The extent of the damage will vary but the consequences can be devastating, leading to a life sentence of chronic heart failure, or death.

What tends to determine a heart attacks severity is the location of the artery blockage and the time taken to clear it, as these two factors will dictate how much irreversible scarring is left behind.

You might hear that someone died of a massive heart attack. Picture the coronary arteries as being made up of three major freeways then side streets, avenues and laneways. Wong explains: If the blockage happened very much downstream and one of the side streets is blocked off, were not talking about a big volume of heart [thats low on supply]. Compare that to the start of the freeway being blocked then everything downstream is going to get wiped out because the narrowing happened to be at the wrong spot.

Blocked at the start of the freeway, the heart simply cant pump the blood out to the brain and other organs, and that can result in life-threatening cardiac shock. Wong says there is a particularly bad zone for a blockage, which is the left main stem where blood vessels lead into the heart. If it blocks off, probably two-thirds of the heart will go. That is not sustainable at all.

Its estimated that more than half of people killed by a heart attack die suddenly. In other cases, a blockage can harm the hearts electrical system causing cardiac arrhythmia, which can be fatal too: the hearts rhythm goes berserk and cant pump. The heart doesnt have time to fill then it cant empty properly. So its just fluttering instead of a regular beat in and out, Jennings says.

This can then lead to cardiac arrest, which is not the same as a heart attack, although heart attack is a common cause of cardiac arrest. You might think of a heart attack as more of a plumbing-related issue caused by a blockage while cardiac arrest is due to a malfunctioning of the hearts electrical system, prompting the heart to beat erratically thats where defibrillators come in, as an arrest is treated with electric shock.

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A heart attack is usually a result of coronary heart disease (also called ischaemic heart disease or coronary artery disease), an umbrella term for a range of conditions that can affect the heart when blood flow in the coronary arteries is compromised.

For some people, a heart attack is the first time a person realises they have the disease. Its Australias biggest killer overall; the leading cause of death in men, and, in women, it is the second-leading cause after dementia. Heart attacks are responsible for two-fifths of all coronary heart disease deaths.

Another important distinction: coronary heart disease is just one form of heart disease. Heart disease and cardiovascular disease are the same thing and are broad terms that include any disease of the heart or blood vessels, such as stroke and congenital heart conditions.

Angina, meanwhile, is a short-lived chest pain caused by blood flow issues its a sign of coronary heart disease but less intense than heart attack pain.

Most of us probably have an image in our heads of someone clutching their chest and collapsing. Wong says the textbooks dont always reflect real life but theyre the best place to start. People often get chest pains across the front of the chest, which radiate to their jaw or down their left arm. Its also associated with some breathlessness, sweatiness or nausea, he says.

Its not always like that, though. Women, for example, are less likely to have chest pains, more likely to have breathlessness, excessive sweating, dizziness or neck and back pain. One day in 2020, disability support worker Kath Moorby felt discomfort in her right shoulder and hand followed by tingling in her arms and fingers. Then she felt hot, clammy and sweaty. There was no chest pain, just a heaviness.

It was a surreal moment. Really? Im 44 and Im having a heart attack?

Paramedics eventually determined she was having a heart attack. It was a surreal moment, she recalls. Really? Im 44 and Im having a heart attack?

Moorby had two stents implanted. She says the effect was instant: the pressure in her upper-body reduced and her blood could flow freely again. They said I had a 20 per cent chance of surviving had I not made it to hospital when I did, she recalls.

Other people experience tightness rather than crushing pain.

People usually become cold, white and clammy, Jennings says. But symptoms can be variable.

Andrew van Vloten, a 53-year-old Victorian park ranger, had his first heart attack in 2014. With a family history of heart disease, he says, looking back, there had been signs for months that something was off: he felt occasional chest and jaw pain, especially when exercising, as well as shortness of breath. One day at work, the chest pains returned and wouldnt subside. It was getting quite intense, the pressure right on the centre of my chest I then started to get pins and needles in my fingers and toes. It was full-on, van Vloten says.

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He had a stent put in that day.

To avoid a repeat, he set about exercising more and ate less saturated fat, red meat and processed food. Six months down the track, I felt as fit as Id been in 10 years.

Its why he was so shocked when he had a second heart attack in 2020. This time he had no symptoms in the lead-up other than feeling a bit unwell. Then, as he was loading up timber into a ute, he was hit by nausea, breathlessness and chest pains. It just came on really quickly and intensely, he says. Everything started coming back to me.

It can be easy to mix up heart attack symptoms with heartburn, oesophageal spasms or angina. If the pain lasts more than 10 minutes, its worth seeking urgent medical attention. Its a heart attack when an artery blocks off and nothing a patient does makes it better, Jennings says.

Sometimes a heart attack can happen when the heart is under more pressure, such as during exercise or even following a big fright.Other times, theres no particular exertion. To complicate matters, one-sixth of people experience silent heart attacks no symptoms. This is more likely in people who have diabetes because their nerve endings can be blunted.

Sometimes we do ECGs on people for insurance purposes, and we find that theyve had an old heart attack somewhere along the way, Wong says. Its like if you damaged any part of you, you would scar, with scar tissue replacing the damaged tissue. The same thing happens in the heart.

Credit:Artwork Getty/Marija Ercegovac

They might seem to come out of the blue but a heart attack often reflects a process that has been going on throughout a persons life. Atherosclerosis is the narrowing and hardening of arteries. It starts in adolescence, if not before, brought on by a build-up of plaque (made of cholesterol and other substances) on the inner wall of the arteries. Once it gets underneath that inner lining of the vessel wall, its really hard to get out again, Wong says, so its almost like a one-way street.

By the time the guy whos been doing absolutely nothing, sitting all day, comes to you with chest pain, thats really late.

You wont be aware of much of the gradual narrowing because the body manages fine until it reaches a particular point. Its only once a coronary artery narrows by between 60 and 70 per cent that blood flow falls off noticeably and someone might begin to tire more easily or feel bursts of chest discomfort. That partly explains why some people feel great one week and dont feel good the next, Wong says.

This is also when coronary heart disease is in full swing. The artery wall becomes more unstable, so a blob of plaque can crack off and lead to clotting. This is the most common way a blockage happens before a heart attack but there are others. Sometimes, heart attacks occur in people without significantly clogged arteries, Wong says. There might be a spasm of the muscle lining in the artery that causes it to clamp down or, in rare cases (about 2 per cent of heart attacks) mainly in women, there can be a tear in the inner artery wall that peels off and blocks circulation (this is called spontaneous coronary artery dissection, or SCAD). Or plaque might simply be unstable, slough off and clog an artery more common in smokers.

Credit:Artwork Stephen Kiprillis

If someones exercise capacity is consistently worsening, it can be a sign their arteries are narrowing dangerously. It means when the heart is being asked to do more work, its not getting enough blood flow to it, Wong says. Maybe you used to be fine walking five kilometres, three the next month, then two; or walking room to room becomes too much. It will be unrelenting, its not something that would come and go away, Wong says. People need to be honest with themselves by the time the guy whos been doing absolutely nothing, sitting all day, comes to you with chest pain, thats really late. The artery is likely to be quite narrowed.

There are various tests you can do. As a first step, Wong advises his patients to try an online calculator such as cvdcalculator.com, where you punch in your data (for example, age, smoking status, cholesterol levels) to get an understanding of your risk and how making small lifestyle changes can make a big difference.

You dont have to have symptoms of heart disease to get a heart health check. Any patient over 30 is eligible.

A basic heart health check, usually done by a GP, can determine risk levels and help work out whether you are harbouring artery disease. You dont have to have symptoms of heart disease to get a heart health check. Any patient over 30 is eligible. Its covered by Medicare once in a 12-month period and is recommended for adults aged 45 and over, or Aboriginal and Torres Strait Islander people aged 30 and over.

A patient might have further tests if its appropriate, such as a calcium-score CT scan (more calcium deposits in the coronary arteries means theres a higher chance theyre narrowed) or an ECG or a cardiac stress test, which examines how the heart responds to exercise. These tests can cost a few hundred dollars, which Medicare generally covers only if someone has heart disease symptoms.

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To check to what extent someones arteries have narrowed, a coronary angiogram involves injecting dye into the hearts blood vessels, which is picked up using an X-ray machine.

Depending on the patient, they might be prescribed medication to treat cholesterol, blood pressure or clotting. Or a doctor might recommend inserting a stent or doing coronary artery bypass surgery to redirect blood flow by grafting a healthy blood vessel.

Its difficult not to be alarmed by the stories of fit, healthy people who collapse suddenly with a heart attack. Wong says these are rare events often caused by inherited, underlying heart disease. But anyone who has concerns can talk to their doctor about tests that will help them ascertain their hearts health, and what level of physical activity is safe for them.

Twice as many men are admitted to hospital with a heart attack compared to women, although the disparity in deaths is slimmer: in 2020, 2800 women and 3700 Australian men. This is, in large part, because of differences between how these events present in the two sexes studies having long shown that many women have their symptoms dismissed or misdiagnosed.

The average age of a first heart attack is 72 for women about 10 years older than men.

The average age of a first heart attack is 72 for women about 10 years older than men and theyre more likely to have a spontaneous artery tear, a blockage in a small coronary blood vessel or a mini heart attack where a smaller artery doesnt open up properly, despite no significant narrowing. The biology that causes heart attacks can be a bit more varied in women than men, Jennings says.

Women with a history of pre-eclampsia or gestational diabetes during pregnancy or endometriosis also have a higher risk of coronary heart disease.

There are some inequalities in who suffers most from heart attacks. The rate of hospitalisations and deaths is about 1.5 times higher for people in remote or lower socioeconomic areas, the Australian Institute of Health and Welfare reports. For Indigenous Australians, the rate is double that of non-Indigenous Australians.

People with diabetes are roughly four times more likely to have a heart attack. And mental health is important for the heart: depression can increase your risk of developing coronary heart disease just as much as smoking and high blood pressure.

Phone triple zero. While you wait for an ambulance, it helps to focus on breathing steadily to try to calm yourself. With any heart attack, Wong says the key is to have as short a door-to-needle time as possible. Normally, paramedics alert a hospital of a heart attack patient before arrival.

Sometimes theyll be given clot-dissolving medication, or a catheter tube is threaded up the arm or leg and a tiny balloon widens the narrowed coronary artery to leave behind a wire mesh, called a stent, to prop it open. Every minute counts in doing that, Jennings says, because the longer you wait, the more the heart muscle cells will be dying.

The part of the heart not affected by the blockage will keep working to contract, but it will be strained and the damage can spread. There is a risk of chronic heart failure, where the hearts pump mechanism is weakened long-term. They could be fine sitting or lying down but when they start walking up a hill, they cant do it. They have a limit and their lifestyle has to be adjusted to what the heart allows them to do, Wong explains. In severe heart failure cases, an artificial pacemaker or organ transplant may be needed.

Weve seen some horrendous things that could have been dealt with a lot sooner.

Treatment involves looking after the other arteries because you cant afford to lose any more heart muscle with another heart attack.If we get them from their home to hospital within two to three hours then we have a very high chance of salvaging their heart muscle and keeping them alive. If its five to six hours after the onset of the heart attack, even if you unblock the artery, the amount thats salvaged is much less, says Wong.

There have been too many preventable heart attack deaths from patients who stayed away from hospital during the pandemic, Wong says. Weve seen some horrendous things that could have been dealt with a lot sooner, he says. Having ambulances ramped outside emergency rooms is a particular concern in heart attack cases.

When treatment is swift, you can go on to lead a normal life, with medication and lifestyle adjustments to help keep your arteries open. Still, its estimated that about 20 per cent of heart attack patients will be hospitalised with a second one within five years, a reality that Wong says can make people feel very anxious.

Its why cardiac rehabilitation is so important as it involves structured physical activity and education on lifestyle and medicines, Jennings says, urging people to speak to their doctor about enrolling in a program or use the Heart Foundations directory to find one.

The heart does age and wear out eventually, Wong says. Sometimes I have to say to patients, Its more a case of youve had too many birthdays. That said, a heart attack is eminently preventable, Jennings says, particularly under the age of 80. The goal is to slow the rate at which the coronary arteries are narrowing and stiffening.

First, its good to understand what we can control. We cant change our age nor our genetics, both of which are unavoidable factors in our risk of heart disease. Some people can do all the wrong things [for their health] and never have a heart problem. Other people barely infringe and suffer from heart disease, says Jennings.

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Some people have a family history of heart disease. Wong starts to treat such patients about five years before their close relative who had heart trouble started having issues. Some people might have naturally high cholesterol (called familial hypercholesterolemia). Here, heart complications tend to occur in someones 20s.

Health issues such as high cholesterol or blood pressure have effective medications. But whatever your genetic background, youll still be better off with a better lifestyle, so never give up, Jennings says. Poor nutrition, low physical activity, drinking alcohol, smoking and being overweight: these are all major risk factors that can be improved. A 2019 study of more than 26,000 people aged over 18 found that a healthy lifestyle was linked to a 44 per cent lower risk of coronary heart disease.

This might sound a bit airy-fairy, but I say thank you to my heart every day. I am in absolute awe of my heart.

Sometimes people become scared of putting pressure on their heart with exercise but Jennings urges people to ditch the fear. Theres nothing better you can do for your heart than being physically active, he says. Sensible exercise, where people build up a program and get fit, is one of the healthiest things.

The Mediterranean diet remains the gold standard for a healthy heart, he says, and instead of focusing on food components, such as fat and cholesterol, there is increasing emphasis on healthy food combinations so, lots of fruit and vegetables, olive oil, fish and chicken because people eat food, not polyunsaturated fat .

Kath Moorby had many risk factors, from family history to years of weight struggles. Before her heart attack she had lost 100 kilograms but her diet remained unhealthy, and she was smoking 50 cigarettes a day. What you do in your younger years comes back to bite you on the bum, Moorby says. Today, she eats better, walks, doesnt drink and no longer smokes.

While coronary heart disease kills more Australians than any cancer (lung cancer is the fourth-leading cause of death in men and women), Jennings observes that cancer tends to be more feared in society, not least because people fade away in front of us, whereas with a heart attack [often] theyre just gone [suddenly].

He says there is a degree of unfair blame that is heaped on heart disease patients too. Its not necessarily their fault if theyre overweight or have undetected risk factors. We just need to help them a bit more, he says.

Andrew van Vloten, who had two heart attacks, urges people to learn about their bodies and their limits and take any heart disease risk factors seriously by visiting a doctor. Today, hes a proud 10-kilometre race finisher, and he connects with his heart through meditation. This might sound a bit airy-fairy, but I say thank you to my heart every day, van Vloten says. I am in absolute awe of my heart, the function it does and what its capable of doing.

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Whats a heart attack? How can you tell if youre on the edge of one? - Sydney Morning Herald

Osteoarthritis (OA) is the most common type of arthritis[1], and it is characterized by a progressive loss of articular cartilage, subchondral bone edema, sclerosis, synovitis, and marginal osteophyte formation. Pain, stiffness, and a restriction in joint movement are the most common symptoms whose severity varies. However, the condition gradually worsens over time and often results in significant functional impairment and reduced quality of life[2,3]. It was anticipated to become the fourth leading cause of disability by 2020[1,4,5], posing a significant socioeconomic burden impacting developed countries' gross domestic product[1,6]. Knee osteoarthritis (KOA) accounts for 85 percent of the global burden of OA and affects 19% of adults over 45-year-old and 37% of people over 60. KOA produces significant pain and physical impairment, lowering the quality of life and ranking as the eleventh leading cause of global disability. The average annual total expense per KOA patient is over US$15 000, resulting in total healthcare expenditure of nearly US$34 billion. Given population aging and the rise in obesity, KOA healthcare expenses are expected to quadruple by 2040[7]. It is necessary to develop sufficient medicines capable of slowing the progression of the disease and, as a result, preventing the loss of articular function and joint replacement. To provide more effective therapies, current conservative choices such as exercise and physiotherapy and weight loss with analgesics and naturally occurring substances should be integrated[1,8]. Developing effective conservative methods would be especially important for treating young people with early OA because their more active and physically demanding lifestyle negatively correlates with prosthetic implant survival[1,9].

The main treatment in the clinic is non-steroidal anti-inflammatory drugs (NSAIDs), which are recommended for all patients except those having surgical treatment in the American Academy of Orthopaedic Surgeons (AAOS) clinical practice recommendations for KOA treatment[10-12]. However, long-term usage of these treatments will cause major adverse reactions in patients, such as gastrointestinal ulcers, digestive system hemorrhage, and cardiovascular and cerebrovascular side effects, regardless of the toxicity of the drugs themselves[10,13]. Intra-articular injections of HA, platelet-rich plasma (PRP), or corticosteroids (CC) are also clinical possibilities, but their efficacy and the prevalence of side effects are still debated[10,14,15].

MSCs, be a possible treatment option for KOA[16-20]. MSCs, also called MPCs, secrete various cytokines that modulate an anti-inflammatory milieu in the OA joint, giving them immunomodulatory characteristics[18,21]. They may also have a unique ability to induce the growth of new cartilage-like cells in vitro[17,18,22], as improvements in cartilage morphology have been found in some situations[23-26]. These characteristics make them a suitable candidate for use in knee cartilage repair[27-32]. For OA treatment, orthobiologics injections containing MSCs as effector cells have recently been used. Because of their accessibility, bone marrow (BM) and adipose tissue (AD) have traditionally been the most used autologous tissue sources for orthopedic usage. In several studies, the use of autologous orthobiologics treatments in the treatment of OA is safe, with an extensive multicenter prospective analysis revealing no higher risk of neoplasia[33,34].

MSCs treatment looks to be safe based on published clinical study results. There were no significant side effects other than transitory fever in a comprehensive systematic review and meta-analysis of trials involving intravascular delivery of autologous or allogeneic expanded MSCs treatments (totaling over 1000 participants)[35,36]. A systematic evaluation of clinical trials involving intra-articular autologous expanded MSCs therapy that included 844 procedures. They had a mean follow-up of 21 months and found no link between infection, cancer, or death[35,37].

As a result, we undertook this study to examine all current high-quality information on the therapeutic efficacy and safety of MSCs in the treatment of KOA qualitatively and quantitatively. This is crucial, and the study's findings will give evidence and recommendations for the promotion and deployment of MSCs therapy in clinical practice.

We developed and implemented the study according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) system[38], the review's preferred reporting items.

Database

On December 30, 2021, we began our research using online libraries as a database. For our data gathering, we used PubMed, the Cochrane Library, and PMC.

Search Strategy

We included studies related to KOA, MSCs, and intra-articular injection. Our keywords and medical subject heading (MeSH) search strategies included knee, osteoarthritis, mesenchymal stem cells, intra-articular, and injection. The main MeSH terms used were: ("injections, intra articular"[MeSH Terms] OR ("injections"[All Fields] AND "intra articular"[All Fields]) OR "intra-articular injections"[All Fields] OR ("intra"[All Fields] AND "articular"[All Fields] AND "injection"[All Fields]) OR "intra articular injection"[All Fields]) AND ("mesenchymal stem cells"[MeSH Terms] OR ("mesenchymal"[All Fields] AND "stem"[All Fields] AND "cells"[All Fields]) OR "mesenchymal stem cells"[All Fields]) AND ("osteoarthritis, knee"[MeSH Terms] OR ("osteoarthritis"[All Fields] AND "knee"[All Fields]) OR "knee osteoarthritis"[All Fields] OR ("knee"[All Fields] AND "osteoarthritis"[All Fields])) and Knee Osteoarthritis, Mesenchymal Stem Cells, Intra-articular Injections. MeSH terms carried out a further supplementary search with free words. In addition, to prevent eliminating papers that satisfied the inclusion criteria, we searched retrieved studies that were cited.

Inclusion Criteria

We included RCTs and clinical trial studies conducted between 2017-and 2021, with complete free texts in the English language from all countries. Also, men and women aged 18 years or older with osteoarthritis in their knees and the severity of their osteoarthritis are shown in KL grade.

Exclusion Criteria

We excluded studies before the last five years, not in English, that included animals, HA, PRP, arthroscopy, ultrasound waves, and combination treatment in the intervention, other than knee joints like shoulder and hip.

Quality Assessment Tools

Two authors, S.S and S.V, independently assessed the study's overall quality and risk of bias by using the Cochrane Collaboration risk-of-bias tool for the RCTs and Newcastle Ottawa Scale (NOS) for the clinical trials. The Cochrane Collaboration risk-of-bias tool included random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. Each included RCT was rated as having a low, unclear, or high risk of bias based on these factors. The following are the contents for the NOS, including selection, comparability, and outcome. According to these items, each included clinical trial was scored as good, fair, and poor quality.

Data Extraction

Two writers, S.S and S.V, worked independently to extract data using a standardized manner. Disagreements that arose during the procedure were resolved through debate between the two writers or contact with a third author, just as they were with the inclusion of literature into the study. The following were the contents of the data extraction form: the first author's name, the year of publication, the sample size, basic patient information (age, male-to-female ratio, body mass index (BMI)), osteoarthritis grading KL grade, donor source (autogenous/allogeneic), cell processing, culture, and harvesting, number of cells, immunophenotype, intervention, and control situation, follow-up, and outcome clinical effectiveness and safety were among the outcomes.

Literature Search

Using the literature search, we discovered 78 relevant papers. After eliminating duplicates and screening titles and abstracts, 50 articles were excluded. The remaining 18 articles were subjected to a full-text review, with eight being excluded, as shown in figure1.

Characteristics of the Included Studies

A total of six RCTs (577 participants)[2,7,17,18,32,35], including one study which had a pilot study, commenced in November and completed in June 2021, where recruitment commenced in January and August 2021 and will be finished by December 2024[7]. Four clinical trial studies, including three prospective[16,23,32], and one retrospective[33]clinical trial, were included in this systematic review. Publication intervals for all 10 were from 2017 to 2021[7]. All studies used autologous MSCs except two studies[2,7], which used allogeneic MSCs. Five studies[2,17,18,35,39], used AD-MSCs two studies[23,32], used BM-MSCs, one study[16], used BMA, one study[33], used both concentrations BMAC and MFATand one study[7], used multipotent MSCs. A placebo was utilized as a control group[2,39]. For one study, NS was used as the control group[7]; for one trial, HA was used as the control group[17], In one study's control group, cautious management was adopted[35], and five of the investigations[16,18,23,32,33], were uncontrolled. Furthermore, four trials[2,16,17,35]were monitored for a year, three trials[7,23,32]were monitored for 24 months, and two trials[33,39]were followed for six months after they were completed, and one study[18], had a 48-weeks follow-up period. Table1illustrates the features of the 10 articles that were featured.

Risk of Bias Assessment

Figure2shows the results of the risk of bias evaluation for six studies[2,7,17,18,35,39], while table2shows the results of the NOS for four studies[16,23,32,33]. Lee et al.[39], although relevant images were drawn, we could not retrieve the original data and conduct the combined statistics; hence this study was classified as having a high risk of reporting bias. Freitag et al. and Kuah et al. incomplete data on overall WOMAC scores and subscales (pain, stiffness, and function) were also given, and one or more of these characteristics may have been missing. As a result, attrition bias was found to be considered a risk in these two investigations[2,35]. Freitag et al. performed BM or subcutaneous tissue extraction only in the intervention group. Even though moral restraint precluded the same measures from being used in the control group, this study was classified as having a high risk of detection and performance bias[35].

Outcomes

Knee Injury and Osteoarthritis Outcome Score (KOOS): A total of seven studies[7,16,23,32,33,35,39]reported KOOS[40]at baseline and final follow-up in the intervention and the control groups, including 650 patients. Three studies[7,23,32] were followed up for 24 months, two studies[16,35]were followed up for 12 months, and two studies[33,39]were followed up for six months. Normalized KOOS was used to measure positive changes in all five primary areas, and all were significantly better at six, 12, and 24-months post first injection[32]. Significant improvements in Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) scores were observed over time (F (4,12) =12.29, p<0.001) in a cohort. Following the procedure, clinical significance was accomplished at three, six, and 12-months following the procedure[16]. As evaluated by normalized KOOS, table3demonstrates the favorable changes in all five essential categories. All were much improved at six, 12, and 24 months after the first treatment[32]. Using all sample time points, the Sport Score and quality of life (QOL) score were nominally linked with an unadjusted p-value of 0.031 and 0.046, respectively[23].

Magnetic Resonance Imaging (MRI) Evaluation

A total of eight studies reported MRI evaluation at baseline and follow-up in the groups, including 659 patients[2,7,17,18,23,32,33,39]. Three studies[7,23,32]were followed for a total of 24 months, for 12 months, two studies[2,17]were followed up on, and two studies[33,39]were followed up for six months after they were completed, and one study[18], had a 48-weeks follow-up period. The transformation of the central medial femorotibial compartment (cMFTC) cartilage thickness[41]for a 24-month was 0.32 mm (SD=0.40) for those who have narrowed medial tibiofemoral joint and maintained knee pain at baseline in comparison to the control neither of which radiographic nor pain development (0.12mm, SD=0.28)[7,42]. 67 percent of patients had progressed cartilage degeneration within the control group, with another 56 percent having extended osteophyte formation. Only 30% of individuals saw additional cartilage loss in the one-injection group, whereas 50% experienced osteophyte development advancement at 12 months. In the two-injection group, 89 percent of participants had cartilage improvement or no progression in cartilage loss, indicating that OA had stabilized, as seen by 89 percent of subjects having no progression in osteophyte formation[35]. The size of the cartilage defect in the MSCs group did not change substantially on MRI at six months (p =.5803), but the size of the cartilage defect in the control group grew significantly (p =.0049). Furthermore, the change in cartilage defect following the injection was significantly different between the two groups (p =.0051)[39]. Using the WORMS technique, the low-dose group had a mean change from baseline of -0.36 and -0.86 in both the left and right knees at week 48. Furthermore, the mean changes in total cartilage volume, knee femur end cartilage volume and knee patellar cartilage volume in the low-dose group were 54.58, 38.63, and 39.69 mm, respectively. The knee tibial end cartilage volume and knee cartilage volume in the medium-dose group improved by 243.32 and 34.44 mm, respectively. Increases of -0.42 and 122.92 mm in the left knee WORMS and knee femur end cartilage volume were reported in the high-dose group[18].

Two bilateral intra-articular knee injections, three weeks apart (18-20 days), were used in this preclinical study with AlloJoin. Because the high prevalence of bilateral KOA in the treatment population was investigated[18,43,44]. MRI showed no significant change in cartilage thickness after six months. As indicated in Table4, there was a considerable improvement in knee cartilage thickness in the femoral and tibia plates after 12 months[32]. Time 2 (T2) scores in the patella region increased by a negligible amount (p =.055 for a two-sided test, nonadjusted). T2 changes (from baseline to 12 months) did not differ across the one, 10, or 50 million BM-MSCs cohorts[23]. The 50 million BM-MSCs doses (effect estimate [B] = 1.828, p =.002) maintained synovitis at lower levels than the one million BM-MSCs dose, according to statistical analysis of the effects of dose adjusted for both time and baseline levels of synovitis[23]. We found a decrease in pro-inflammatory monocytes/macrophages in synovial fluid three months after MSCs infusion, suggesting a potential mechanism of action. We do not see statistical significance relative to baseline levels (p =.062) because of the small number of patients who presented synovial fluid at baseline and three months after MSC infusion (n = 5). However, this downregulation suggests a potential mechanism of action of MSCs in the arthritic joint[23].

Visual Analogue Scale (VAS)

A total of five studies[2,17,18,33,39]reported VAS evaluation at baseline and follow-up in the groups, including 194 patients. Two studies[2,17]were followed up for 12 months, two studies[33,39]were followed up for six months, and one study[18]was followed up for 48 weeks. VAS32[7], (P < .00001)[10], (p 0.005) in Progenza (PRG) combined group[2]. In the MSCs group exclusively, the VAS for knee discomfort dropped dramatically from 6.8 0.6 to 3.4 1.5 (p.001)[39]. Our VAS data confirmed clinical improvement with these cell injections, as seen by the study's reported VAS minimal clinical improvement differences (MCID) score of 30.0 mm[18,45,46].

Western Ontario, and McMaster Universities Osteoarthritis Index (WOMAC)

A total of six studies[2,17,18,23,35,39]reported WOMAC[47], evaluation at baseline, and follow-up in the groups, including 160 patients. Three studies[2,17,35]were tracked for 12 a year, one trial[23]was monitored for 24 months, one study[18]had a 48-weeks follow-up period, and for six months, one trial[39]was followed. (All P values were less than .05)[10]. Also, compared to the HA group, significantly more individuals had a 50% improvement in WOMAC, and after 12 months, the Re-Join group had a 70% improvement rate, indicating that more patients were improving[17].

At six months after injection, a single injection of AD-MSCs resulted in a 55 percent reduction in the WOMAC total score, a 59 percent reduction in the WOMAC pain score, a 54 percent reduction in the WOMAC stiffness score, and a 54 percent reduction in the WOMAC physical function score[39]. According to a study in previous research[24,48-50], clinical outcomes improved six months following MSCs injection. The findings of this investigation support this. Furthermore, similar to earlier research[49,50], even six months following injection, the clinical outcomes were still good. This finding implies that with a single intra-articular MSCs injection, symptom alleviation can be sustained for up to six months[39]. Improvements in short form 36 (SF-36), -23.71 in WOMAC total, -17.14 in WOMAC-function, -2.29 in WOMAC stiffness, and -4.29 in WOMAC-pain were seen in the low-dose cohort. Improvements in left knee VAS were -2.25, right knee VAS was -2.13, WOMAC-total was -16.50, WOMAC-function was -11.88, WOMAC-stiffness was -1.71, and WOMAC-pain was -3.25 in the medium-dose cohort. The high-dose cohort observed statistically significant improvements in the left knee VAS of -1.36 and the right knee VAS of -2.07[18]. The MCID averages for the WOMAC with KOA have been published[51]. The WOMAC functional score ranges between 9.1 to 19.9 mm, indicating that the WOMAC scores in this trial indicated considerable clinical improvement for the overall WOMAC functional (17.1) for both the left and right knees after 48 weeks for two of the doses[18,52-55].

Adverse Events (AEs)

A total of four studies[7,16,17,32]reported AEs evaluation at baseline and follow-up in the groups, including 550 patients. Two studies[7,32]were followed up for 24 months, and the others[16,17]were followed up for 12 months. Patient satisfaction was high (range: 8.12.1-8.81.9). All the patients said they would recommend the treatment to a friend, and 85 percent said they would do it again[16]. In the MSCs group, 10 (83%) patients experienced AEs, compared to seven (58%) individuals in the control group. No significant AEs or grade 4 or 5 AEs on the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale. All the grade 3 AEs on the NCI-CTCAE scale were arthralgia, which completely disappeared within three days[39,56]. In the low-, middle-and high-dose groups, the incidence of AEs was 71.42 percent (5/7), 87.50 percent (7/8), and 100 percent (7/7), correspondingly[18].

We evaluated the clinical efficacy and safety of intra-articular injection of MSCs in this study by thoroughly analyzing six RCTs and four clinical trials. The study's first strength is its comprehensiveness, a compilation of all current high-quality studies. Second, we assessed the included studies' cell adherence, cell immunophenotype, and cell differentiation ability using the MSC criteria established by the Mesenchymal Stem Cell Committee of the International Society for Cell Therapy (ISCT), and discovered that half of them meet the minimum requirements[16,18,23,35,39], as shown in table1. Third, it contains tight inclusion and exclusion rules. Concurrent therapy studies, such as HA and PRP were omitted. The addition of newly incorporated research of AT and BM sources, we believe, is what has led to the divergent results. This is one of the reasons we are so adamant about completing this research. Compared to the control group, the MSCs group showed a considerable increase in cartilage volume.

The selection of the appropriate donor source and the optimal dose has become an essential issue due to the extensive research into MSCstherapy. BM, AT, placenta, and umbilical cord are among the most popular donor sources for MSCs in clinical research. Initially, people preferred to cultivate and expand BM-MSCs. Later research discovered that AT was more accessible than BM, had a simpler isolation technique, a larger yield, and the same chondrogenic capacity[10,57,58].

A reduction in pain is connected to the ability of cells to release bioactive chemicals. These elements are hypothesized to change the inflammatory milieu in the joint from pro-inflammatory to anti-inflammatory. PRG includes a high concentration of these bioactive substances in the cell culture supernatant, unlike other cell therapies. PRG may decrease the progression of OA based on the favorable cartilage outcomes from preclinical and clinical investigations. Many studies have found that beneficial effects are primarily apparent in the lateral tibial region. Although OA affects the entire joint, it has been hypothesized that the medial tibiofemoral region is more severely damaged than the lateral tibiofemoral region. As a result, because the medial tibiofemoral region is later, there may be fewer opportunities to demonstrate progress[2].

MPCs tagged with fluorescent dye lasted locally in the joint for up to 10 weeks in preclinical rat studies before becoming undetectable[18,59]. Furthermore, the serious adverse events (SAEs) contradict all preclinical animal investigations that revealed no evidence of systemic exposure[18,59-61]. In addition, earlier research has shown that Re-Join is beneficial in rabbit and sheep models of OA[17,60,61]. The repair of osteoarthritis in rabbits and goats appears to be mediated by paracrine effects involving the stimulation of endogenous repair systems[26,32]. In a systematic evaluation of MSCs therapies, Lalu et al. found no significant side effects[23,62,63]. Following the aspiration of BM, there were no systemic side effects observed, and there were no issues that were noted[23]. Therefore, no individuals dropped out of the study[2].

Our findings show that there are statistically significant improvements in pain and function[2,7,10,16-18,33,35]. The average percentage of patients who have passed the Patient-Acceptable Symptom State (PASS)[64]the threshold was 35% in the placebo cohort(ranging from 33.1 to 35.5) and 48% in the intervention cohorts (varying between 42.2% to 56.1%)[7,65,66]. There were also decreases in present, typical, best, and worst numerical rating scale (NRS) pain[67], scores statistically significant over time (F(4,12)=14.5, p<0.001; F(4,12)=17.5, p<0.001; F(4,12)=2.9, p=0.003; and F(4,12)=35.5, p<0.001, respectively)[16]. Also, NRS pain in both the single and two injection protocol treatment groups, when compared to baseline, within-group improvement was statistically significant (0.05) at all time intervals[35]. Therefore, we found that all statistical tests for pain and functional outcome measures (n = 21) had a mean power of 0.877 15 SD[35]. The NPRS improved by 69 percent from baseline to the last follow-up at 12 months in both therapy groups. In comparison, arthroscopic debridement resulted in a 14 percent improvement in pain scores after 12 months, while a prescribed exercise regimen resulted in a 12 percent improvement in pain scores[35,68,69]. The range of motion in the MSCs group improved considerably from 127.9 10.3 to 134.6 12.5 at six months after injection (p =.0299)[39]. When these established MCID values were applied at 48 weeks, there was a reduction in pain and an improvement in knee function; however, due to the small number of participants included in this pilot investigation, these findings should be regarded with caution[18].

In addition, they discovered a link between the number of cells injected and pain relief[33]. Furthermore, two RCTs were recently reported, revealing significant improvements in pain and function in KOA patients after injection of autologous AD-MSCs versus controls[33]. MSCs generated from autologous BM showed a significant increase in clinical ratings[33,39]. Because the researchers differ in study design, cell type, supplementary therapy, and rehabilitation methods, it is difficult to determine the true differences in intra-articular injections of BM-MSCs and AD-MSCs[39].

Data reveal that one or more outcomes, such as KOOS pain, have improved statistically significantly[23,32,35], symptoms, SF-36[18], VAS[2,10,16,18,33,39], and QOL scores[17,23,33], as well as WOMAC stiffness[2,10,16-18,23,33,35,39]. NPRS improved[16,35], from baseline to final follow-up at 12 months, by a percentage of 69 percent previous clinical trials have shown that intra-articular MSCs treatment can slow the course of OA[35]. All symptoms decreased dramatically, resulting in a considerable improvement in the quality of life of these grade 2 to 4 KOA patients. There is also evidence of safety. However, more research is required. Another concern is that most research focuses on short-term safety rather than long-term results[32]. Starting three months after the procedure, KOOS-JR scores improved dramatically, with clinically meaningful improvements lasting 12 months[16]. Within 48 weeks of follow-up, MCID scores for SF-36 are approximately 10%, which this study's data has surpassed[18,53,70,71]. Both groups improved significantly in Emory Quality of Life (EQOL), VAS, and all KOOS indicators pre-and post-procedure (p < .001)[33]. During follow-up, the two treatment groups' EQOL ratings altered in similar ways (similar temporal patterns across time) (p =0.98, test for interaction between time on study and treatment group)[33].

We report putative chondroprotective benefits and decreased synovial inflammation, with the 50 million cell dosage potentially being more beneficial. However, when compared to the 50 million and/or 10 million BM-MSC dosages, serum carboxy-terminus of the three-quarter peptide from cleavage of C I and C II (C1, C2), urine type II collagen cleavage neoepitope (C2C), and C-telopeptide of type II collagen (CTX-II) all increased significantly, suggesting a chondroprotective MSCs dose effect, as previously described[23]. Furthermore, exploratory MRI analyses of average cartilage volumes and average WORMS from baseline at week 48 revealed no change in the medium-dose (2*107 cells) and high-dose (5*107 cells) groups but an improvement in the low-dose AlloJoin (1*107 cells) group[18]. Over radiography x-rays, MRI assessments offered a more accurate picture of articular cartilage deterioration and change in location of the menisci[18,72]. Because MOAKS[73]is a semi-quantitative metric, the MRI analysis is limited[18]. Furthermore, MOAKs analysis demonstrating effective stabilization despite continuous bone marrow lesions (BMLs)contrasts with previous research that has found a link between BMLs and OA progression[35].

Because Orozco et al. showed a consistent improvement in cartilage quality during a two-year follow-up period from the baseline, we expect cartilage improvement in our series over a longer follow-up time[39,48]. Our research also saw increased cartilage volume and quality[2,17,18,23,32,39]. Furthermore, an MRI examination at 48 weeks revealed no signs of ectopic bone development[18]. Intra-articular injections of Re-Join were found to enhance cartilage volume, with a significant rise 12 months after injection, suggesting that this could be a viable therapeutic intervention and cartilage regeneration for OA patients[17].

We believe that the subsequent trials should be greater[23]. The following trials should, in our opinion, be larger[18]and also look at the MSCs dose and the MSCs source. The safety of allogeneic MSCs for KOA must be established[23,32,39]. The usage of allogenic MSCs can be standardized, the dose can be more precisely regulated, and cell variability may be minimized. We should also examine the efficacy of BM and AD-derived orthobiologics treatments to develop a reliable judgment on which is the better choice for treating KOA[33]. MSCs, we feel, has the potential to be a definitive treatment for KOA[32]. It is also critical to distinguish the findings of this study from those of previous studies that used more various cell-based products, such as stromal vascular fraction[35].

This research has several limitations. The results should be treated with care first and foremost. We did our utmost to avoid simultaneous surgical treatment affecting efficacy. Second, all the studies we looked at used intra-articular injections. MSCs implantation by open or arthroscopic surgery has been proven to be more conducive to cartilage repair in several studies. While MSCs transplantation on a scaffold may help rebuild the anterior cruciate ligament and meniscus[10]. Third, four of our studies[16,23,32,33], were not RCTs. Fourth, we included three studies[23,33,39]that included KL grade 4 KOA patients. We do not know if the disease can be slowed or even reversed at this point in the disease's progression, especially using autologous-derived MSCs. Furthermore, as the human body ages, MSCs' ability to self-renew and differentiate decreases; particularly, the potential of MSCs in individuals with OA is lower than that of healthy persons[10,17,23,33,35].

Read more:
Safety and Efficacy of Injecting Mesenchymal Stem Cells Into a Human Knee Joint To Treat Osteoarthritis: A Systematic Review - Cureus

Dr. Sara Vasconcelos in the laboratory at Toronto General Hospital on May 11.Christopher Katsarov/The Globe and Mail

When Sara Vasconcelos talks about her work, it sounds as if shes in the restoration business. But instead of repairing damaged buildings, the researcher at Torontos University Health Network wants to fix damaged hearts by using stem cells to rebuild cardiovascular tissue.

Now, Dr. Vasconcelos is one step closer to achieving that goal with a $3-million grant from the Stem Cell Network, a Canadian research funding organization. Her effort is one of 32 projects across the country that rose to the top in a competition for in the largest outlay of federal funding for regenerative medicine in 20 years.

On Thursday, the Ottawa-based network announced a total of $19.5-million in awards, which together with matching funds from various partners, will translate into $42-million for research and clinical trials over the next three years. The funding will enable the work of more than 400 scientists, clinicians and trainees, the organization said.

Its a big step, said Dr. Vasconcelos, who said she will use her award to build on preliminary findings obtained using rats. She will next work with pig hearts, which offer a much closer analogue to the human organ.

While doing so, she also hopes to overcome a barrier that has stood in the path of those who are trying to repair hearts using cardiomyocytes heart tissue cells that are grown from embryonic stem cells. The problem is that the replacement cells wither away if they are not nourished and kept alive by blood vessels.

As part of her project Dr. Vasconcelos aims to use a technique in which small sections of microscopic blood vessels are harvested from human fat and implanted along with the heart cells.

The microvessels that are like Lego pieces, she said. You can put a whole bunch of them in with the stem cell-derived cardiomyocytes and they will connect to each other and connect to the host vessels that carry blood.

With her grant secured, Dr. Vasconcelos said she is assembling the team that will test the method on pig hearts later this year. Ultimately, her goal is to develop the technique into a therapy that can restore cardiac function in human patients following a heart attack, she said.

Among the other projects to win funding are some that are already heading for clinical studies. That includes a large study led by Guy Sauvageau, a hematologist at Maisonneuve-Rosemont Hospital in Montreal, that involves developing engineered blood stem cells to treat leukemia.

Working with a group of clinical sites in the U.S., Dr. Sauvageau and his team have already had success at treating patients with leukemia who relapse. The new project will involve introducing genetical engineered stem cells into people who are better able to withstand cancer treatment and facilitate recovery.

Between 10,000 and 20,000 patients a year would benefit from this kind of therapy, Dr. Sauvageau said.

In the future, he added, the study could open the door to teaching the body to continually produce and replenish its own cancer-killing immune cells rather than having those cells created externally and infused in a form of treatment know as CAR T-cell therapy.

As part of another of the funded projects, David Thompson at the Vancouver Coastal Health Research Institute will conduct clinical trials for one of the worlds first genetically engineered cell replacement therapies for type 1 diabetes.

Dr. Sara Vasconcelos points to an image of vascular tissue in the laboratory at Toronto General Hospital where they engineer cell and tissue regeneration.Christopher Katsarov/The Globe and Mail

The diversity of the projects highlights the increasing prominence of stem cells in multiple domains of health research, an area where Canada has a long track record of success ever since University of Toronto researchers James Till and Ernest McCullough established the existence of stem cells cells which can differentiate into more specialized types in bone marrow in 1961.

Tania Bubela, dean of health sciences at Simon Fraser University in Burnaby, B.C., said the kind of funding the Stem Cell Network provides helps bridge a crucial gap between fundamental laboratory research and proven therapies for patients.

What weve realized over time is that where you get public sector investments to close the funding gap is exactly in that translational space from preclinical into early stage clinical trials, Dr. Bubela said. Once you have that proof that things are going to work and that they can be taken up by the health system, thats when venture capital starts to get interested.

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Heart, cancer and diabetes projects among winners of funding boost for stem cell therapies - The Globe and Mail

Lab animalshave been an essential part of life-altering and lifesaving scientific research and discovery. But a growing number of scientists are calling for an end to their use, and pushing for new methods that can better replicate human biology instead.

Among them is biomedical researcher Dr. Charu Chandrasekera. She'sthe founder and executive director of the Canadian Centre for Alternatives to Animal Methods at the University of Windsor. Here is part of her conversation with Quirks & Quarks host Bob McDonald.

Animal testing historically has been considered a regrettable necessity in the quest to save human lives. Why do you think this is not the case?

Animals have played an integral role in science over the past century or more, to the point where we have made them the gold standard for human biology. And therein lies the problem.

Over 90 per centof drugs tested to be safe and effective in animals, fail in human clinical trials. And even the ones that make it through, they can still be withdrawn or receiveblack box warnings due to unpredicted side effects in humans. And it's not just the drugs that fail, but the drugs that we missed,like the drugs that never made it to human clinical trials because they had some irrelevant side effects in animals. They could very well been safe in humans.So we've likely missed out on many life saving, history altering medications.

Why would a drug work in an animal but not in a human?

Well, there's a very simple answer to that. We humans, we are not 70-kilogram versionsof mice, rats, guinea pigs, rabbits, cats, dogs, sheep or monkeys. We're human. We're separated by hundreds of millions of years of evolution from some of these laboratory animal species.

And it's not only just the species' differences, but there are also so many issues with the way we conduct this research. We have to induce disease by either doing surgical modifications, giving them a high-fat diet. So dietary modifications, genetic modifications, take out a gene, put in a gene, or chemically destroy their pancreas, for example, to create diabetic models. So when you're doing these experimental modifications in these animals, you're really not recreating the human disease. You are creating a version of a human disease.

What motivated you to go from doing animal research in your lab to trying to end the practice altogether?

It was the scientific failures combined with the ethical standards that I was not happy with. So I worked with animal models of heart failure. And while I was doing all these studies, my dad actually had a heart attack and he required quadruple bypass surgery. And while I was with him at the Halifax Heart Centre, I thought to myself, is the research that I'm doing going to truly help humans like my father and everybody else in this ward?

A few weeks later, when I came back to the lab, I ran into this veteran cardiovascular researcher, and he had worked on receptors similar to the ones that I was working on. And I just looked at him and I said, "Do you think these receptors were activated in my dad's heart during his heart attack?" And his response was, "How the hell would I know? We've never looked at this in the human heart."And for me, that day, it was a profound realization. It was almost like an epiphany. What am I doing this for?

Those are the reasons why we should end animal research. Let's explore some of the solutions. What are some of the alternative methods to animals in research that are being developed?

Recreating human biology in a petri dish is no easy feat. There's no single magical method that can replace all animal testing tomorrow morning. It's really all about context of use, fit for purpose. What is the biological question you're trying to answer, and in what context, and how best can we address that?

So we can use human cells and tissues from cadavers and surgical remains. We can take a diseased heart removed during transplant surgery and bring it back to life in the lab, make it beat again, infused with drugs to study cardiac physiology and cardiac toxicity. We can take just a single human cell and obtain hundreds of data points on human DNA and RNA through multiomics studies. We can engineer human tissue, create miniature organ models like organoids to recapitulated complex diseases using stem cell technologies. The field is just exploding.

Can you give me a list of some of the projects that you're working on at your centreright now?

We currently have liver, gut, kidney, lung and blood brain barrier models in development. And we have a number of projects that incorporate these tissues in different configurations to create disease in a dish, and toxicity on a chip. One of the first disease models we're creating is diabetes in a dish, and we're also doing Alzheimer's in a dish. We actually have a project designed specifically to reduce and replace toxicity testing in dogs. And we even have an eco-toxicology project where we're using fish lines to replace toxicity testing on live fish.

This is all based on evidence now. So for some of these methods that we have, we are already seeing that they are able to recapitulate these human responses. We can actually look at the data that we get from using these new technologies and compare them against existing data. But we are also seeing things like new data where we're going back and reevaluating these old drugs that failed in one system and then putting them through a human biology based system. And we're seeing that they are able to predict human biology better.

How hopeful are you that we can make this shift away from using animals in scientific research?

I'm actually very hopeful that we will be able to shift away from this animal-centred paradigm to one where human biology is the gold standard and humans are the quintessential animal model. There are scientific, innovative financial and legislative efforts happening around the world to make this happen.

The goal really is to reduce as much as possible at this point. And even if we needed to use animals, could they become the last resort that you are only using, you know, five rats, for example, for a procedure that required 400 rats before?So because of all of these efforts happening globally, I'm very hopeful.

Produced by Amanda Buckiewicz. This interview has been edited for length and clarity.

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Meet the Canadian researcher determined to take the animals out of lab testing - CBC.ca

Worlds 1st Focused Ultrasound Cancer Immunotherapy Center LaunchedUVA Health and the Charlottesville-based Focused Ultrasound Center today announced the launch of theFocused Ultrasound Cancer Immunotherapy Center, the worlds first center dedicated specifically to advancing a focused ultrasound and cancer immunotherapy treatment approach that could revolutionize 21st-century cancer care.

A Study by the Gwangju Institute of Science and Technology Investigates Mercury Contamination in Freshwater Lakes in KoreaDuring the 1950s and 1960s, Minamata Bay in Japan was the site of widespread mercury poisoning caused by the consumption of fish containing methylmercurya toxic form of mercury that is synthesized when bacteria react with mercury released in water.

Researchers identify possible new target to treat newborns suffering from lack of oxygen or blood flow in the brainThe condition, known as hypoxic-ischemic encephalopathy (HIE), can result in severe brain damage, which is why researchers at theCase Western Reserve University School of Medicineand UH Rainbow Babies & Childrens Hospital (UH Rainbow) are studying the condition to evaluate how HIE is treated and develop new, more effective options.

Should You Give Your Child Opioids for Post-Operative Pain Management?Routine head and neck procedures, such as removal of tonsils and adenoids and the placement of ear tubes, may cause moderate to severe pain in pediatric patients.

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Some Shunts Used After Epilepsy Surgery May Risk Chronic HeadachesSurgeons who observe persistent fluid buildup after disconnecting epileptic and healthy brain areas should think twice before installing low-pressure nonprogrammable drainage shunts, according to a study coauthored by Rutgers pediatric and epilepsy neurosurgeonYasunori Nagahamathat found chronic headaches could result from these procedures.

Re-defining the selection of surgical procedure in sufferers with tuberous sclerosis complicatedBy illustrating a number of instances of tuberous sclerosis in sufferers whove undergone surgical resection with seizure-free outcomes, researchers have recognized components that decide choice of sufferers for profitable surgical procedure.

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Robotic therapy: A new effective treatment for chronic stroke rehabilitationA study led by Dr. Takashi Takebayashi and published in the journal Stroke suggests continuing therapy for chronic stroke patients is still beneficial while suggesting a radical alternative.

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Toxoplasmosis: propagation of parasite in host cell stoppedA new method blocks the protein regulation of the parasite Toxoplasma gondii and causes it to die off inside the host cell.

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Effects of stress on adolescent brains triple networkA new studyinBiological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier, has used functional magnetic resonance imaging (fMRI) to examine the effects of acute stress and polyvicitimization, or repeated traumas, on three brain networks in adolescents.

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New knowledge about airborne virus particles could help hospitalsMeasurements taken by researchers at Lund University in Sweden of airborne virus in hospitals provide new knowledge about how best to adapt healthcare to reduce the risk of spread of infection.

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The combination makes the difference: New therapeutic approach against breast cancerResearchers at the University of Basel have now discovered an approach that involves a toxic combination with a second target gene in order to kill the abnormal cells.

Glatiramer acetate compatible with breastfeedingA study conducted by the neurology department of Ruhr-Universitt Bochum (RUB) at St. Josef Hospital on the drug glatiramer acetate can relieve mothers of this concern during the breastfeeding period.

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Taking ownership of your healthA study published this month inAge and Ageing by The Japan Collaborate Cohort (JACC) Study group at Osaka University assessed the impact of modifying lifestyle behaviors on life expectancy from middle age onwards.

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Temporomandibular Disorder-Induced Pain Likely to Worsen in Late Menopause TransitionNew study evaluates the influence of menopause symptoms on the intensity of temporomandibular disorder-induced pain throughout the full menopause transition.

Breathtaking solution for a breathless problemA drop in oxygen levels, even when temporary, can be critical to brain cells. This explains why the brain is equipped with oxygen sensors. Researchers from Japan and the United States report finding a new oxygen sensor in the mouse brain.

How calming our spinal cords could provide relief from muscle spasmsAn Edith Cowan University (ECU) studyinvestigating motoneurons in the spine has revealed two methods can make our spinal cords less excitable and could potentially be usedto treat muscle spasms.

Analysis Finds Government Websites Downplay PFAS Health RisksState and federal public health agencies often understate the scientific evidence surrounding the toxicity of per- and polyfluoroalkyl substances (PFAS) in their public communications, according toan analysispublished today in the journalEnvironmental Health.

Multiple diagnoses are the norm with mental illness; new genetic study explains whyThe study, published this weekin the journalNature Genetics, found that while there is no gene or set of genes underlying risk for all of them, subsets of disordersincluding bipolar disorder and schizophrenia; anorexia nervosa and obsessive-compulsive disorder; and major depression and anxietydo share a common genetic architecture.

Drinkers sex plus brewing method may be key to coffees link to raised cholesterolThe sex of the drinker as well as the brewing method may be key to coffees link with raised cholesterol, a known risk factor for heart disease, suggests research published in the open access journalOpen Heart.

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Other Notable Health Studies & Research From May 11, 2022 - Study Finds

Stem Cell Investig. 2019; 6: 19.

1Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;

2Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;

2Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;

3Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

1Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;

2Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;

3Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Contributions: (I) Conception and design: E Fathi, R Farahzadi; (II) Administrative support: E Fathi, R Farahzadi; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: R Farahzadi, N Rajabzadeh; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work.

Received 2018 Nov 11; Accepted 2019 Mar 17.

Recent developments in the stem cell biology provided new hopes in treatment of diseases and disorders that yet cannot be treated. Stem cells have the potential to differentiate into various cell types in the body during age. These provide new cells for the body as it grows, and replace specialized cells that are damaged. Since mesenchymal stem cells (MSCs) can be easily harvested from the adipose tissue and can also be cultured and expanded in vitro they have become a good target for tissue regeneration. These cells have been widespread used for cell transplantation in animals and also for clinical trials in humans. The purpose of this review is to provide a summary of our current knowledge regarding the important and types of isolated stem cells from different sources of animal models such as horse, pig, goat, dog, rabbit, cat, rat, mice etc. In this regard, due to the widespread use and lot of attention of MSCs, in this review, we will elaborate on use of MSCs in veterinary medicine as well as in regenerative medicine. Based on the studies in this field, MSCs found wide application in treatment of diseases, such as heart failure, wound healing, tooth regeneration etc.

Keywords: Mesenchymal stem cells (MSCs), animal model, cell-based therapy, regenerative medicine

Stem cells are one of the main cells of the human body that have ability to grow more than 200 types of body cells (1). Stem cells, as non-specialized cells, can be transformed into highly specialized cells in the body (2). In the other words, Stem cells are undifferentiated cells with self-renewal potential, differentiation into several types of cells and excessive proliferation (3). In the past, it was believed that stem cells can only differentiate into mature cells of the same organ. Today, there are many evidences to show that stem cells can differentiate into the other types of cell as well as ectoderm, mesoderm and endoderm. The numbers of stem cells are different in the tissues such as bone marrow, liver, heart, kidney, and etc. (3,4). Over the past 20 years, much attention has been paid to stem cell biology. Therefore, there was a profound increase in the understanding of its characteristics and the therapeutic potential for its application (5). Today, the utilization of these cells in experimental research and cell therapy represents in such disorders including hematological, skin regeneration and heart disease in both human and veterinary medicine (6).The history of stem cells dates back to the 1960s, when Friedenstein and colleagues isolated, cultured and differentiated to osteogenic cell lineage of bone marrow-derived cells from guinea pigs (7). This project created a new perspective on stem cell research. In the following, other researchers discovered that the bone marrow contains fibroblast-like cells with congenic potential in vitro, which were capable of forming colonies (CFU-F) (8). For over 60 years, transplantation of hematopoietic stem cells (HSCs) has been the major curative therapy for several genetic and hematological disorders (9). Almost in 1963, Till and McCulloch described a single progenitor cell type in the bone marrow which expand clonally and give rise to all lineages of hematopoietic cells. This research represented the first characterization of the HSCs (10). Also, the identification of mouse embryonic stem cells (ESCs) in 1981 revolutionized the study of developmental biology, and mice are now used extensively as one of the best option to study stem cell biology in mammals (11). Nevertheless, their application a model, have limitations in the regenerative medicine. But this model, relatively inexpensive and can be easily manipulated genetically (12). Failure to obtain a satisfactory result in the selection of many mouse models, to recapitulate particular human disease phenotypes, has forced researchers to investigate other animal species to be more probably predictive of humans (13). For this purpose, to study the genetic diseases, the pig has been currently determined as one the best option of a large animal model (14).

Stem cells, based on their differentiation ability, are classified into different cell types, including totipotent, pluripotent, multipotent, or unipotent. Also, another classification of these cells are based on the evolutionary stages, including embryonic, fetal, infant or umbilical cord blood and adult stem cells (15). shows an overview of stem cells classifications based on differentiation potency.

An overview of the stem cell classification. Totipotency: after fertilization, embryonic stem cells (ESCs) maintain the ability to form all three germ layers as well as extra-embryonic tissues or placental cells and are termed as totipotent. Pluripotency: these more specialized cells of the blastocyst stage maintain the ability to self-renew and differentiate into the three germ layers and down many lineages but do not form extra-embryonic tissues or placental cells. Multipotency: adult or somatic stem cells are undifferentiated cells found in postnatal tissues. These specialized cells are considered to be multipotent; with very limited ability to self-renew and are committed to lineage species.

Toti-potent cells have the potential for development to any type of cell found in the organism. In the other hand, the capacity of these cells to develop into the three primary germ cell layers of the embryo and into extra-embryonic tissues such as the placenta is remarkable (15).

The pluripotent stem cells are kind of stem cells with the potential for development to approximately all cell types. These cells contain ESCs and cells that are isolated from the mesoderm, endoderm and ectoderm germ layers that are organized in the beginning period of ESC differentiation (15).

The multipotent stem cells have less proliferative potential than the previous two groups and have ability to produce a variety of cells which limited to a germinal layer [such as mesenchymal stem cells (MSCs)] or just a specific cell line (such as HSCs). Adult stem cells are also often in this group. In the word, these cells have the ability to differentiate into a closely related family of cells (15).

Despite the increasing interest in totipotent and pluripotent stem cells, unipotent stem cells have not received the most attention in research. A unipotent stem cell is a cell that can create cells with only one lineage differentiation. Muscle stem cells are one of the example of this type of cell (15). The word uni is derivative from the Latin word unus meaning one. In adult tissues in comparison with other types of stem cells, these cells have the lowest differentiation potential. The unipotent stem cells could create one cell type, in the other word, these cells do not have the self-renewal property. Furthermore, despite their limited differentiation potential, these cells are still candidates for treatment of various diseases (16).

ESCs are self-renewing cells that derived from the inner cell mass of a blastocyst and give rise to all cells during human development. It is mentioned that these cells, including human embryonic cells, could be used as suitable, promising source for cell transplantation and regenerative medicine because of their unique ability to give rise to all somatic cell lineages (17). In the other words, ESCs, pluripotent cells that can differentiate to form the specialized of the various cell types of the body (18). Also, ESCs capture the imagination because they are immortal and have an almost unlimited developmental potential. Due to the ethical limitation on embryo sampling and culture, these cells are used less in research (19).

HSCs are multipotent cells that give rise to blood cells through the process of hematopoiesis (20). These cells reside in the bone marrow and replenish all adult hematopoietic lineages throughout the lifetime of the human and animal (21). Also, these cells can replenish missing or damaged components of the hematopoietic and immunologic system and can withstand freezing for many years (22).The mammalian hematopoietic system containing more than ten different mature cell types that HSCs are one of the most important members of this. The ability to self-renew and multi-potency is another specific feature of these cells (23).

Adult stem cells, as undifferentiated cells, are found in numerous tissues of the body after embryonic development. These cells multiple by cell division to regenerate damaged tissues (24). Recent studies have been shown that adult stem cells may have the ability to differentiate into cell types from various germ layers. For example, bone marrow stem cells which is derived from mesoderm, can differentiate into cell lineage derived mesoderm and endoderm such as into lung, liver, GI tract, skin, etc. (25). Another example of adult stem cells is neural stem cells (NSCs), which is derived from ectoderm and can be differentiate into another lineage such as mesoderm and endoderm (26). Therapeutic potential of adult stem cells in cell therapy and regenerative medicine has been proven (27).

For the first time in the late 1990s, CSCs were identified by John Dick in acute myeloid diseases. CSCs are cancerous cells that found within tumors or hematological cancers. Also, these cells have the characteristics of normal stem cells and can also give rise to all cell types found in a particular cancer sample (28). There is an increasing evidence supporting the CSCs hypothesis. Normal stem cells in an adult living creature are responsible for the repair and regeneration of damaged as well as aged tissues (29). Many investigations have reported that the capability of a tumor to propagate and proliferate relies on a small cellular subpopulation characterized by stem-like properties, named CSCs (30).

Embryonic connective tissue contains so-called mesenchymes, from which with very close interactions of endoderm and ectoderm all other connective and hematopoietic tissues originate, Whereas, MSCs do not differentiate into hematopoietic cell (31). In 1924, Alexander A. Maxi mow used comprehensive histological detection to identify a singular type of precursor cell within mesenchyme that develops into various types of blood cells (32). In general, MSCs are type of cells with potential of multi-lineage differentiation and self-renewal, which exist in many different kinds of tissues and organs such as adipose tissue, bone marrow, skin, peripheral blood, fallopian tube, cord blood, liver and lung et al. (4,5). Today, stem cells are used for different applications. In addition to using these cells in human therapy such as cell transplantation, cell engraftment etc. The use of stem cells in veterinary medicine has also been considered. The purpose of this review is to provide a summary of our current knowledge regarding the important and types of isolated stem cells from different sources of animal models such as horse, pig, goat, dog, rabbit, cat, rat, mice etc. In this regard, due to the widespread use and lot of attention of MSCs, in this review, we will elaborate on use of MSCs in veterinary medicine.

The isolation method, maintenance and culture condition of MSCs differs from the different tissues, these methods as well as characterization of MSCs described as (36). MSCs could be isolated from the various tissues such as adipose tissue, bone marrow, umbilical cord, amniotic fluid etc. (37).

Diagram for adipose tissue-derived mesenchymal stem cell isolation (3).

Diagram for bone marrow-derived MSCs isolation (33). MSC, mesenchymal stem cell.

Diagram for umbilical cord-derived MSCs isolation (34). MSC, mesenchymal stem cell.

Diagram for isolation of amniotic fluid stem cells (AFSCs) (35).

Diagram for MSCs characterization (35). MSC, mesenchymal stem cell.

The diversity of stem cell or MSCs sources and a wide aspect of potential applications of these cells cause to challenge for selecting an appropriate cell type for cell therapy (38). Various diseases in animals have been treated by cell-based therapy. However, there are immunity concerns regarding cell therapy using stem cells. Improving animal models and selecting suitable methods for engraftment and transplantation could help address these subjects, facilitating eventual use of stem cells in the clinic. Therefore, for this purpose, in this section of this review, we provide an overview of the current as well as previous studies for future development of animal models to facilitate the utilization of stem cells in regenerative medicine (14). Significant progress has been made in stem cells-based regenerative medicine, which enables researchers to treat those diseases which cannot be cured by conventional medicines. The unlimited self-renewal and multi-lineage differentiation potential to other types of cells causes stem cells to be frontier in regenerative medicine (24). More researches in regenerative medicine have been focused on human cells including embryonic as well as adult stem cells or maybe somatic cells. Today there are versions of embryo-derived stem cells that have been reprogrammed from adult cells under the title of pluripotent cells (39). Stem cell therapy has been developed in the last decade. Nevertheless, obstacles including unwanted side effects due to the migration of transplanted cells as well as poor cell survival have remained unresolved. In order to overcome these problems, cell therapy has been introduced using biocompatible and biodegradable biomaterials to reduce cell loss and long-term in vitro retention of stem cells.

Currently in clinical trials, these biomaterials are widely used in drug and cell-delivery systems, regenerative medicine and tissue engineering in which to prevent the long-term survival of foreign substances in the body the release of cells are controlled (40).

Today, the incidence and prevalence of heart failure in human societies is a major and increasing problem that unfortunately has a poor prognosis. For decades, MSCs have been used for cardiovascular regenerative therapy as one of the potential therapeutic agents (41). Dhein et al. [2006] found that autologous bone marrow-derived mesenchymal stem cells (BMSCs) transplantation improves cardiac function in non-ischemic cardiomyopathy in a rabbit model. In one study, Davies et al. [2010] reported that transplantation of cord blood stem cells in ovine model of heart failure, enhanced the function of heart through improvement of right ventricular mass, both systolic and diastolic right heart function (42). In another study, Nagaya et al. [2005] found that MSCs dilated cardiomyopathy (DCM), possibly by inducing angiogenesis and preventing cardial fibrosis. MSCs have a tremendous beneficial effect in cell transplantation including in differentiating cardiomyocytes, vascular endothelial cells, and providing anti-apoptotic as well angiogenic mediators (43). Roura et al. [2015] shown that umbilical cord blood mesenchymal stem cells (UCBMSCs) are envisioned as attractive therapeutic candidates against human disorders progressing with vascular deficit (44). Ammar et al., [2015] compared BMSCs with adipose tissue-derived MSCs (ADSCs). It was demonstrated that both BMSCs and ADSCs were equally effective in mitigating doxorubicin-induced cardiac dysfunction through decreasing collagen deposition and promoting angiogenesis (45).

There are many advantages of small animal models usage in cardiovascular research compared with large animal models. Small model of animals has a short life span, which allow the researchers to follow the natural history of the disease at an accelerated pace. Some advantages and disadvantages are listed in (46).

Despite of the small animal model, large animal models are suitable models for studies of human diseases. Some advantages and disadvantages of using large animal models in a study protocol planning was elaborated in (47).

Chronic wound is one of the most common problem and causes significant distress to patients (48). Among the types of tissues that stem cells derived it, dental tissuederived MSCs provide good sources of cytokines and growth factors that promote wound healing. The results of previous studies showed that stem cells derived deciduous teeth of the horse might be a novel approach for wound care and might be applied in clinical treatment of non-healing wounds (49). However, the treatment with stem cells derived deciduous teeth needs more research to understand the underlying mechanisms of effective growth factors which contribute to the wound healing processes (50). This preliminary investigation suggests that deciduous teeth-derived stem cells have the potential to promote wound healing in rabbit excisional wound models (49). In the another study, Lin et al. [2013] worked on the mouse animal model and showed that ADSCs present a potentially viable matrix for full-thickness defect wound healing (51).

Many studies have been done on dental reconstruction with MSCs. In one study, Khorsand et al. [2013] reported that dental pulp-derived stem cells (DPSCs) could promote periodontal regeneration in canine model. Also, it was shown that canine DPSCs were successfully isolated and had the rapid proliferation and multi-lineage differentiation capacity (52). Other application of dental-derived stem cells is shown in .

Diagram for application of dental stem cell in dentistry/regenerative medicine (53).

As noted above, stem cells have different therapeutic applications and self-renewal capability. These cells can also differentiate into the different cell types. There is now a great hope that stem cells can be used to treat diseases such as Alzheimer, Parkinson and other serious diseases. In stem cell-based therapy, ESCs are essentially targeted to differentiate into functional neural cells. Today, a specific category of stem cells called induced pluripotent stem (iPS) cells are being used and tested to generate functional dopamine neurons for treating Parkinson's disease of a rat animal model. In addition, NSC as well as MSCs are being used in neurodegenerative disorder therapies for Alzheimers disease, Parkinsons disease, and stroke (54). Previous studies have shown that BMSCs could reduce brain amyloid deposition and accelerate the activation of microglia in an acutely induced Alzheimers disease in mouse animal model. Lee et al. [2009] reported that BMSCs can increase the number of activated microglia, which effective therapeutic vehicle to reduce A deposits in AD patients (55). In confirmation of previous study, Liu et al. [2015] showed that transplantation of BMSCs in brain of mouse model of Alzheimers disease cause to decrease in amyloid beta deposition, increase in brain-derived neurotrophic factor (BDNF) levels and improvements in social recognition (56). In addition of BMSCs, NSCs have been proposed as tools for treating neurodegeneration disease because of their capability to create an appropriate cell types which transplanted. kerud et al. [2001] demonstrated that NSCs efficiently express high level of glial cell line-derived neurotrophic factor (GDNF) in vivo, suggesting a use of these cells in the treatment of neurodegenerative disorders, including Parkinsons disease (57). In the following, Venkataramana et al. [2010] transplanted BMSCs into the sub lateral ventricular zones of seven Parkinsons disease patients and reported encouraging results (58).

The human body is fortified with specialized cells named MSCs, which has the ability to self-renew and differentiate into various cell types including, adipocyte, osteocyte, chondrocyte, neurons etc. In addition to mentioned properties, these cells can be easily isolated, safely transplanted to injured sites and have the immune regulatory properties. Numerous in vitro and in vivo studies in animal models have successfully demonstrated the potential of MSCs for various diseases; however, the clinical outcomes are not very encouraging. Based on the studies in the field of stem cells, MSCs find wide application in treatment of diseases, such as heart failure, wound healing, tooth regeneration and etc. In addition, these cells are particularly important in the treatment of the sub-branch neurodegenerative diseases like Alzheimer and Parkinson.

The authors wish to thank staff of the Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Funding: The project described was supported by Grant Number IR.TBZMED.REC.1396.1218 from the Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Conflicts of Interest: The authors have no conflicts of interest to declare.

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Stem cell-based regenerative medicine - PMC

One is that there are some people that are naturally resistant to heart attack and have lifelong, low levels of LDL, the cardiologist says. Second, there are some genes that can be switched off that lead to very low LDL cholesterol, and individuals with those genes switched off are resistant to heart attacks.

Kathiresan and his team formed a hypothesis in 2016 that if they could develop a medicine that mimics the natural protection that some people enjoy, then they might identify a powerful new way to treat and ultimately prevent heart attacks. They launched Verve in 2018 with the goal of creating a one-time therapy that would permanently lower LDL and eliminate heart attacks caused by high LDL.

The medication is targeted specifically for patients who have a genetic form of high cholesterol known as heterozygous familial hypercholesterolemia, or FH, caused by expression of a gene called PCSK9. Verve also plans to develop a program to silence a gene called ANGPTL3 for patients with FH and possibly those with or at risk of atherosclerotic cardiovascular disease.

FH causes cholesterol to be high from birth, reaching levels of 200 to 300 milligrams per deciliter. Suggested normal levels are around 100 to 129 mg/dl, and anything above 130 mg/dl is considered high. Patients with cardiovascular disease usually are asked to aim for under 70 mg/dl, but many still have unacceptably high LDL despite taking oral medications such as statins. They are more likely to have heart attacks in their 30s, 40s and 50s, and require lifelong LDL control.

The goal for drug treatments for high LDL, Kathiresan says, is to reduce LDL as low as possible for as long as possible. Physicians and researchers also know that a sizeable portion of these patients eventually start to lose their commitment to taking their statins and other LDL-controlling medications regularly.

If you ask 100 patients one year after their heart attack what fraction are still taking their cholesterol-lowering medications, its less than half, says Kathiresan. So imagine a future where somebody gets a one-time treatment at the time of their heart attack or before as a preventive measure. Its right in front of us, and its something that Verve is looking to do.

In late 2020, Verve completed primate testing with monkeys that had genetically high cholesterol, using a one-time intravenous injection of VERVE-101. It reduced the monkeys LDL by 60 percent and, 18 months later, remains at that level. Kathiresan expects the LDL to stay low for the rest of their lives.

Verves gene editing medication is packaged in a lipid nanoparticle to serve as the delivery mechanism into the liver when infused intravenously. The drug is absorbed and makes its way into the nucleus of the liver cells.

Verves program targeting PCSK9 uses precise, single base, pair base editing, Kathiresan says, meaning it doesn't cut DNA like CRISPR gene editing systems do. Instead, it changes one base, or letter, in the genome to a different one without affecting the letters around it. Comparing it to a pencil and eraser, he explains that the medication erases out a letter A and makes it a letter G in the A, C, G and T code in DNA.

By making that simple change from A to G, the medication switches off the PCSK9 gene, automatically lowering LDL cholesterol.

Once the DNA change is made, all the cells in the liver will have that single A to G change made, Kathiresan says. Then the liver cells divide and give rise to future liver cells, but every time the cell divides that change, the new G is carried forward.

Additionally, Verve is pursuing its second gene editing program to eliminate ANGPTL3, a gene that raises both LDL and blood triglycerides. In 2010, Kathiresan's research team learned that people who had that gene completely switched off had LDL and triglyceride levels of about 20 and were very healthy with no heart attacks. The goal of Verves medication will be to switch off that gene, too, as an option for additional LDL or triglyceride lowering.

Success with our first drug, VERVE-101, will give us more confidence to move forward with our second drug, Kathiresan says. And it opens up this general idea of making [genomic] spelling changes in the liver to treat other diseases.

The approach is less ethically concerning than other gene editing technologies because it applies somatic editing that affects only the individual patient, whereas germline editing in the patients sperm or egg, or in an embryo, gets passed on to children. Additionally, gene editing therapies receive the same comprehensive amount of testing for side effects as any other medicine.

We need to continue to advance our approach and tools to make sure that we have the absolute maximum ability to detect off-target effects, says Euan Ashley, professor of medicine and genetics at Stanford University and founding director of its Center for Inherited Cardiovascular Disease. Ashley and his colleagues at Stanfords Clinical Genomics Program and beyond are increasingly excited about the promise of gene editing.

We can offer precision diagnostics, so increasingly were able to define the disease at a much deeper level using molecular tools and sequencing, he continues. We also have this immense power of reading the genome, but were really on the verge of taking advantage of the power that we now have to potentially correct some of the variants that we find on a genome that contribute to disease.

He adds that while the gene editing medicines in development to correct genomes are ahead of the delivery mechanisms needed to get them into the body, particularly the heart and brain, hes optimistic that those arent too far behind.

It will probably take a few more years before those next generation tools start to get into clinical trials, says Ashley, whose book, The Genome Odyssey, was published last year. The medications might be the sexier part of the research, but if you cant get it into the right place at the right time in the right dose and not get it to the places you dont want it to go, then that tool is not of much use.

Medical experts consider knocking out the PCSK9 gene in patients with the fairly common genetic disorder of familial hypercholesterolemia roughly one in 250 people a potentially safe approach to gene editing and an effective means of significantly lowering their LDL cholesterol.

Nurse Erin McGlennon has an Implantable Cardioverter Defibrillator and takes medications, but she is also hopeful that a gene editing medication will be developed in the near future.

Erin McGlennon

Mary McGowan, MD, chief medical officer for The Family Heart Foundation in Pasadena, CA, sees the tremendous potential for VERVE-101 and believes patients should be encouraged by the fact that this kind of research is occurring and how much Verve has accomplished in a relatively short time. However, she offers one caveat, since even a 60 percent reduction in LDL wont completely eliminate the need to reduce the remaining amount of LDL.

This technology is very exciting, she said, but we want to stress to our patients with familial hypercholesterolemia that we know from our published research that most people require several therapies to get their LDL down., whether that be in primary prevention less than 100 mg/dl or secondary prevention less than 70 mg/dl, So Verves medication would be an add-on therapy for most patients.

Dr. Kathiresan concurs: We expect our medicine to lower LDL cholesterol by about 60 percent and that our patients will be on background oral medications, including statins that lower LDL cholesterol.

Several leading research centers are investigating gene editing treatments for other types of cardiovascular diseases. Elizabeth McNally, Elizabeth Ward Professor and Director at the Center for Genetic Medicine at Northwestern Universitys Feinberg School of Medicine, pursues advanced genetic correction in neuromuscular diseases such as Duchenne muscular dystrophy and spinal muscular atrophy. A cardiologist, she and her colleagues know these diseases frequently have cardiac complications.

Even though the field is driven by neuromuscular specialists, its the first therapies in patients with neuromuscular diseases that are also expected to make genetic corrections in the heart, she says. Its almost like an afterthought that were potentially fixing the heart, too.

Another limitation McGowan sees is that too many healthcare providers are not yet familiar with how to test patients to determine whether or not they carry genetic mutations that need to be corrected. We need to get more genetic testing done, she says. For example, thats the case with hypertrophic cardiomyopathy, where a lot of the people who probably carry that diagnosis and have never been genetically identified at a time when genetic testing has never been easier.

One patient who has been diagnosed with hypertrophic cardiomyopathy also happens to be a nurse working in research at Genentech Pharmaceutical, now a member of the Roche Group, in South San Francisco. To treat the disease, Erin McGlennon, RN, has an Implantable Cardioverter Defibrillator and takes medications, but she is also hopeful that a gene editing medication will be developed in the near future.

With my condition, the septum muscles are just growing thicker, so Im on medicine to keep my heart from having dangerous rhythms, says McGlennon of the disease that carries a low risk of sudden cardiac death. So, the possibility of having a treatment option that can significantly improve my day-to-day functioning would be a major breakthrough.

McGlennon has some control over cardiovascular destiny through at least one currently available technology: in vitro fertilization. Shes going through it to ensure that her children won't express the gene for hypertrophic cardiomyopathy.

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