Tissue-specific stem cells

Tissue-specific stem cells, which are sometimes referred to as adult or somatic stem cells, are already somewhat specialized and can produce some or all of the mature cell types found within the particular tissue or organ in which they reside. Because of their ability to generate multiple, organ-specific, cell types, they are described as multipotent. For example, stem cells found

Stem cells are the foundation cells for every organ and tissue in our bodies. The highly specialized cells that make up these tissues originally came from an initial pool of stem cells formed shortly after fertilization. Throughout our lives, we continue to rely on stem cells to replace injured tissues and cells that are lost every day, such as those in our skin, hair, blood and the lining of our gut. Stem cells have two key properties: 1) the ability to self-renew, dividing in a way that makes copies of themselves, and 2) the ability to differentiate, giving rise to the mature types of cells that make up our organs and tissues.

Tissue-specific stem cells Tissue-specific stem cells, which are sometimes referred to as adult or somatic stem cells, are already somewhat specialized and can produce some or all of the mature cell types found within the particular tissue or organ in which they reside. Because of their ability to generate multiple, organ-specific, cell types, they are described as multipotent. For example, stem cells found within the adult brain are capable of making neurons and two types of glial cells, astrocytes and oligodendrocytes. Tissue-specific stem cells have been found in several organs that need to continuously replenish themselves, such as the blood, skin and gut and have even been found in other, less regenerative, organs such as the brain. These types of stem cells represent a very small population and are often buried deep within a given tissue, making them difficult to identify, isolate and grow in a laboratory setting. Neuron Dr. Gerry Shaw, EnCor Biotechnology Inc. Astrocyte Abcam Inc. Oligodendrocyte Dhaunchak and Nave (2007). Proc Natl Acad Sci USA 104:17813-8 http://www.isscr.org Embryonic stem cells Embryonic stem cells have been derived from a variety of species, including humans, and are described as pluripotent, meaning that they can generate all the different types of cells in the body. Embryonic stem cells can be obtained from the blastocyst, a very early stage of development that consists of a mostly hollow ball of approximately 150-200 cells and is barely visible to the naked eye. At this stage, there are no organs, not even blood, just an inner cell mass from which embryonic stem cells can be obtained. Human embryonic stem cells are derived primarily from blastocysts that were created by in vitro fertilization (IVF) for assisted reproduction but were no longer needed. The fertilized egg and the cells that immediately arise in the first few divisions are totipotent. This means that, under the right conditions, they can generate a viable embryo (including support tissues such as the placenta). Within a matter of days, however, these cells transition to become pluripotent. None of the currently studied embryonic stem cell lines are alone capable of generating a viable embryo (i.e., they are pluripotent, not totipotent). Why are embryonic stem cells so valuable? Unlike tissue-specific (adult) stem cells, embryonic stem cells have the potential to generate every cell type found in the body. Just as importantly, these cells can, under the right conditions, be grown and expanded indefinitely in this unspecialized or undifferentiated state. These cells help researchers learn about early human developmental processes that are otherwise inaccessible, study diseases and establish strategies that could ultimately lead to therapies designed to replace or restore damaged tissues. Induced pluripotent stem cells One of the hottest topics in stem cell research today is the study of induced pluripotent stem cells (iPS cells). These are adult cells (e.g., skin cells) that are engineered, or reprogrammed, to become pluripotent, i.e., behave like an embryonic stem cell. While these iPS cells share many of the same characteristics of embryonic stem cells, including the ability to give rise to all the cell types in the body, it is important to understand that they are not identical. The original iPS cells were produced by using viruses to insert extra copies of three to four genes known to be important in embryonic stem cells into the specialized cell. It is not yet completely understood how these three to four reprogramming genes are able to induce pluripotency; this question is the focus of ongoing research. In addition, recent studies have focused on alternative ways of reprogramming cells using methods that are safer for use in clinical settings. Disease- or patient-specific pluripotent stem cells One of the major advantages of iPS cells, and one of the reasons that researchers are very interested in studying them, is that they are a very good way to make pluripotent stem cell lines that are specific to a disease or even to an individual patient. Disease-specific stem cells are powerful tools for studying the cause of a particular disease and then for testing drugs or discovering other approaches to treat or cure that disease. The development of patientspecific stem cells is also very attractive for cell therapy, as these cell lines are from the patient themselves and may minimize some of the serious complications of rejection and immunosuppression that can occur following transplants from unrelated donors. Moving stem cells into the clinic Clinical translation is the process used to turn scientific knowledge into real world medical treatments. Researchers take what they have learned about how a tissue usually works and what goes wrong in a particular disease or injury and use this information to develop new ways to diagnose, stop or fix what goes wrong. Before being marketed or adopted as standard of care, most treatments are tested through clinical trials. Sometimes, in attempting new surgical techniques or where the disease or condition is rare and does not have a large enough group of people to form a clinical trial, certain treatments might be tried on one or two people, a form of testing sometimes referred to as innovative medicine. For more information on how science becomes medicine, please visit http://www.closerlookatstemcells.org. Current therapies Blood stem cells are currently the most frequently used stem cells for therapy. For more than 50 years, doctors have been using bone marrow transplants to transfer blood stem cells to patients, and more advanced techniques for collecting blood stem cells are now being used to treat leukemia, lymphoma and several inherited blood disorders. Umbilical cord blood, like bone marrow, is often collected as a source of blood stem cells and in certain cases is being used as an alternative to bone marrow transplantation. Additionally, some bone, skin and corneal diseases or injuries can be treated by grafting tissues that are derived from or maintained by stem cells. These therapies have also been shown to be safe and effective. Potential therapies Other stem cell treatments, while promising, are still at very early experimental stages. For example, the mesenchymal stem cell, found throughout the body including in the bone marrow, can be directed to become bone, cartilage, fat and possibly even muscle. In certain experimental models, these cells also have some ability to modify immune functions. These abilities have created considerable interest in developing ways of using mesenchymal stem cells to treat a range of musculoskeletal abnormalities, cardiac disease and some immune abnormalities such as graft-versus-host disease following bone marrow transplant. Remaining challenges Despite the successes we have seen so far, there are several major challenges that must be addressed before stem cells can be used as cell therapies to treat a wider range of diseases. First, we need to identify an abundant source of stem cells. Identifying, isolating and growing the right kind of stem cell, particularly in the case of rare adult stem cells, are painstaking and difficult processes. Pluripotent stem cells, such as embryonic stem cells, can be grown indefinitely in the lab and have the advantage of having the potential to become any cell in the body, but these processes are again very complex and must be tightly controlled. iPS cells, while promising, are also limited by these concerns. In both cases, considerable work remains to be done to ensure that these cells can be isolated and used safely and routinely. Second, as with organ transplants, it is very important to have a close match between the donor tissue and the recipient; the more closely the tissue matches the recipient, the lower the risk of rejection. Being able to avoid the lifelong use of immunosuppressants would also be preferable. The discovery of iPS cells has opened the door to developing patient-specific pluripotent stem cell lines that can later be developed into a needed cell type without the problems of rejection and immunosuppression that occur from transplants from unrelated donors. Third, a system for delivering the cells to the right part of the body must be developed. Once in the right location, the new cells must then be encouraged to integrate and function together with the bodys other cells. http://www.isscr.org Glossary Blastocyst A very early embryo that has the shape of a ball and consists of approximately 150-200 cells. It contains the inner cell mass, from which embryonic stem cells are derived, and an outer layer of cells called the trophoblast that forms the placenta. Cell line Cells that can be maintained and grown in a dish outside of the body. Clinical translation The process of using scientific knowledge to design, develop and apply new ways to diagnose, stop or fix what goes wrong in a particular disease or injury. Differentiation The process of development with an increase in the level of organization or complexity of a cell or tissue, accompanied by a more specialized function. Embryo The early developing organism; this term denotes the period of development between the fertilized egg and the fetal stage. Embryonic stem cell Cells derived from very early in development, usually the inner cell mass of a developing blastocyst. These cells are self-renewing (can replicate themselves) and pluripotent (can form all cell types found in the body). Induced pluripotent stem (iPS) cell Induced pluripotent cells (iPS cells) are stem cells that were engineered (induced) from non-pluripotent cells to become pluripotent. In other words, a cell with a specialized function (for example, a skin cell) that has been reprogrammed to an unspecialized state similar to that of an embryonic stem cell. Innovative medicine Treatments that are performed on a small number of people and are designed to test a novel technique or treat a rare disease. These are done outside of a typical clinical trial framework. In vitro fertilization A procedure in which an egg cell and sperm cells are brought together in a dish to fertilize the egg. The fertilized egg will start dividing and, after several divisions, forms the embryo that can be implanted into the womb of a woman and give rise to pregnancy. Mesenchymal stem cells Mesenchymal stem cells were originally discovered in the bone marrow, but have since been found throughout the body and can give rise to a large number of connective tissue types such as bone, cartilage and fat. Multipotent stem cells Stem cells that can give rise to several different types of specialized cells, but in contrast to a pluripotent stem cell, are restricted to a certain organ or tissue types. For example, blood stem cells are multipotent cells that can produce all the different cell types that make up the blood but not the cells of other organs such as the liver or brain. Pluripotent stem cells Stem cells that can become all the cell types that are found in an implanted embryo, fetus or developed organism. Embryonic stem cells are pluripotent stem cells. Self-renewal The process by which a cell divides to generate another cell that has the same potential. Stem cells Cells that have both the capacity to self-renew (make more stem cells by cell division) and to differentiate into mature, specialized cells. Tissue-specific stem cells (also known as adult or somatic stem cells) Stem cells found in different tissues of the body that can give rise to some or all of the mature cell types found within the particular tissue or organ from which they came, i.e., blood stem cells can give rise to all the cells that make up the blood, but not the cells of organs such as the liver or brain. Totipotent stem cells Stem cells that, under the right conditions, are wholly capable of generating a viable embryo (including the placenta) and, for humans, exist until about four days after fertilization, prior to the blastocyst stage from which embryonic stem cells are derived.

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What Are Stem Cells - Checkbiotech.org (press release)

IPS Cell Therapy Comments Off on What Are Stem Cells – Checkbiotech.org (press release) | June 4th, 2017

Seven drugs of the current top-10 best selling drugs are biologics, the penetration of biologic drugs is expected to reach 30% by 2020 of the global pharmaceutical market and some of the key modalities include monoclonal antibodies, recombinant proteins, peptides, cell and gene therapy products.

Dr Subir Basak Chief Business Officer, GVK Biosciences

Over the last two decades, the Pharmaceutical industry has seen a radical change. The unprecedented downsizing of the internal discovery of big pharmaceuticals, patent expiration, shift towards biologics have seen a surge in the externalization and outsourcing activities. As the industry is looking for new sources of discovery and innovation with limited resources, there is a growing preference to move towards externalization and willingness to embrace the concept of outsourcing.

Seven drugs of the current top- 10 best selling drugs are biologics, the penetration of biologic drugs is expected to reach 30% by 2020 of the global pharmaceutical market and some of the key modalities include monoclonal antibodies, recombinant proteins, peptides, cell and gene therapy products. Global R&D spend in the biopharmaceutical industry is estimated to be $194 billion in 2016 and according to industry experts, 75-80% of the expenses can be outsourced. However, current penetration rate is around 58% which presents a huge opportunity for the CROs to tap the Trends in Drug Discovery Outsourcing: A Perspective market. The global pharmaceutical outsourcing market was estimated to be $113.7 billion in 2016 and out of which 49% is accounted for CROs. Among the $55.7 billion CRO market, 31.2% accounts for discovery-based service i.e. $17.4 billion in 2016 and the remaining 68.8% accounts for Preclinical and clinical services.

Biology related services segment is a high growth area with huge potential and expected to grow faster at a CAGR of 17.2% compared to the small molecules segment due to increase in budget allocations for R&D by biopharmaceutical companies.

The drug discovery CRO industry is witnessing increased consolidation. Many Asia-based companies are increasing their foothold in Europe and North America. GVK BIO, a Contract Research & Development Organization (CRDO) from India has taken over Aragen Bioscience. Aragen has early stage discovery biologics capabilities and played a leading role in oncology and fibrosis based animal models for preclinical biotechs in bay area. Similarly, ChemPartner established research facility in South San Francisco. Also, WuXi AppTec acquired HD Biosciences (HDB), a biology focused preclinical drug discovery CRO.

Advancement in drug discovery technologies such as iPS cells, automated high content screening, patch clamp, gene editing and DNAencoded libraries have expedited the drug discovery process with increased efficiency. There is an increased interest in the use of DNAencoded libraries (small molecules tagged with DNAs) by major pharma companies.Majority of the companies offering DNA-encoded library services are from US (DiCE, X-Chem, Ensemble therapeutics) and Europe (Nuevolution, Vipergen, Cominnex, Philochem). Thereseems to be very little competition in APAC. This trend should push some of the CROs from APAC region to acquire companies with proprietary technology in DNA-encoded libraries or to build capabilities and this seems likely to be a focus point for majority of the CROs especially from APAC.

Evolving business models including risk-based and insourcing are facilitating better collaboration between pharmaceutical companies and CROs. Some of the companies established a new business model known as insourcing which is a new sourcing for pharma where CROs work on-site at customer location in an integrated fashion. This new model provides outstanding performance with efficient cost and time.

CROs should build capabilities to differentiate in the area of Target Identification/Target Validation on how to use human disease pathology knowledge/primary tissues from humans clubbed with Omics knowledge to further validate the concepts. As most of the CROs propose targets from literature and sponsor companies consider it as risky option to invest in such projects without substantial evidences. As a de-risking strategy some CROs are investing internally and validating the concept by siRNA, knockdown approaches and take the concept to a level-up and then approach the sponsors companies who are working in similar area. This approach would increase the sponsor confidence in the CRO program.

There is a huge demand for the novel therapeutics addressing the unmet needs, for example, there are no FDA approved drugs or any therapies for NASH treatment and there is a tremendous opportunity for CROs to work on novel targets, preclinical models and biomarker to come-up with some early stage assets for partnering. Owing to market attractiveness, there is funding provided by venture capitalists to promising players, while some investors are even launching new companies to specifically work on NASH projects. For instance in February 2017, Versant Ventures formed Jecure Therapeutics through $20 million investment for NASH program development. Similarly, Third Rock Ventures formed Pliant Therapeutics with $45 million investment for TGF- signaling based NASH treatment. These companies could potentially outsource majority of the work to CROs in APAC region.

Asia is emerging as a preferred destination for outsourcing drug discovery activities due to the vast availability of skilled manpower, lower costs, favorable regulatory environment and quality data. In addition the local governments are focusing on development of healthcare and pharmaceutical industryby ensuring focus on high quality & compliance in terms of higher regulatory surveillance and training programs. Japan being the second largest pharmaceutical market in the world provides huge opportunity for CROs from APAC. Chinese and Indian pharmaceutical markets are one of the fastest growing in the world and are considered to be the preferred locations for drug discovery outsourcing primarily because of the end-to-end technological capabilities developed over several years. Asian CROs have strong capabilities in biologics research services and built new technology platforms for high-throughput screening, genomics and proteomics research panel screening, enzymatic, and binding assays. They are also well equipped with transgenic and disease animal models that have been developed for target validation, efficacy, and safety studies, thereby providing clients with end-to-end services. Indian CROs typically focus more on new chemical entities and offer integrated discovery services at much lower cost.

Therapeutic area gap analysis research indicates that the key contract research organizations in Asia pacific region are majorly focusing on Oncology, metabolic diseases, Inflammation and CNS. However, majority of Pharma companies in addition to the above therapeutic areas are also focusing on other areas like cardiovascular, immunology, infectious diseases. Since there is a high gap in these therapeutic areas, the CROs should increase their focus in order to tap the opportunity.

Growth in biologics research and orphan drugs, innovative technological platforms and evolving business models encourage pharma and biotech companies to outsource. Even though, big pharma is moving towards research institutions and academia to accelerate knowledge and leverage innovation and technology platforms, they lack the infrastructure to move the drugs from early stages of drug discovery. These factors are expected to enhance drug discovery outsourcing market in APAC region for the coming years.

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Trends in Drug Discovery Outsourcing: A Perspective - BSA bureau (press release)

IPS Cell Therapy Comments Off on Trends in Drug Discovery Outsourcing: A Perspective – BSA bureau (press release) | June 2nd, 2017

BENGALURU:Full-fledged treatment for cancer and bone-related ailments using stem-cell within the state could soon be a possibility if a plan of a world renowned surgeon from the state succeeds.

Dr A A Shetty is a highly decorated orthopedic surgeon and professor based in the UK who won the Nobel equivalent of surgery called the Hunterian Medal, this year. In his aim to bring about next level cancer and orthopedic treatment, he has already set up two big stem cell research labs - one in Dharwad and another in Mangaluru, a few years back at a cost of around 20 to 25 crore. A hospital that will treat stem-related ailments has also been envisaged at a total cost of around Rs 200 to 250 crore.

Setting up the labs is part of a three-step goal. After setting up the labs, the next step will be producing the stem cells, whether it be for bone ailments, treatment for cervical cancer etc. Then the third step will be the application of these stem cells through our hospital or through tie-ups with other hospitals. I have already received the funding for setting up the hospital, says Dr Shetty in an interaction with CE in Bengaluru. He is originally from a small village called Asode in Udupi district.

The lab in Dharwad is located at SDM College and is being backed by Shri Dharmasthala Manjunatheshwara and will be primarily working on blood cancer and thalassemia treatment. The one in Mangaluru is located at K.S. Hegde Medical Academy (KSHEMA) and is backed by the NITTE group. It will work on cartilage and bone fracture treatments.The effort is no doubt for profit. We will charge the rich but the poor will be treated for free at our hospital, he says.

Already, Shetty has recruited a number of top stem cell researchers from the state who are presently abroad. I have recruited researchers who were doing their postdoc studies in Japan, South Korea. Presently there are four of them working at the two labs, he says. Shetty ultimately wants to settle in Karnataka and hopes to achieve his goal by 2020. The third stage of his plan also requires expertise in various cutting edge technologies such as robotics, computing and he will also be recruiting people who specialize in these fields.

Cancer Vaccination

Shetty also hopes to make cancer vaccination a possibility. Giving an example of cervical cancer, Shetty says, Few cancers can be vaccinated. Cervical cancer, one of the most rampant cancers, is one of them. We will use stems derived from iPS cell. In the UK, the vaccine cost 60 pounds. Our aim is to develop it and sell it at a very low cost, as low as Rs 100, he adds. Induced Pluripotent Stem Cells or iPS Cells are derived from the blood and skiwwn cells and can be reprogrammed to provide an unlimited source of any type of human cell.

Stem cells for Arthritis In 2013, Shetty devised a minimally invasive procedure to treat arthritis using stem cells. When the cartilage between the bones begin to erode, the bones rub against each other and cause severe pain. Shetty treated a patient suffering from knee arthritis. He drilled a hole into the patients knee bone and released stem cells that could grow into the cartilage. In all, the procedure lasted just 30 minutes. Shetty has already done as many as two dozen such procedures in India.

Trauma Center Shetty also says that he wants to develop and provide integrated trauma services. If a patient survives the golden hour then he/she can be saved. Majority die in the first hour of trauma. My integrated services will have specialized suits that will help reduce blood loss and will have other know-how. I am negotiating with the International Rotary on this, he adds. This may be established either in Mangalore or Bangalore.

Dr Vishal Rao, head and neck oncology surgeon at HCG Hospitals says that stem cells research is in the mid-stage of development and has great potential to grow in India. The IT and BT ministry is already taking great steps by encouraging startups on these lines, starting various schemes, he says. Vishal also pointed out that a number of private organizations, hospitals and individuals like those like Dr Shetty are also investing in the field.

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Stem-cell therapy for cancer comes closer home - The New Indian Express

IPS Cell Therapy Comments Off on Stem-cell therapy for cancer comes closer home – The New Indian Express | May 23rd, 2017

News

Published online 22 May 2017

Two teams of Arab and American researchers are tantalizingly close to generating primordial blood stem cells in the lab.

Louise Sarant

Hematopoietic stem and progenitor cells (HSPC) from human iPS cells. Rio Sugimura Two teams of scientists have developed methods that make lab-grown blood stem cells a realistic prospect a goal for hematology researchers since human embryonic stem (ES) cells were first isolated in 1998.

Scientists have previously succeeded in genetically reprogramming skin cells to make pluripotent stem (iPS) cells, which are later used to generate multiple human cell types. However, the ability to induce blood stem cells that self-regenerate, for the treatment of millions affected by blood cancers and genetic disorders, has eluded researchers.

The two papers newly published in Nature describe methods that pave the way for safe, artificial and bona fide hematopoietic stem cells (HSCs) generation. Hematopoietic stem (HSC) cells are the common ancestor of all cells created in the body, producing billions of blood cells every day.

This bears major implications for cell therapy, drug screening and leukemia research. The root causes of blood diseases can be scrutinized and creating immune-matched blood cells, derived from a patients own cells, is now conceivable.

The first team, based at the Boston Childrens Hospital, has generated blood-forming stem cells (HSCs) in the lab using pluripotent stem cells for the first time.

Were tantalizingly close to generating bona fide human blood stem cells in a dish, says senior investigator George Daley, who heads the research lab in Boston Childrens Hospitals stem cell program and who is dean of Harvard Medical School. This work is the culmination of over 20 years of striving.

Ryohichi Rio Sugimura, the studys first author and a postdoctoral fellow in the Daley Lab, says his team exposed human pluripotent stem cells (both ES and iPS cells) to chemical signals to prompt them to differentiate into specialized cells and tissues during embryonic development.

"Sugimura and his colleagues delivered transcription factors proteins that control and regulate the transcription of specific genes into the cells using a lentivirus, a vector to deliver genes. The resultant cells were transplanted to immune deficient mice, where human blood and immune cells were made, he says.

A few weeks after the transplant, a small number of rodents were found to be carrying multiple types of blood cells in their bone marrow and blood; cells that are also found in human blood. This is a major step forward for our ability to investigate genetic blood disease, says Daley.

The second team, a group of scientists from Weill Cornell Qatar and Weill Cornell Medicine in New York, used mature mouse endothelial cells cells that line blood vessels as their starting material for generating HSCs.

Image of human CD45+ blood cells differentiated from iPS cells. Rio Sugimura Based on previous work, we hypothesized that endothelial cells are the mastermind of organ development, explains Jeremie Arash Rafii Tabrizi, paper co-author and researcher at the stem cell and microenvironment laboratory at Weill Cornell Medicine, Qatar.

The team isolated the cells, and then pushed key transcription factors into their genomes. Between days 8 and 20 into the process, the cells specified and multiplied.

Our research showed that endothelial cells can be converted into competent HSCs with the ability to both regenerate the myeloid and lymphoid lineage, he explains.

The method brings hope for people afflicted with leukemia requiring HSCs transplantation, or genetic disorders affecting the myeloid or lymphoid lineages. The clinical generation of HSCs, derived from the same individual, can eventually help scientists correct genetic abnormalities.

As exciting as the two studies are, rigorous tests are still required to check the normality of lab-grown cells before the clinical phase, says Alexander Medvinsky, professor of hematopoietic stem cell biology at the University of Edinburgh Medical Research Council Centre for Regenerative Medicine. Medvinsky was not involved in either study.

The risks of infusion of genetically engineered cells in humans should not be underestimated, he weighs in. Tests and trials to generate safe fully functional human blood stem cells may take many years, in contrast to similar assessment in short-living mice. It is not clear now whether blood stem cells can become cancerous in the longer term.

He adds however that this type of research is exactly what is required to potentially meet clinical needs.

doi:10.1038/nmiddleeast.2017.89

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Lab-grown blood stem cells - Nature Middle East

IPS Cell Therapy Comments Off on Lab-grown blood stem cells – Nature Middle East | May 22nd, 2017

Inquirer.net

Approaching a decades-old goal: Making blood stem cells from patients' own cells Science Daily ... lab using pluripotent stem cells, which can make virtually every cell type in the body. The advance opens new avenues for research into the root causes of blood diseases and to creating immune-matched blood cells for treatment purposes, derived ... 'Milestone' in quest to make blood cells studiesInquirer.net all 21 news articles »

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Approaching a decades-old goal: Making blood stem cells from patients' own cells - Science Daily

IPS Cell Therapy Comments Off on Approaching a decades-old goal: Making blood stem cells from patients’ own cells – Science Daily | May 18th, 2017

2016.09.20 MEDIAAlvetex wins CV Technology Innovator Awards 2016

ReproCELL is proud to announce its groundbreaking 3D cell culture technology Alvetex has been awarded the Corporate Vision Technology Innovator Award 2016. Read the full interview with Prof. Dr. Stefan Przyborski, ReproCELL Europes Chief Scientific Officer and inventor of Alvetex, here: http://reinnervate.com/reprocell-europe-wins-cv-tech-innovator-awards-2016-alvetex/

We will exhibit and presentat a poster at ISSCR 2016 Annual Meeting, San Francisco, USA. We will like to welcome you to stop by our booth and posters. ISSCR 2016 Annual Meeting URL http://www.isscr.org/home/annual-meeting/san-francisco-2016 Date JUNE 22-25, 2016 Place San Francisco, America Booth: Date JUNE 22-25, 2016 Booth No. 1608 POSTER Date & Time JUNE 22, 2016630PM730PM Poster No. Poster W1093 Title Improvement of human iPS cell-derived hepatocyte functionality using 3D culture systems Presenter ReproCELL, Inc. Zachary Yu Ching Lin Date & Time JUNE 22, 2016730PM830PM Poster No. Poster W2064 Title Non-modified RNAs for the derivation of clinically relevant iPS cell lines from adult []

We make the presentation a poster at 11th International ISSX Meeting at Busan, Korea. Please stop by at our poster if you attend to the meeting. 11th International ISSX Meeting URL http://issxbusan2016.org/ Date June 12-16, 2016 Place Busan, Korea POSTER Date June 15, 201612151300Poster session 2 Location Exhibit Hall (Grand Ballroom 3F) Poster No. P52 Title Stabilized and Enhanced CYP450 Enzyme Activity in Cultured Human Primary Hepatocytes is Conferred by ReproHP Medium Host Sales & Marketing DepartmentPaul CIZDZIEL Wirtz Julia POSTER Date June 15, 201612151300Poster session 2 Location Exhibit Hall (Grand Ballroom 3F) Poster No. P232 Title Improving the prediction of oral bioavailability using fresh []

Webinar: iPSC derived Cells & hiPSC/ES media June 4th 2013 10 AM CEST Please register from here; https://attendee.gotowebinar.com/register/7334590631056470272

ReproCELLs iPS cell technology featured in NHK World news http://www3.nhk.or.jp/nhkworld/english/movie/feature201303211118.html

An article written jointly by Kyoto University and ReproCELL was published in Cell Rep. 2012 Nov 29;2(5):1448-60.. Small Molecule that Promotes Cardiac Differentiation of Human Pluripotent Stem Cells under Defined, Cytokine- and Xeno-free Conditions

ReproCELLs iPS cell business was widely introduced in Japanese TV news on Prof. Shinya Yamanakas Nobel Prize.

ReproCELLs iPS cell-derived cardiomyocytes, neurons and hepatocytes were introduced in Genetic Engineering & Biotechnology News (GEN). Jan 15, 2012 (Vol. 32, No. 2) Stem Cell Applications Hasten into the Clinic

An article in Genetic Engineering & Biotechnology News, Pharmas R&D Focus Shifting to Stem Cells -Investors Interest in These Cells Increases as Scientists Continue to Unleash Their Potential introduces ReproCELLs new cardiotoxicity assay using iPSCs, QTempo, as well as its neural stem cell research. Read the article

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ReproCELL - Stem Cell Innovation

IPS Cell Therapy Comments Off on ReproCELL – Stem Cell Innovation | May 14th, 2017

Cell potency is a cell's ability to differentiate into other cell types.[1][2] The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell which like a continuum begins with totipotency to designate a cell with the most differentiation potential, pluripotency, multipotency, oligopotency and finally unipotency. Potency is taken from the Latin term "potens" which means "having power".

Totipotency is the ability of a single cell to divide and produce all of the differentiated cells in an organism. Spores and zygotes are examples of totipotent cells.[3] In the spectrum of cell potency, totipotency represents the cell with the greatest differentiation potential. Toti comes from the Latin totus which means "entirely".

It is possible for a fully differentiated cell to return to a state of totipotency.[4] This conversion to totipotency is complex, not fully understood and the subject of recent research. Research in 2011 has shown that cells may differentiate not into a fully totipotent cell, but instead into a "complex cellular variation" of totipotency.[5] Stem cells resembling totipotent blastomeres from 2-cell stage embryos can arise spontaneously in the embryonic stem cell cultures[6][7] and also can be induced to arise more frequently in vitro through down-regulation of the chromatin assembly activity of CAF-1.[8]

The human development model is one which can be used to describe how totipotent cells arise.[9] Human development begins when a sperm fertilizes an egg and the resulting fertilized egg creates a single totipotent cell, a zygote.[10] In the first hours after fertilization, this zygote divides into identical totipotent cells, which can later develop into any of the three germ layers of a human (endoderm, mesoderm, or ectoderm), into cells of the cytotrophoblast layer or syncytiotrophoblast layer of the placenta. After reaching a 16-cell stage, the totipotent cells of the morula differentiate into cells that will eventually become either the blastocyst's Inner cell mass or the outer trophoblasts. Approximately four days after fertilization and after several cycles of cell division, these totipotent cells begin to specialize. The inner cell mass, the source of embryonic stem cells, becomes pluripotent.

Research on Caenorhabditis elegans suggests that multiple mechanisms including RNA regulation may play a role in maintaining totipotency at different stages of development in some species.[11] Work with zebrafish and mammals suggest a further interplay between miRNA and RNA binding proteins (RBPs) in determining development differences.[12]

In September 2013, a team from the Spanish national Cancer Research Centre was able for the first time to make adult cells from mice retreat to the characteristics of embryonic stem cells, thereby achieving totipotency.[13]

In cell biology, pluripotency (from the Latin plurimus, meaning very many, and potens, meaning having power)[14] refers to a stem cell that has the potential to differentiate into any of the three germ layers: endoderm (interior stomach lining, gastrointestinal tract, the lungs), mesoderm (muscle, bone, blood, urogenital), or ectoderm (epidermal tissues and nervous system).[15] However, cell pluripotency is a continuum, ranging from the completely pluripotent cell that can form every cell of the embryo proper, e.g., embryonic stem cells and iPSCs (see below), to the incompletely or partially pluripotent cell that can form cells of all three germ layers but that may not exhibit all the characteristics of completely pluripotent cells.

Induced pluripotent stem cells, commonly abbreviated as iPS cells or iPSCs are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a "forced" expression of certain genes and transcription factors.[16] These transcription factors play a key role in determining the state of these cells and also highlights the fact that these somatic cells do preserve the same genetic information as early embryonic cells.[17] The ability to induce cells into a pluripotent state was initially pioneered in 2006 using mouse fibroblasts and four transcription factors, Oct4, Sox2, Klf4 and c-Myc;[18] this technique, called reprogramming, earned Shinya Yamanaka and John Gurdon the Nobel Prize in Physiology or Medicine 2012.[19] This was then followed in 2007 by the successful induction of human iPSCs derived from human dermal fibroblasts using methods similar to those used for the induction of mouse cells.[20] These induced cells exhibit similar traits to those of embryonic stem cells (ESCs) but do not require the use of embryos. Some of the similarities between ESCs and iPSCs include pluripotency, morphology, self-renewal ability, a trait that implies that they can divide and replicate indefinitely, and gene expression.[21]

Epigenetic factors are also thought to be involved in the actual reprogramming of somatic cells in order to induce pluripotency. It has been theorized that certain epigenetic factors might actually work to clear the original somatic epigenetic marks in order to acquire the new epigenetic marks that are part of achieving a pluripotent state. Chromatin is also reorganized in iPSCs and becomes like that found in ESCs in that it is less condensed and therefore more accessible. Euchromatin modifications are also common which is also consistent with the state of euchromatin found in ESCs.[21]

Due to their great similarity to ESCs, iPSCs have been of great interest to the medical and research community. iPSCs could potentially have the same therapeutic implications and applications as ESCs but without the controversial use of embryos in the process, a topic of great bioethical debate. In fact, the induced pluripotency of somatic cells into undifferentiated iPS cells was originally hailed as the end of the controversial use of embryonic stem cells. However, iPSCs were found to be potentially tumorigenic, and, despite advances,[16] were never approved for clinical stage research in the United States. Setbacks such as low replication rates and early senescence have also been encountered when making iPSCs,[22] hindering their use as ESCs replacements.

Additionally, it has been determined that the somatic expression of combined transcription factors can directly induce other defined somatic cell fates (transdifferentiation); researchers identified three neural-lineage-specific transcription factors that could directly convert mouse fibroblasts (skin cells) into fully functional neurons.[23] This result challenges the terminal nature of cellular differentiation and the integrity of lineage commitment; and implies that with the proper tools, all cells are totipotent and may form all kinds of tissue.

Some of the possible medical and therapeutic uses for iPSCs derived from patients include their use in cell and tissue transplants without the risk of rejection that is commonly encountered. iPSCs can potentially replace animal models unsuitable as well as in-vitro models used for disease research.[24]

Recent findings with respect to epiblasts before and after implantation have produced proposals for classifying pluripotency into two distinct phases: "naive" and "primed".[25] The baseline stem cells commonly used in science that are referred as Embryonic stem cells (ESCs) are derived from a pre-implantation epiblast; such epiblast is able to generate the entire fetus, and one epiblast cell is able to contribute to all cell lineages if injected into another blastocyst. On the other hand, several marked differences can be observed between the pre- and post-implantation epiblasts, such as their difference in morphology, in which the epiblast after implantation changes its morphology into a cup-like shape called the "egg cylinder" as well as chromosomal alteration in which one of the X-chromosomes undergoes random inactivation in the early stage of the egg cylinder, known as X-inactivation.[26] During this development, the egg cylinder epiblast cells are systematically targeted by Fibroblast growth factors, Wnt signaling, and other inductive factors via the surrounding yolk sac and the trophoblast tissue,[27] such that they become instructively specific according to the spatial organization.[28] Another major difference that was observed, with respect to cell potency, is that post-implantation epiblast stem cells are unable to contribute to blastocyst chimeras,[29] which distinguishes them from other known pluripotent stem cells. Cell lines derived from such post-implantation epiblasts are referred to as epiblast-derived stem cells which were first derived in laboratory in 2007; it should be noted, despite their nomenclature, that both ESCs and EpiSCs are derived from epiblasts, just at difference phases of development, and that pluripotency is still intact in the post-implantation epiblast, as demonstrated by the conserved expression of Nanog, Fut4, and Oct-4 in EpiSCs,[30] until somitogenesis and can be reversed midway through induced expression of Oct-4.[31]

Multipotency describes progenitor cells which have the gene activation potential to differentiate into discrete cell types. For example, a multipotent blood stem cell is a hematopoietic celland this cell type can differentiate itself into several types of blood cell types like lymphocytes, monocytes, neutrophils, etc., but cannot differentiate into brain cells, bone cells or other non-blood cell types.

New research related to multipotent cells suggests that multipotent cells may be capable of conversion into unrelated cell types. In another case, human umbilical cord blood stem cells were converted into human neurons.[32] Research is also focusing on converting multipotent cells into pluripotent cells.[33]

Multipotent cells are found in many, but not all human cell types. Multipotent cells have been found in cord blood,[34] adipose tissue,[35] cardiac cells,[36] bone marrow, and mesenchymal stem cells (MSCs) which are found in the third molar.[37]

MSCs may prove to be a valuable source for stem cells from molars at 810 years of age, before adult dental calcification. MSCs can differentiate into osteoblasts, chondrocytes, and adipocytes.[38]

In biology, oligopotency is the ability of progenitor cells to differentiate into a few cell types. It is a degree of potency. Examples of oligopotent stem cells are the lymphoid or myeloid stem cells.[1] A lymphoid cell specifically, can give rise to various blood cells such as B and T cells, however, not to a different blood cell type like a red blood cell.[39] Examples of progenitor cells are vascular stem cells that have the capacity to become both endothelial or smooth muscle cells.

In cell biology, a unipotent cell is the concept that one stem cell has the capacity to differentiate into only one cell type. It is currently unclear if true unipotent stem cells exist. Hepatoblasts, which differentiate into hepatocytes (which constitute most of the liver) or cholangiocytes (epithelial cells of the bile duct), are bipotent.[40] A close synonym for unipotent cell is precursor cell.

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Science Daily

Engineering human stem cells to model the kidney's filtration barrier on a chip Science Daily ... of kidney diseases and drug toxicities, and the stem cell-derived kidney podocytes we developed could even offer a new injectable cell therapy approach for regenerative medicine in patients with life-threatening glomerulopathies in the future ...

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Stem cell therapy is a type of cell therapy wherein cells are introduced into the damaged tissue so as to treat the disorder or the injury. There are a number of medical researchers who believes that the stem cell therapy has the potential to change the treatment of human diseases and reduce the suffering people face when they have a disease. They believe that there are a lot of potential to replace the damaged and diseased tissues in the body without getting the risk of rejections.

The stem cells have the ability to self-renew and also give rise to further generation of cells that can multiply. There are a number of stem cell therapies that do exist but most of them are still in the experimental stages. The treatments are very costly with an exception of bone marrow transplant. However, researchers believe that one day they will be able to develop technologies from embryonic stem cells and also adult stem cells to cure type I diabetes, cancer, Parkinsons disease, cardiac failure, neurological disorders and many more such ailments.

The stem cell therapy however carries its own pros and cons and like any other therapy it cannot be said that the stem cell therapy is an advantageous package. Here are some of the pros and cons of the therapy.

Pros of the stem cell therapy include:

It offers a lot of medical benefits in the therapeutic sectors of regenerative medicine and cloning.

It shows great potential in the treatment of a number of conditions like Parkinsons disease, spinal cord injuries, Alzheimers disease, schizophrenia, cancer, diabetes and many others.

It helps the researchers know more about the growth of human cells and their development.

In future, the stem cell research can allow the scientists to test a number of potential medicines and drugs without carrying out any test on animals and humans. The drug can be tested on a population of cells directly.

The stem cell therapy also allows researchers to study the developmental stages that cannot be known directly through the human embryo and can be used in the treatment of a number of birth defects, infertility problems and also pregnancy loss. A higher understanding will allow the treatment of the abnormal development in the human body.

The stem cell therapy puts into use the cells of the patients own body and hence the risk of rejection can be reduced because the cells belong to the same human body.

The cons of the stem cell therapy include the following:

The use of the stem cells for research involves the destruction of the blastocytes that are formed from the laboratory fertilization of the human egg.

The long term side effects of the therapy are still unknown.

The disadvantage of adult stem cells is that the cells of a particular origin would generate cells only of that type, like brain cells would generate only brain cells and so on.

If the cells used in the therapy are embryonic then the disadvantage is that the cells will not be from the same human body and there are chances of rejection.

The stem cell therapy is still under the process of research and there are a number of things that needs to be established before it used as a treatment line.

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Harvard Gazette

Researchers work to create kidney filtration barrier on a chip ... Harvard Gazette Researchers say their glomerulus-on-a-chip lined by human stem cell-derived kidney cells could help model patient-specific kidney diseases and guide ... and more »

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Shinya Yamanaka ( , Yamanaka Shin'ya?, born September 4, 1962) is a Japanese Nobel Prize-winning stem cell researcher.[1][2][3] He serves as the director of Center for iPS Cell (induced Pluripotent Stem Cell) Research and Application and a professor at the Institute for Frontier Medical Sciences(ja) at Kyoto University; as a senior investigator at the UCSF-affiliated J. David Gladstone Institutes in San Francisco, California; and as a professor of anatomy at University of California, San Francisco (UCSF). Yamanaka is also a past president of the International Society for Stem Cell Research (ISSCR).

He received the 2010 BBVA Foundation Frontiers of Knowledge Award in Biomedicine category. Also he received the Wolf Prize in Medicine in 2011 with Rudolf Jaenisch;[6] the Millennium Technology Prize in 2012 together with Linus Torvalds. In 2012 he and John Gurdon were awarded the Nobel Prize for Physiology or Medicine for the discovery that mature cells can be converted to stem cells.[7] In 2013 he was awarded the $3 million Breakthrough Prize in Life Sciences for his work.

Yamanaka was born in Higashisaka Japan in 1962. After graduating from Tennji High School attached to Osaka Kyoiku University,[8] he received his M.D. at Kobe University in 1987 and his PhD at Osaka City University Graduate School in 1993. After this, he went through a residency in orthopedic surgery at National Osaka Hospital and a postdoctoral fellowship at the Gladstone Institute of Cardiovascular Disease, San Francisco.

Afterwards he worked at the Gladstone Institutes in San Francisco, USA and Nara Institute of Science and Technology in Japan. Yamanaka is currently a Professor at Kyoto University, where he directs its Center for iPS Research and Application. He is also a senior investigator at the Gladstone Institutes as well as the director of the Center for iPS Cell Research and Application(ja).[9]

Between 1987 and 1989, Yamanaka was a resident in orthopedic surgery at the National Osaka Hospital. His first operation was to remove a benign tumor from his friend Shuichi Hirata, a task he could not complete after one hour when a skilled surgeon would have taken ten minutes or so. Some seniors referred to him as "Jamanaka", a pun on the Japanese word for obstacle.[10]

From 1993 to 1996, he was at the Gladstone Institute of Cardiovascular Disease. Between 1996 and 1999, he was an assistant professor at Osaka City University Medical School, but found himself mostly looking after mice in the laboratory, not doing actual research.[10]

His wife advised him to become a practicing doctor, but instead he applied for a position at the Nara Institute of Science and Technology. He stated that he could and would clarify the characteristics of embryonic stem cells, and this can-do attitude won him the job. From 19992003, he was an associate professor there, and started the research that would later win him the 2012 Nobel Prize. He became a full professor and remained at the institute in that position from 20032005. Between 2004 and 2010, Yamanaka was a professor at the Institute for Frontier Medical Sciences.[11] Currently, Yamanaka is the director and a professor at the Center for iPS Cell Research and Application at Kyoto University.

In 2006, he and his team generated induced pluripotent stem cells (iPS cells) from adult mouse fibroblasts.[1] iPS cells closely resemble embryonic stem cells, the in vitro equivalent of the part of the blastocyst (the embryo a few days after fertilization) which grows to become the embryo proper. They could show that his iPS cells were pluripotent, i.e. capable of generating all cell lineages of the body. Later he and his team generated iPS cells from human adult fibroblasts,[2] again as the first group to do so. A key difference from previous attempts by the field was his team's use of multiple transcription factors, instead of transfecting one transcription factor per experiment. They started with 24 transcription factors known to be important in the early embryo, but could in the end reduce it to 4 transcription factors Sox2, Oct4, Klf4 and c-Myc.[1]

Yamanaka practiced judo (2nd Dan black belt) and played rugby as a university student. He also has a history of running marathons. After a 20-year gap, he competed in the inaugural Osaka Marathon in 2011 as a charity runner with a time of 4:29:53. He also took part in the 2012 Kyoto Marathon to raise money for iPS research, finishing in 4:03:19. He also ran in the second Osaka Marathon on November 25, 2012.[12]

In 2007, Yamanaka was recognized as a "Person Who Mattered" in the Time Person of the Year edition of Time Magazine.[13] Yamanaka was also nominated as a 2008 Time 100 Finalist.[14] In June 2010, Yamanaka was awarded the Kyoto Prize for reprogramming adult skin cells to pluripotential precursors. Yamanaka developed the method as an alternative to embryonic stem cells, thus circumventing an approach in which embryos would be destroyed.

In May 2010, Yamanaka was given "Doctor of Science honorary degree" by Mount Sinai School of Medicine.[15]

In September 2010, he was awarded the Balzan Prize for his work on biology and stem cells.[16]

Yamanaka has been listed as one of the 15 Asian Scientists To Watch by Asian Scientist magazine on May 15, 2011.[17][18] In June 2011, he was awarded the inaugural McEwen Award for Innovation; he shared the $100,000 prize with Kazutoshi Takahashi(ja), who was the lead author on the paper describing the generation of induced pluripotent stem cells.[19]

In June 2012, he was awarded the Millennium Technology Prize for his work in stem cells.[20] He shared the 1.2 million euro prize with Linus Torvalds, the creator of the Linux kernel.

In October 2012, he and fellow stem cell researcher John Gurdon were awarded the Nobel Prize in Physiology or Medicine "for the discovery that mature cells can be reprogrammed to become pluripotent."[21]

The 2012 Nobel Prize in Physiology or Medicine was awarded jointly to Sir John B. Gurdon and Shinya Yamanaka "for the discovery that mature cells can be reprogrammed to become pluripotent."[22]

There are different types of stem cells

. These are some types of cells that will help in understanding the material.

totipotency remains through the first few cell divisions ex. the fertilised egg

The early embryo consists mainly of pluripotent stem cells

ex) blood multipotent cells can develop into various blood cells

Theoretically patient-specific transplantations possible

Much research done Immune rejection reducible via stem cell bank

Pluripotent

Abnormal aging

No immune rejection Safe (clinical trials)

The prevalent view during the early 20th century was that mature cells were permanently locked into the differentiated state and cannot return to a fully immature, pluripotent stem cell state. They thought that cellular differentiation can only be a unidirectional process. Therefore, non-differentiated egg/early embryo cells can only develop into specialized cells. However, stem cells with limited potency (adult stem cells) remain in bone marrow, intestine, skin etc. to act as a source of cell replacement.[23]

The fact that differentiated cell types had specific patterns of proteins suggested irreversible epigenetic modifications or genetic alterations to be the cause of unidirectional cell differentiation. So, cells progressively become more restricted in the differentiation potential and eventually lose pluripotency.[24]

In 1962, John B. Gurdon demonstrated that the nucleus from a differentiated frog intestinal epithelial cell can generate a fully functional tadpole via transplantation to an enucleated egg. Gurdon used somatic cell nuclear transfer (SCNT) as a method to understand reprogramming and how cells change in specialization. He concluded that differentiated somatic cell nuclei had the potential to revert to pluripotency. This was a paradigm shift during the time. It showed that a differentiated cell nucleus has retained the capacity to successfully revert to an undifferentiated state, with the potential to restart development (pluripotent capacity).

However, the question still remained whether an intact differentiated cell could be fully reprogrammed to become pluripotent.

Shinya Yamanaka proved that introduction of a small set of transcription factors into a differentiated cell was sufficient to revert the cell to a pluripotent state. Yamanaka focused on factors that are important for maintaining pluripotency in embryonic stem (ES) cells. Knowing that transcription factors were involved in the maintenance of the pluripotent state, he selected a set of 24 ES cell transcriptional factors as candidates to reinstate pluripotency in somatic cells.

First, he collected the 24 candidate factors. When all 24 genes encoding these transcription factors were introduced into skin fibroblasts, few actually generated colonies that were remarkably similar to ES cells. Secondly, further experiments were conducted with smaller numbers of transcription factors added to identify the key factors, through a very simple and yet sensitive assay system. Lastly, he identified the four key factors. They found that 4 transcriptional factors (Myc, Oct3/4, Sox2 and Klf4) were sufficient to convert mouse embryonic or adult fibroblasts to pluripotent stem cells (capable of producing teratomas in vivo and contributing to chimeric mice).

These pluripotent cells are called iPS (induced pluripotent stem) cells; they appeared with very low frequency.

iPS cells can be selected by inserting the b-geo gene into the Fbx15 locus. The Fbx15 promoter is active in pluripotent stem cells which induce b-geo expression, which in turn gives rise to G418 resistance; this resistance helps us identify the iPS cells in a culture.

Moreover, in 2007, Yamanaka and his colleagues found iPS cells with germ line transmission (via selecting for Oct4 or Nanog gene). Also in 2007, they were the first to produce human iPS cells.

However, there are some difficulties to overcome. The first is the issue of the very low production rate of iPS cells, and the other is the fact that the 4 transcriptional factors are shown to be oncogenic.

Nonetheless, this is a truly fundamental discovery. This was the first time an intact differentiated somatic cell could be reprogrammed to become pluripotent. This opened up a completely new research field.

In July 2014, a scandal regarding the research of Haruko Obokata was connected to Yamanaka. He could not find the lab notes from the period in question [25] and was made to apologise.[26][27]

Since the original discovery by Yamanaka, much further research has been done in this field, and many improvements have been made to the technology. Here we[who?] discuss the improvements made to Yamanaka's research as well as the future prospects of his findings.

1. The delivery mechanism of pluripotency factors has been improved. At first retroviral vectors, that integrate randomly in the genome and cause deregulation of genes that contribute to tumor formation, were used. However, now, non-integrating viruses, stabilised RNAs or proteins, or episomal plasmids (integration-free delivery mechanism) are used.

2. Transcription factors required for inducing pluripotency in different cell types have been identified (e.g. neural stem cells).

3. Small substitutive molecules were identified, that can substitute for the function of the transcription factors.

4. Transdifferentiation experiments were carried out. They tried to change the cell fate without proceeding through a pluripotent state. They were able to systematically identify genes that carry out transdifferentiation using combinations of transcription factors that induce cell fate switches. They found trandifferentiation within germ layer and between germ layers, e.g., exocrine cells to endocrine cells, fibroblast cells to myoblast cells, fibroblast cells to cardiomyocyte cells, fibroblast cells to neurons

5. Cell replacement therapy with iPS cells is a possibility. Stem cells can replace diseased or lost cells in degenerative disorders and they are less prone to immune rejection. However, there is a danger that it may introduce mutations or other genomic abnormalities that render it unsuitable for cell therapy. So, there are still many challenges, but it is a very exciting and promising research area. Further work is required to guarantee safety for patients.

6. Can medically use iPS cells from patients with genetic and other disorders to gain insights into the disease process. - Amyotrophic lateral sclerosis (ALS), Rett syndrome, spinal muscular atrophy (SMA), 1-antitrypsin deficiency, familial hypercholesterolemia and glycogen storage disease type 1A. - For cardiovascular disease, Timothy syndrome, LEOPARD syndrome, type 1 and 2 long QT syndrome - Alzheimers, Spinocerebellar ataxia, Huntingtons etc.

7. iPS cells provide screening platforms for development and validation of therapeutic compounds. For example, kinetin was a novel compound found in iPS cells from familial dysautonomia and beta blockers & ion channel blockers for long QT syndrome were identified with iPS cells.

Yamanaka's research has opened a new door and the world's scientists have set forth on a long journey of exploration, hoping to find our cells true potential.[28]

In 2013, iPS cells were used to generate a human vascularized and functional liver in mice in Japan. Multiple stem cells were used to differentiate the component parts of the liver, which then self-organized into the complex structure. When placed into a mouse host, the liver vessels connected to the hosts vessels and performed normal liver functions, including breaking down of drugs and liver secretions. [29]

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Induced pluripotent stem cells have revolutionized stem cell science in the decade since their invention. Theyre yielding clues into the nature of diseases such as cancer and Alzheimers, and are also being tapped for therapy.

But creating these IPS cells is lengthy, complicated and tricky, and the facilities equipped to make them cant accommodate all the scientists whod like to get their hands on them.

A UK-led consortium has removed that bottleneck, by producing 711 lines of ready-to-go IPS cells from healthy individuals. These lines are meant to help scientists understand the normal variations between healthy individuals and those involved in disease, as well as to understand normal human biology and development.

The IPS lines are available for research purposes to academic scientists and industry by contacting the Human Induced Pluripotent Stem Cell Initiative (HipSci), at http://www.hipsci.org and the European Bank for induced Pluripotent Stem Cells at https://www.ebisc.org.

The accomplishment was announced in a study published in Nature. It can be found online at j.mp/711ips.

While many other efforts have generated IPS cells to address rare diseases, this study produces them from healthy volunteers to plumb common genetic variation, Fiona Watt, a lead author on the paper and co-principal investigator of HipSci, from King's College London, said in a statement.

"We were able to show similar characteristics of iPS cells from the same person, and revealed that up to 46 per cent of the differences we saw in iPS cells were due to differences between individuals, Watt said in the statement. These data will allow researchers to put disease variations in context with healthy people."

Andrs Bratt-Leal, director of the Parkinson's Cell Therapy Program at The Scripps Research Institute in La Jolla, agreed.

This kind of study is extremely important because it leads to a deeper understanding of the differences between normal genetic variation and genetic changes that could negatively impact cell behavior, said Bratt-Leal, who was not involved in the study.

This data will help scientists using induced pluripotent stem cells to model diseases as well as scientists developing cell therapies, said Bratt-Leal, who works in the lab of stem cell researcher Jeanne Loring.

Because DNA sequencing has become a routine tool in the lab, enormous amounts of data have been produced, he said. Not only have we have observed a high level of genetic diversity between different people, but also a more subtle variation exists among the cells from an individual person. The next step is a better understanding of how this diversity translates to function and behavior of stem cells and mature cells derived from stem cells.

Loring and Bratt-Leal are studying the use of induced pluripotent stem cells to relieve symptoms of Parkinsons disease. They are in the process of translating the research into a therapy, aided with a grant from the California Institute for Regenerative Medicine.

The work was the product of a large-scale collaboration of scientists from various institutions in the United Kingdom, including the European Molecular Biology Laboratory in Cambridge; Wellcome Trust Sanger Institute in Cambridge; the University of Dundee in Dundee; and the University of Cambridge. Also participating was St Vincent's Institute of Medical Research in Victoria, Australia.

bradley.fikes@sduniontribune.com

(619) 293-1020

UPDATES:

1:00 p.m.: This article was updated with additional details.

This article was originally published at 10:00 a.m.

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Hundreds of new stem cell lines ready to help research - The San Diego Union-Tribune

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The kidney is made up of about a million tiny units that filter blood, rid the body of undesired waste products while holding back blood cells and valuable proteins, and control the bodys fluid content. Key to each of these units is a structure known the glomerulus, in which podocyte cells wrap themselves tightly around a tuft of capillaries separated only by a thin membrane composed of extracellular matrix, and leave slits between them to build an actual filtration barrier. Podocytes are the target of many congenital or acquired kidney diseases, and they are often harmed by drugs.

To build an in vitro model of the human glomerulus to probe deeper into its function and vulnerabilities to disease and drug toxicities, researchers have been attempting to engineer human stem cells that in theory can give rise to any mature cell type so that they form into functional podocytes. These cell culture efforts, however, so far have failed to produce populations of mature podocytes pure enough as to be useful for modeling glomerular filtration.

A team led by Donald Ingber, Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and Founding Director of Harvards Wyss Institute of Biologically Inspired Engineering, now reports a solution to this challenge in Nature Biomedical Engineering, which enables the differentiation of human induced pluripotent stem (iPS) cells into mature podocytes with more than 90 percent efficiency.

Linking the differentiation process with organ-on-a-chip technology pioneered by his team, the researchers went on to engineer the first in vitro model of the human glomerulus, demonstrating effective and selective filtration of blood proteins and podocyte toxicity induced by a chemotherapy drug in vitro.

Ingber is also theJudah Folkman Professor of Vascular Biologyat Harvard Medical School (HMS) and the Vascular Biology Program at Boston Childrens Hospital.

The development of a functional human kidney glomerulus chip opens up an entirely new experimental path to investigate kidney biology, carry out highly personalized modeling of kidney diseases and drug toxicities, and the stem cell-derived kidney podocytes we developed could even offer a new injectable cell therapy approach for regenerative medicine in patients with life-threatening glomerulopathies in the future, said Ingber.

Ingbers team has engineered multiple organs-on-chips that accurately mimic human tissue and organ-level physiology. These platforms are currently being evaluated by the Food and Drug Administration (FDA) as a tool to more effectively study the effects of potential chemical and biological hazards found in foods, cosmetics or dietary supplementsthan existing culture systems or animal models. In 2013, his team developed an organ-on-a-chip microfluidic culture device that modeled the human kidneys proximal tubule, which is anatomically connected to the glomerulus and salvages ions from urinary fluid.

Now, with the teams newly engineered human kidney glomerulus-on-a-chip, researchers also can get in vitro access to the kidneys core filtration mechanisms that are critical for drug clearance and pharmacokinetics, in addition to studying human podocytes at work.

To generate almost pure populations of human podocytes in cell culture, Samira Musah, the studys first author and HMS Deans Postdoctoral Fellow who is working with Ingber at the Wyss Institute, leveraged pieces of the stem cell biologists arsenal, and merged them with snippets taken from Ingbers past research on how cells in the body respond to adhesive factors and physical forces in their tissue environments.

Our method not only uses soluble factors that guide kidney development in the embryo but, by growing and differentiating stem cells on extracellular matrix components that are also contained in the membrane separating the glomerular blood and urinary systems, we more closely mimic the natural environment in which podocytes are induced and mature, said Musah. We even succeeded in inducing much of this differentiation process within a channel of the microfluidic chip, whereby applying cyclical motions that mimic the rhythmic deformations living glomeruli experience due to pressure pulses generated by each heartbeat, we achieve even greater maturation efficiencies.

The complete microfluidic system closely resembles a living, three-dimensional cross-section of the human glomerular wall. It consists of an optically clear, flexible, polymeric material the size of a computer memory chip in which two closely opposed microchannels are separated by a porous, extracellular matrix-coated membrane that corresponds to the kidneys glomerular basement membrane. In one of the membrane-facing channels, the researchers grow glomerular endothelial cells to mimic the blood microvessel compartment of glomeruli. The iPS cells are cultured on the opposite side of the membrane in the other channel that represents the glomerulus urinary compartment, where they are induced to form a layer of mature podocytes that extend long cellular processes through the pores in the membrane and contact the underlying endothelial cells. In addition, the devices channels are rhythmically stretched and relaxed at a rate of one heart beat per second by applying cyclic suction to hollow chambers placed on either side of the cell-lined microchannels to mimic physiological deformations of the glomerular wall.

This in vitro system allows us to effectively recapitulate the filtration of small substances contained in blood into the urinary compartment while retaining large proteins in the blood compartment just like in our bodies, and we can visualize and monitor the damage inflicted by drugs that cause breakdown of the filtration barrier in the kidney, said Musah.

The study was also co-authored by Wyss Institute Core Faculty member George Church, who also is Professor of Genetics at HMS and Professor of Health Sciences and Technology at Harvard and the Massachusetts Institute of Technology (MIT), and who served as a co-mentor of Musah with Ingber. Other authors include Akiko Mammoto and Tadanori Mammoto, who at the time of the study were Instructors in the Vascular Biology Program and Department of Surgery at Boston Childrens Hospital, as well as Thomas Ferrante, Sauveur Jeanty, Kristen Roberts, Seyoon Chung, Richard Novak, Miles Ingram, Tohid Fatanat-Didar, Sandeep Koshy, and James Weaver.

Funding for the study was provided by the Defense Advanced Research Projects Agency (DARPA). Musah was supported by a HMS Deans Postdoctoral Fellowship, Postdoctoral Enrichment Program Award from the Burroughs Wellcome Fund, UNCF-Merck Postdoctoral Fellowship, and an NIH/NIDDK Nephrology Training Grant.

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Engineering human stem cells to model the kidney's filtration barrier on a chip - Harvard School of Engineering and Applied Sciences

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CAMBRIDGE, Mass. and CROMWELL, Conn., May 04, 2017 (GLOBE NEWSWIRE) -- Cellaria, LLC, a scientific innovator that develops revolutionary new patient-specific models for challenging diseases, and Biological Industries USA (BI-USA), a subsidiary of Biological Industries (Israel), today announced a new sales and marketing agreement to promote custom stem cell services. The partnership combines BI-USAs strength in stem cell culture media and manufacturing with Cellarias comprehensive Stem Cell Services program, which includes industry leading RNA reprogramming and custom differentiation services. Together, the companies will offer one of the industrys most innovative and comprehensive stem cell service offerings available to biotechnology companies and academic institutions.

As part of the agreement, Cellaria will distribute BI-USAs stem cell media offering, including its NutriStem hPSC Medium, a cGMP xeno-free media specifically designed for human pluripotent stem cell culture. Cellaria will also incorporate the product into its stem cell services. BI-USA will market Cellaria's customized stem cell services, establishing an integrated, single source solution for iPS cell line derivation, culture maintenance, banking, characterization and differentiation services.

BI is one of the most respected names in life sciences today, said David Deems, chief executive officer at Cellaria. The companys strong market presence and innovative media products will enhance our stem cell and RNA reprogramming service offerings and significantly increase the availability and appeal of our combined offerings.

This is an important partnership for us, added Tanya Potcova, chief executive officer of BI-USA. In combination, our teams bring a wealth of stem cell experience but also share a common goal of creating higher quality, more consistent research outcomes for researchers in the life sciences field. We are pleased to be working with the team at Cellaria to put the best possible tools and support in the hands of our present and future customers.

Please visit Cellaria and BI at the International Society of Stem Cell Research Annual Meeting in Boston, MA June 14-17, 2017 at booth# 407.

About Cellaria Cellaria creates high quality, next generation in vitro disease models that reflect the unique nature of a patients biology. All models begin with tissue from a patient, capturing clinically relevant details that inform model characterization. For cancer, Cellarias cell models exhibit molecular and phenotypic characteristics that are highly concordant to the patient. For RNA-mediated iPS cell line derivation and stem cell services, Cellarias cell models enable interrogation of patient and disease-specific mechanisms of action. Cellarias innovative products and services help lead the research community to more personalized therapeutics, revolutionizing and accelerating the search for a cure. For more information, visitwww.cellariabio.com.

About Biological Industries Biological Industries (BI) is one of the worlds leading and trusted suppliers to the life sciences industry, with over 35 years experience in cell culture media development and cGMP manufacturing. BIs products range from classical cell culture media to supplements and reagents for stem cell research and potential cell therapy applications, to serum-free, xeno-free media. BI is committed to a Culture of Excellence through advanced manufacturing and quality-control systems, regulatory expertise, in-depth market knowledge, and extensive technical customer-support, training, and R&D capabilities.

Biological Industries USA (BI-USA) is the US commercialization arm of BI, with facilities in Cromwell, Connecticut. Members of the BI-USA team share a history and expertise of innovation and success in the development of leading-edge technologies in stem cell research, cellular reprogramming, and regenerative medicine. For more information, visit http://www.bioind.com or connect onLinkedIn,Twitter, andFacebook.

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Cellaria and Biological Industries USA Partner on Stem Cell Media ... - Yahoo Finance

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Colorado State University is one of multiple research institutions that uses stem cells from aborted fetal tissue to research HIV and AIDS, a practice some say is unnecessary and immoral, but researchers say is essential.

Emily Faulkner, a senior biology major at CSU and founder of the anti-abortion group, CSU Students for Life, has been advocating against the Universitys use of fetal tissue for moral and legal reasons. Faulkner believes the University has illegally obtained fetal tissue for research and still could be after similar allegations against Planned Parenthood and CSU arose in 2015.

Earlier this semester, Faulkner hung posters that said CSU buys trafficked baby parts but says they were ripped down an hour later.

For a community that expresses tolerance for (many other communities) it seems to be very intolerant of the pro-life community, Faulkner said. Its really hard to open peoples minds to actually see whats going on, especially when theres so much intolerance.

In January, a Republican panel from the House of Representatives released a report suggesting some Planned Parenthood clinics and firms sold fetal tissue for profit, which is illegal under federal law. The report concluded over a year-long investigation after similar allegations against Planned Parenthood arose in 2015.

The report cited documents indicating the University paid the tissue procurement organizations StemExpress and Advanced Bioscience Resources $2,000 and $100,000, respectively, for fetal tissue between 2010 and 2015. It is illegal to buy fetal tissue, but federal law does not specify how much can be charged for shipping and handling. The report questions whether or not ABR and StemExpress donated the fetal tissue or sold it for profit.

Faulkner brought up CSUs use of fetal tissue this semester in response to the report. She and CSU Students for Life collected signatures on a petition that asked CSU President Tony Frank to investigate whether or not CSU was involved in illegal obtainment of fetal tissue and to acknowledge its use in research.

In response to the 2015 allegations, Frank wrote to Rep. Doug Lamborn stating that CSU was compliant with all state and federal laws in acquiring fetal tissue. According to Executive Director of Public Affairs and Communications, Mike Hooker, and the Vice President for Research, Alan Rudolph, the University has continued to follow the state and federal laws.

(Part of) my job as an institutional official is making sure that we sustain the highest standards for practice even beyond what the feds recommend, Rudolph said.

In addition to legal concerns, Faulkner also has moral concerns. She said that though abortion may be legal, that does not mean it is right. She expressed concern about fetal tissue and organs being harvested from late-term fetuses with beating hearts.

Its quite inhumane, Faulkner said. Were talking about actual human beings that have livers, brains and hearts. Theyre actually living, breathing beings.

Faulkner said fetal tissue should not be necessary for research on curing or preventing HIV and AIDS, as there is also gene replacement therapy, which takes HIV out of infected cells, and pre-exposure prophylaxis treatment, which consists of taking a pill daily to prevent HIV. Faulkner also said that researchers could use induced pluripotent stem cells (iPS cells) created from adult cells instead of stem cells from fetal tissue.

Pluripotent cells have the ability to become any cell in the body. However, according to Rudolph, iPS stem cells from adults cannot be used in CSUs research on curing and bettering HIV and AIDS, which is conducted by CSU virology professor Ramesh Akkina.

Fetal tissue research, especially the work that Ramesh does, cannot currently be done any other way, Rudolph said.

Akkina uses stem cells from fetal tissue to recreate human immune systems in mice, which Rudolph said are multicellular systems. Akkinas humanized mice can be used to study the effects of countermeasures, including therapeutics, antibodies, vaccines or biologics, on a human immune system meant to improve or cure HIV.

Rudolph said that while scientists are looking into how to conduct research on HIV and AIDS using iPS stem cells, the cells are more limited in their ability to create other types of cells than stem cells from fetal tissue are. He said that cells from fetal tissue are so far back in their development that they have the ability to create complex functions that are lost when cells become older. Cells are more pluripotent.

Faulkner said she hopes that scientists research and work with iPS stem cells.

The lives of those affected by HIV/AIDS are very important, but so are the lives of the unborn, Faulkner wrote in a message to the Collegian. We cannot forget equality for all.

Collegian reporter MQ Borocz can be reached at news@collegian.com or on Twitter @MQBorocz22.

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CSU's use of fetal tissue for HIV/AIDS research sparks controversy - Rocky Mountain Collegian

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Thursday, May 4, 2017 11:31 AM UTC

CAMBRIDGE, Mass. and CROMWELL, Conn., May 04, 2017 -- Cellaria, LLC, a scientific innovator that develops revolutionary new patient-specific models for challenging diseases, and Biological Industries USA (BI-USA), a subsidiary of Biological Industries (Israel), today announced a new sales and marketing agreement to promote custom stem cell services. The partnership combines BI-USAs strength in stem cell culture media and manufacturing with Cellarias comprehensive Stem Cell Services program, which includes industry leading RNA reprogramming and custom differentiation services. Together, the companies will offer one of the industrys most innovative and comprehensive stem cell service offerings available to biotechnology companies and academic institutions.

As part of the agreement, Cellaria will distribute BI-USAs stem cell media offering, including its NutriStem hPSC Medium, a cGMP xeno-free media specifically designed for human pluripotent stem cell culture. Cellaria will also incorporate the product into its stem cell services. BI-USA will market Cellaria's customized stem cell services, establishing an integrated, single source solution for iPS cell line derivation, culture maintenance, banking, characterization and differentiation services.

BI is one of the most respected names in life sciences today, said David Deems, chief executive officer at Cellaria. The companys strong market presence and innovative media products will enhance our stem cell and RNA reprogramming service offerings and significantly increase the availability and appeal of our combined offerings.

This is an important partnership for us, added Tanya Potcova, chief executive officer of BI-USA. In combination, our teams bring a wealth of stem cell experience but also share a common goal of creating higher quality, more consistent research outcomes for researchers in the life sciences field. We are pleased to be working with the team at Cellaria to put the best possible tools and support in the hands of our present and future customers.

Please visit Cellaria and BI at the International Society of Stem Cell Research Annual Meeting in Boston, MA June 14-17, 2017 at booth# 407.

About Cellaria Cellaria creates high quality, next generation in vitro disease models that reflect the unique nature of a patients biology. All models begin with tissue from a patient, capturing clinically relevant details that inform model characterization. For cancer, Cellarias cell models exhibit molecular and phenotypic characteristics that are highly concordant to the patient. For RNA-mediated iPS cell line derivation and stem cell services, Cellarias cell models enable interrogation of patient and disease-specific mechanisms of action. Cellarias innovative products and services help lead the research community to more personalized therapeutics, revolutionizing and accelerating the search for a cure. For more information, visitwww.cellariabio.com.

About Biological Industries Biological Industries (BI) is one of the worlds leading and trusted suppliers to the life sciences industry, with over 35 years experience in cell culture media development and cGMP manufacturing. BIs products range from classical cell culture media to supplements and reagents for stem cell research and potential cell therapy applications, to serum-free, xeno-free media. BI is committed to a Culture of Excellence through advanced manufacturing and quality-control systems, regulatory expertise, in-depth market knowledge, and extensive technical customer-support, training, and R&D capabilities.

Biological Industries USA (BI-USA) is the US commercialization arm of BI, with facilities in Cromwell, Connecticut. Members of the BI-USA team share a history and expertise of innovation and success in the development of leading-edge technologies in stem cell research, cellular reprogramming, and regenerative medicine. For more information, visit http://www.bioind.com or connect onLinkedIn,Twitter, andFacebook.

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Cellaria and Biological Industries USA Partner on Stem Cell Media and Research - EconoTimes

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Details WhaTech Channel: Industrial Market Research Published: 04 May 2017 Submitted by John Vardon WhaTech Premium News from QY Research Groups Viewed: 7 times

This report studies the global Regenerative Medicine market, analyzes and researches the Regenerative Medicine development status and forecast in United States, EU, Japan, China, India and Southeast Asia.Learn details of the Size, Status and Forecast 2022

What is Regenerative Medicine?

Download Report atwww.qyresearchgroups.com/request-sample/339736

History

Applications

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This report focuses on the top players in global market, like

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Table of Contents

Global Regenerative Medicine Market Size, Status and Forecast 2022 1 Industry Overview of Regenerative Medicine 1.1 Regenerative Medicine Market Overview 1.1.1 Regenerative Medicine Product Scope 1.1.2 Market Status and Outlook 1.2 Global Regenerative Medicine Market Size and Analysis by Regions 1.2.1 United States 1.2.2 EU 1.2.3 Japan 1.2.4 China 1.2.5 India 1.2.6 Southeast Asia 1.3 Regenerative Medicine Market by Type 1.3.1 Cell Therapy 1.3.2 Tissue Engineering 1.3.3 Biomaterial 1.3.4 Others 1.4 Regenerative Medicine Market by End Users/Application 1.4.1 Dermatology 1.4.2 Cardiovascular 1.4.3 CNS

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1.4.4 Orthopedic 1.4.5 Others

2 Global Regenerative Medicine Competition Analysis by Players 2.1 Regenerative Medicine Market Size (Value) by Players (2016 and 2017) 2.2 Competitive Status and Trend 2.2.1 Market Concentration Rate 2.2.2 Product/Service Differences 2.2.3 New Entrants 2.2.4 The Technology Trends in Future

3 Company (Top Players) Profiles 3.1 Acelity 3.1.1 Company Profile 3.1.2 Main Business/Business Overview 3.1.3 Products, Services and Solutions 3.1.4 Regenerative Medicine Revenue (Value) (2012-2017) 3.1.5 Recent Developments 3.2 DePuy Synthes 3.2.1 Company Profile 3.2.2 Main Business/Business Overview 3.2.3 Products, Services and Solutions 3.2.4 Regenerative Medicine Revenue (Value) (2012-2017) 3.2.5 Recent Developments 3.3 Medtronic 3.3.1 Company Profile 3.3.2 Main Business/Business Overview

READ MORE atwww.qyresearchgroups.com/report/global-regenerative-medicine-market-size-status-and-forecast-2022

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Latest report on regenerative medicine market just published - WhaTech

IPS Cell Therapy Comments Off on Latest report on regenerative medicine market just published – WhaTech | May 4th, 2017

(EnviroNews World News) Kobe, Japan For more than two million Americans, straight lines may look wavy and the vision in the center of their eye may slowly disappear. Its called age-related macular degeneration (AMD), and there is no cure. But that may change soon.

A surgical team at Kobe City Medical Center General Hospital in Japan recently injected 250,000 retinal pigment epithelial (RPE) cells into the right eye of a man in his 60s. The cells were derived from donor stem cells stored at Kyoto University. It marked the first time that retinal cells derived from a donors skin have been implanted in a patients eye. The skin cells had been reprogrammed into induced pluripotent stem cells (iPS), which can be grown into most cell types in the body.

The procedure is part of a safety study authorized by Japans Ministry of Health that will involve five patients. Each will be followed closely for one year and continue to receive follow-up exams for three additional years. Project leader Dr. Masayo Takahashi at Riken, a research institution that is part of the study, told the Japan Times, A key challenge in this case is to control rejection. We need to carefully continue treatment.

A previous procedure on a different patient in 2014 used stem cells from the individuals own skin. Two years later, the patient reported showing some improvement in eyesight. But the procedure cost $900,000, leading the study team to move forward using donor cells. They expect the costs to come down to less than $200,000.

Among people over 50 in developed countries, AMD is the leading cause of vision loss. According to the National Eye Institute, 14 percent of white Americans age 80 or older will suffer some form of AMD. The condition is almost three times more common among white adults than among people of color. Women of all races comprise 65 percent of AMD cases.

The lack of a cure has led some to try unproven treatments. Three elderly women lost their sight after paying $5,000 each for a stem cell procedure at a private clinic in Florida. Clinic staff used liposuction to remove fat from the womens bellies. They then extracted stem cells from the fat, which were injected into both eyes of each patient in the same procedure, resulting in vision loss in both eyes. Two of the three victims agreed to a lawsuit settlement with the company that owned the clinic.

Stem cell therapy is still at an early stage. As of January 2016, 10 clinical uses have been approved around the world, all using adult stem cells. These include some forms of leukemia and bone marrow disease, Hodgkin and non-Hodgkin lymphoma and some rare inherited disorders including sickle cell anemia. Stem cell transplants are now often used to treat multiple myeloma, which strikes more than 24,000 people a year in the U.S.

Clinical trials to treat type 1 diabetes, Parkinsons disease, stroke, brain tumors and other conditions are being conducted. The first patient in a nationwide clinical study to receive stem cell therapy for heart failure recently underwent the procedure at the University of Wisconsin School of Medicine and Public Health. An experimental treatment at Keck Medical Center of USC last year on a paralyzed patient restored the 21-year-old mans use of his arms and hands. Harvard scientists see stem cell biology as a path to counter aging and extend human lifespans. But the International Society for Stem Cell Research warns that there are many challenges ahead before these treatments are proven safe and effective.

The U.S. Food and Drug Administration (FDA) regulates stem cells to ensure that they are safe and effective for their intended use. But, that doesnt stop some clinics from preying on worried patients. The FDA warns on its website that the hope that patients have for cures not yet available may leave them vulnerable to unscrupulous providers of stem cell treatments that are illegal and potentially harmful.

While there is yet no magic cure for AMD, the Japan study and others may one day lead there. The Harvard Stem Cell Institute (HSCI) in Boston is currently researching retina stem cell transplants. One approach uses gene therapy to generate a molecule that preserves healthy vision. Another involves Muller cells, which give fish the ability to repair an injured retina.

But these therapies are far off. We are at about the halfway mark, but there is still a precipitous path ahead of us, Takahashi said.

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World's 1st Stem Cell Transplant from Donor to Man's Eye Shows Promise of Restoring Sight - EnviroNews (registration) (blog)

IPS Cell Therapy Comments Off on World’s 1st Stem Cell Transplant from Donor to Man’s Eye Shows Promise of Restoring Sight – EnviroNews (registration) (blog) | April 27th, 2017

Organ transplant rejection might eventually be preventable by giving recipients an immune-suppressing vaccine derived from induced pluripotent stem cells, according to a study led by Japanese researchers.

In mice, the treatment allowed permanent acceptance of heart grafts by selectively inhibiting the immune response to the donor graft, said the study, published April 20 in Stem Cell Reports. The work might also be applicable to autoimmune diseases, the study said.

The study can be found at j.mp/ipscden. The co-first authors were Songjie Cai, Jiangang Hou, and Masayuki Fujino. The senior author was Xiao-Kang Li. All are of the National Research Institute for Child Health and Development in Tokyo.

The IPS cells were matured into donor-type regulatory dendritic cells (DCregs) which in turn caused production of tolerance-inducing regulatory T cells, or Tregs, that allow the graft to be treated as self.

While the technology looks good, a UC San Diego stem cell researcher said it faces a number of hurdles that make practical use of it difficult, especially the difficulty in producing the donor-derived regulatory cells in time to be of use in a transplant.

Use of these Tregs and immature DCregs for transplant has been investigated for several years now. In theory, they would provide a better method of preventing rejection than immunosuppressive drugs that knock down immune functioning across the board.

However, activating Tregs must be done precisely, or other T cell types will be activated, increasing the risk of rejection.

The study found that donor-type dendritic cells reliably activated Tregs and not the other types. Peptide antigens from the graft directed naive CD4+ T cells to mature into donor-specific Tregs, providing a selective immune signal to tolerate the graft.

Use of IPS cells for producing these immune regulatory cells is quite novel, said Dan Kaufman, director of cell therapy at UC San Diego, and affiliated with the universitys Sanford Stem Cell Clinical Center.

Obviously, it fits my interest in making immune cells from ES and IPS cells, Kaufman said. The ability to use these cells to suppress transplant rejection seems quite strong. I think the data is all good.

That said, the findings could be strengthened by extending the work from animals to human xenografts, he said. That would demonstrate that human IPS cells can similarly function, although it would be challenging.

Another limitation is the need to use donor-derived cells to induce immune tolerance.

How you would translate that would be unclear to me, Kaufman said.

Are you going to get a heart and then make IPS cells from that donor, which obviously you couldnt do in a reasonable time frame? Could you create a bank of these types of cells that might be suitable for certain patient populations with certain HLA types? Im not sure. I think that gets a little more speculative.

Another speculative possibility is to make the donor-derived IPS cells grow into an organ, and then also create the immune-regulating cells from these IPS cells to selectively induce tolerance.

But were still, I think, a long ways off from having IPS-derived organs, he said.

Autoimmune disease treatment with this technology is worth exploring, Kaufman said. In that case, the IPSCs would be made from the patients themselves.

More than 118,000 Americans are on the waiting list for an organ transplant, according to the Organ Procurement and Transplantation Network.

bradley.fikes@sduniontribune.com

(619) 293-1020

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Stem cell-based treatment prevents transplant rejection, in animal study - The San Diego Union-Tribune

IPS Cell Therapy Comments Off on Stem cell-based treatment prevents transplant rejection, in animal study – The San Diego Union-Tribune | April 23rd, 2017

MADISON, Wis.--(BUSINESS WIRE)--Cellular Dynamics International (CDI), a FUJIFILM company and a leading developer and manufacturer of induced pluripotent stem cells (iPS), today announced it has signed a collaboration agreement with the Harvard Stem Cell Institute (HSCI), a novel network of stem cell scientists that extends from the University to its affiliated hospitals and the biomedical industry. The objective of the new partnership is to increase the availability of iPS cells and services to the HSCI network and the research community at large.

CDI is honored and excited to partner with Harvard Stem Cell Institute, one of the worlds most prestigious research organizations, said Dr. Bruce Novich, Division President-CNBD for FUJIFILM Holdings America Corporation and Executive Vice President and General Manager of Life Science Business Division for CDI. Our goal is to make iPS cells and technology more accessible so that researchers across disciplines and the various institutions of HSCI can better pursue the promise of stem cell science and regenerative medicine.

Under the terms of the agreement, CDI will collaborate with HSCIs iPS Core Facility by providing iPSC technology support to the stem cell community. In addition, CDI will offer critical iPSC technology elements which may accelerate iPSC based science, technology and applications.

About Cellular Dynamics International:

Cellular Dynamics International (CDI), a FUJIFILM company, is a leading developer and supplier of human cells used in drug discovery, toxicity testing, and regenerative medicine applications. Leveraging technology that can be used to create induced pluripotent stem cells (iPSCs) and differentiated tissue-specific cells from any individual, CDI is committed to advancing life science research and transforming the therapeutic development process in order to fundamentally improve human health. The companys inventoried iCell products and donor-specific MyCell Products are available in the quantity, quality, purity, and reproducibility required for drug and cell therapy development. For more information please visitwww.cellulardynamics.com.

About Fujifilm

FUJIFILM Holdings Corporation, Tokyo, Japan brings continuous innovation and leading-edge products to a broad spectrum of industries, including: healthcare, with medical systems, pharmaceuticals and cosmetics; graphic systems; highly functional materials, such as flat panel display materials; optical devices, such as broadcast and cinema lenses; digital imaging; and document products. These are based on a vast portfolio of chemical, mechanical, optical, electronic, software and production technologies. In the year ended March 31, 2016, the company had global revenues of $22.1 billion, at an exchange rate of 112.54 yen to the dollar. Fujifilm is committed to environmental stewardship and good corporate citizenship. For more information, please visit:www.fujifilmholdings.com.

All product and company names herein may be trademarks of their registered owners.

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Cellular Dynamics International Signs Collaboration Agreement with Harvard Stem Cell Institute - Business Wire (press release)

IPS Cell Therapy Comments Off on Cellular Dynamics International Signs Collaboration Agreement with Harvard Stem Cell Institute – Business Wire (press release) | April 20th, 2017