"Muscle fiber" and "Myofiber" redirect here. For protein structures inside cells, see Myofibril.

A myocyte (also known as a muscle cell)[1] is the type of cell found in muscle tissue. Myocytes are long, tubular cells that develop from myoblasts to form muscles in a process known as myogenesis.[2] There are various specialized forms of myocytes: cardiac, skeletal, and smooth muscle cells, with various properties. The striated cells of cardiac and skeletal muscles are referred to as muscle fibers.[3] Cardiomyocytes are the muscle fibres that form the chambers of the heart, and have a single central nucleus.[4] Skeletal muscle fibers help support and move the body and tend to have peripheral nuclei.[5][6] Smooth muscle cells control involuntary movements such as the peristalsis contractions in the oesophagus and stomach.

The unusual microstructure of muscle cells has led cell biologists to create specialized terminology. However, each term specific to muscle cells has a counterpart that is used in the terminology applied to other types of cells:

The sarcoplasm is the cytoplasm of a muscle fiber. Most of the sarcoplasm is filled with myofibrils, which are long protein cords composed of myofilaments. The sarcoplasm is also composed of glycogen, a polysaccharide of glucose monomers, which provides energy to the cell with heightened exercise, and myoglobin, the red pigment that stores oxygen until needed for muscular activity.[7]

There are three types of myofilaments:[7]

Together, these myofilaments work to produce a muscle contraction.

The sarcoplasmic reticulum, a specialized type of smooth endoplasmic reticulum, forms a network around each myofibril of the muscle fiber. This network is composed of groupings of two dilated end-sacs called terminal cisternae, and a single transverse tubule, or T tubule, which bores through the cell and emerge on the other side; together these three components form the triads that exist within the network of the sarcoplasmic reticulum, in which each T tubule has two terminal cisternae on each side of it. The sarcoplasmic reticulum serves as reservoir for calcium ions, so when an action potential spreads over the T tubule, it signals the sarcoplasmic reticulum to release calcium ions from the gated membrane channels to stimulate a muscle contraction.[7][8]

The sarcolemma is the cell membrane of a striated muscle fiber and receives and conducts stimuli. At the end of each muscle fiber, the outer layer of the sarcolemma combines with tendon fibers.[9] Within the muscle fiber pressed against the sarcolemma are multiple flattened nuclei; this multinuclear condition results from multiple myoblasts fusing to produce each muscle fiber, where each myoblast contributes one nucleus.[7]

The cell membrane of a myocyte has several specialized regions, which may include the intercalated disk and the transverse tubular system. The cell membrane is covered by a lamina coat which is approximately 50nm wide. The laminar coat is separable into two layers; the lamina densa and lamina lucida. In between these two layers can be several different types of ions, including calcium.[10]

The cell membrane is anchored to the cell's cytoskeleton by anchor fibers that are approximately 10nm wide. These are generally located at the Z lines so that they form grooves and transverse tubules emanate. In cardiac myocytes this forms a scalloped surface.[10]

The cytoskeleton is what the rest of the cell builds off of and has two primary purposes; the first is to stabilize the topography of the intracellular components and the second is to help control the size and shape of the cell. While the first function is important for biochemical processes, the latter is crucial in defining the surface to volume ratio of the cell. This heavily influences the potential electrical properties of excitable cells. Additionally deviation from the standard shape and size of the cell can have negative prognostic impact.[10]

Each muscle fiber contains myofibrils, which are very long chains of sarcomeres, the contractile units of the cell. A cell from the biceps brachii muscle may contain 100,000 sarcomeres.[11][verification needed] The myofibrils of smooth muscle cells are not arranged into sarcomeres. The sarcomeres are composed of thin and thick filaments. Thin filaments are made of actin and attach at Z lines which help them line up correctly with each other.[12] Troponins are found at intervals along the thin filaments. Thick filaments are made of the elongated protein myosin.[13] The sarcomere does not contain organelles or a nucleus. Sarcomeres are marked by Z lines which show the beginning and the end of a sarcomere. Individual myocytes are surrounded by endomysium.

Myocytes are bound together by perimysium into bundles called fascicles; the bundles are then grouped together to form muscle tissue, which is enclosed in a sheath of epimysium. The perimysium contains blood vessels and nerves which provide for the muscle fibers. Muscle spindles are distributed throughout the muscles and provide sensory feedback information to the central nervous system. Myosin is shaped like a long shaft with a rounded end pointed out towards the surface. This structure forms the cross bridge that connects with the thin filaments.[13]

A myoblast is a type of embryonic progenitor cell that differentiates to give rise to muscle cells.[14] Differentiation is regulated by myogenic regulatory factors, including MyoD, Myf5, myogenin, and MRF4.[15] GATA4 and GATA6 also play a role in myocyte differentiation.[16]

Skeletal muscle fibers are made when myoblasts fuse together; muscle fibers therefore are cells with multiple nuclei, known as myonuclei, with each cell nucleus originating from a single myoblast. The fusion of myoblasts is specific to skeletal muscle (e.g., biceps brachii) and not cardiac muscle or smooth muscle.

Myoblasts in skeletal muscle that do not form muscle fibers dedifferentiate back into myosatellite cells. These satellite cells remain adjacent to a skeletal muscle fiber, situated between the sarcolemma and the basement membrane[17] of the endomysium (the connective tissue investment that divides the muscle fascicles into individual fibers). To re-activate myogenesis, the satellite cells must be stimulated to differentiate into new fibers.

Myoblasts and their derivatives, including satellite cells, can now be generated in vitro through directed differentiation of pluripotent stem cells.[18]

Kindlin-2 plays a role in developmental elongation during myogenesis.[19]

Muscle fibers grow when exercised and shrink when not in use. This is due to the fact that exercise stimulates the increase in myofibrils which increase the overall size of muscle cells. Well exercised muscles can not only add more size but can also develop more mitochondria, myoglobin, glycogen and a higher density of capillaries. However muscle cells cannot divide to produce new cells, and as a result we have fewer muscle cells as an adult than a newborn.[20]

When contracting, thin and thick filaments slide with respect to each other by using adenosine triphosphate. This pulls the Z discs closer together in a process called sliding filament mechanism. The contraction of all the sarcomeres results in the contraction of the whole muscle fiber. This contraction of the myocyte is triggered by the action potential over the cell membrane of the myocyte. The action potential uses transverse tubules to get from the surface to the interior of the myocyte, which is continuous within the cell membrane. Sarcoplasmic reticula are membranous bags that transverse tubules touch but remain separate from. These wrap themselves around each sarcomere and are filled with Ca2+.[13]

Excitation of a myocyte causes depolarization at its synapses, the neuromuscular junctions, which triggers action potential. With a singular neuromuscular junction, each muscle fiber receives input from just one somatic efferent neuron. Action potential in a somatic efferent neuron causes the release of the neurotransmitter acetylcholine.[21]

When the acetylcholine is released it diffuses across the synapse and binds to a receptor on the sarcolemma, a term unique to muscle cells that refers to the cell membrane. This initiates an impulse that travels across the sarcolemma.[20]

When the action potential reaches the sarcoplasmic reticulum it triggers the release of Ca2+ from the Ca2+ channels. The Ca2+ flows from the sarcoplasmic reticulum into the sarcomere with both of its filaments. This causes the filaments to start sliding and the sarcomeres to become shorter. This requires a large amount of ATP, as it is used in both the attachment and release of every myosin head. Very quickly Ca2+ is actively transported back into the sarcoplasmic reticulum, which blocks the interaction between the thin and thick filament. This in turn causes the muscle cell to relax.[20]

There are four main different types of muscle contraction: twitch, treppe, tetanus and isometric/isotonic. Twitch contraction is the process previously described, in which a single stimulus signals for a single contraction. In twitch contraction the length of the contraction may vary depending on the size of the muscle cell. During treppe (or summation) contraction muscles do not start at maximum efficiency; instead they achieve increased strength of contraction due to repeated stimuli. Tetanus involves a sustained contraction of muscles due to a series of rapid stimuli, which can continue until the muscles fatigue. Isometric contractions are skeletal muscle contractions that do not cause movement of the muscle. However, isotonic contractions are skeletal muscle contractions that do cause movement.[20]

Specialized cardiomyocytes located in the sinoatrial node are responsible for generating the electrical impulses that control the heart rate. These electrical impulses coordinate contraction throughout the remaining heart muscle via the electrical conduction system of the heart. Sinoatrial node activity is modulated, in turn, by nerve fibres of both the sympathetic and parasympathetic nervous systems. These systems act to increase and decrease, respectively, the rate of production of electrical impulses by the sinoatrial node.

There are numerous methods employed for fiber-typing, and confusion between the methods is common among non-experts. Two commonly confused methods are histochemical staining for myosin ATPase activity and immunohistochemical staining for Myosin heavy chain (MHC) type. Myosin ATPase activity is commonlyand correctlyreferred to as simply "fiber type", and results from the direct assaying of ATPase activity under various conditions (e.g. pH).[22] Myosin heavy chain staining is most accurately referred to as "MHC fiber type", e.g. "MHC IIa fibers", and results from determination of different MHC isoforms.[22] These methods are closely related physiologically, as the MHC type is the primary determinant of ATPase activity. Note, however, that neither of these typing methods is directly metabolic in nature; they do not directly address oxidative or glycolytic capacity of the fiber. When "type I" or "type II" fibers are referred to generically, this most accurately refers to the sum of numerical fiber types (I vs. II) as assessed by myosin ATPase activity staining (e.g. "type II" fibers refers to type IIA + type IIAX + type IIXA... etc.).

Below is a table showing the relationship between these two methods, limited to fiber types found in humans. Note the sub-type capitalization used in fiber typing vs. MHC typing, and that some ATPase types actually contain multiple MHC types. Also, a subtype B or b is not expressed in humans by either method.[23] Early researchers believed humans to express a MHC IIb, which led to the ATPase classification of IIB. However, later research showed that the human MHC IIb was in fact IIx,[23] indicating that the IIB is better named IIX. IIb is expressed in other mammals, so is still accurately seen (along with IIB) in the literature. Non human fiber types include true IIb fibers, IIc, IId, etc.

Further fiber typing methods are less formally delineated, and exist on more of a spectrum. They tend to be focused more on metabolic and functional capacities (i.e., oxidative vs. glycolytic, fast vs. slow contraction time). As noted above, fiber typing by ATPase or MHC does not directly measure or dictate these parameters. However, many of the various methods are mechanistically linked, while others are correlated in vivo.[26][27] For instance, ATPase fiber type is related to contraction speed, because high ATPase activity allows faster crossbridge cycling.[22] While ATPase activity is only one component of contraction speed, type I fibers are "slow", in part, because they have low speeds of ATPase activity in comparison to type II fibers. However, measuring contraction speed is not the same as ATPase fiber typing.

Because of these types of relationships, Type I and Type II fibers have relatively distinct metabolic, contractile, and motor-unit properties. The table below differentiates these types of properties. These types of propertieswhile they are partly dependent on the properties of individual fiberstend to be relevant and measured at the level of the motor unit, rather than individual fiber.[22]

Traditionally, fibers were categorized depending on their varying color, which is a reflection of myoglobin content. Type I fibers appear red due to the high levels of myoglobin. Red muscle fibers tend to have more mitochondria and greater local capillary density. These fibers are more suited for endurance and are slow to fatigue because they use oxidative metabolism to generate ATP (adenosine triphosphate). Less oxidative type II fibers are white due to relatively low myoglobin and a reliance on glycolytic enzymes.

Fibers can also be classified on their twitch capabilities, into fast and slow twitch. These traits largely, but not completely, overlap the classifications based on color, ATPase, or MHC.

Some authors define a fast twitch fiber as one in which the myosin can split ATP very quickly. These mainly include the ATPase type II and MHC type II fibers. However, fast twitch fibers also demonstrate a higher capability for electrochemical transmission of action potentials and a rapid level of calcium release and uptake by the sarcoplasmic reticulum. The fast twitch fibers rely on a well-developed, short term, glycolytic system for energy transfer and can contract and develop tension at 23 times the rate of slow twitch fibers. Fast twitch muscles are much better at generating short bursts of strength or speed than slow muscles, and so fatigue more quickly.[28]

The slow twitch fibers generate energy for ATP re-synthesis by means of a long term system of aerobic energy transfer. These mainly include the ATPase type I and MHC type I fibers. They tend to have a low activity level of ATPase, a slower speed of contraction with a less well developed glycolytic capacity. They contain high mitochondrial volumes, and the high levels of myoglobin that give them a red pigmentation. They have been demonstrated to have high concentrations of mitochondrial enzymes, thus they are fatigue resistant. Slow twitch muscles fire more slowly than fast twitch fibers, but are able to contract for a longer time before fatiguing.[28]

Individual muscles tend to be a mixture of various fiber types, but their proportions vary depending on the actions of that muscle and the species. For instance, in humans, the quadriceps muscles contain ~52% type I fibers, while the soleus is ~80% type I.[29] The orbicularis oculi muscle of the eye is only ~15% type I.[29] Motor units within the muscle, however, have minimal variation between the fibers of that unit. It is this fact that makes the size principal of motor unit recruitment viable.

The total number of skeletal muscle fibers has traditionally been thought not to change.It is believed there are no sex or age differences in fiber distribution; however, proportions of fiber types vary considerably from muscle to muscle and person to person.Sedentary men and women (as well as young children) have 45% type II and 55% type I fibers.[citation needed]People at the higher end of any sport tend to demonstrate patterns of fiber distribution e.g. endurance athletes show a higher level of type I fibers.Sprint athletes, on the other hand, require large numbers of type IIX fibers.Middle distance event athletes show approximately equal distribution of the two types. This is also often the case for power athletes such as throwers and jumpers.It has been suggested that various types of exercise can induce changes in the fibers of a skeletal muscle.[30]It is thought that if you perform endurance type events for a sustained period of time, some of the type IIX fibers transform into type IIA fibers. However, there is no consensus on the subject.It may well be that the type IIX fibers show enhancements of the oxidative capacity after high intensity endurance training which brings them to a level at which they are able to perform oxidative metabolism as effectively as slow twitch fibers of untrained subjects. This would be brought about by an increase in mitochondrial size and number and the associated related changes, not a change in fiber type.

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Myocyte - Wikipedia

Cardiac Stem Cells Comments Off on Myocyte – Wikipedia | July 31st, 2018

1. Cellular Dynamics International, Owned by FujiFilm Holdings

Founded in 2004 and listed on NASDAQ in July 2013, Cellular Dynamics International (CDI) is headquartered in Madison, Wisconsin. The company is known for its extremely robust patent portfolio containing more than 900 patents.

According to the company, CDI is the worlds largest producer of fully functional human cells derived from induced pluripotent stem (iPS) cells.[1] Their trademarked, iCell Cardiomyocytes, derived from iPSCs, are human cardiac cells used to aid drug discovery, improve the predictability of a drugs worth, and screen for toxicity. In addition, CDI provides: iCell Endothelial Cells for use in vascular-targeted drug discovery and tissue regeneration, iCell Hepatocytes, and iCell Neurons for pre-clinical drug discovery, toxicity testing, disease prediction, and cellular research.[2]

Induced pluripotent stem cells were first produced in 2006 from mouse cells and in 2007 from human cells, by Shinya Yamanaka at Kyoto University,[3] who also won the Nobel Prize in Medicine or Physiology for his work on iPSCs.[4] Yamanaka has ties to Cellular Dynamics International as a member of the scientific advisory board of iPS Academia Japan. IPS Academia Japan was originally established to manage the patents and technology of Yamanakas work, and is now the distributor of several of Cellular Dynamics products, including iCell Neurons, iCell Cardiomyocytes, and iCell Endothelial Cells.[5]

Importantly, in 2010 Cellular Dynamics became the first foreign company to be granted rights to use Yamanakas iPSC patent portfolio. Not only has CDI licensed rights to Yamanakas patents, but it also has a license to use Otsu, Japan-based Takara Bios RetroNectin product, which it uses as a tool to produce its iCell and MyCell products.[6]

Furthermore, in February 2015, Cellular Dynamics International announced it would be manufacturing cGMP HLA Superdonor stem cell lines that will support cellular therapy applications through genetic matching.[8] Currently, CDI has two HLA super donor cell lines that provide a partial HLA match to approximately 19% of the population within the U.S., and it aims to expand its master stem cell bank by collecting more donor cell lines that will cover 95% of the U.S. population.[9] The HLA super donor cell lines were manufactured using blood samples and used to produce pluripotent iPSC lines, giving the cells the capacity to differentiate into nearly any cell within the human body.

On March 30, 2015, Fujifilm Holdings Corporation announced that it was acquiring CDI for $307 million, allowing CDI to continue to run its operations in Madison, Wisconsin, and Novato, California as a consolidated subsidiary of Fujifilm.[14] A key benefit of the merger is that CDIs technology platform enables the production of high-quality fully functioning iPSCs (and other human cells) on an industrial scale, while Fujifilm has developed highly-biocompatible recombinant peptides that can be shaped into a variety of forms for use as a cellular scaffold in regenerative medicine when used in conjunction with CDIs products.[15]

Additionally, Fujifilm has been strengthening its presence in the regenerative medicine field over the past several years, including a recent A$4M equity stake in Cynata Therapeutics and an acquisition of Japan Tissue Engineering Co. Ltd. in December 2014. Most commonly called J-TEC, Japan Tissue Engineering Co. Ltd. successfully launched the first two regenerative medicine products in the country of Japan. According to Kaz Hirao, CEO of CDI, It is very important for CDI to get into the area of therapeutic products, and we can accelerate this by aligning it with strategic and technical resources present within J-TEC.

Kaz Hirao also states, For our Therapeutic businesses, we will aim to file investigational new drugs (INDs) with the U.S. FDA for the off-the-shelf iPSC-derived allogeneic therapeutic products. Currently, we are focusing on retinal diseases, heart disorders, Parkinsons disease, and cancers. For those four indicated areas, we would like to file several INDs within the next five years.

Finally, in September 2015, CDI again strengthened its iPS cell therapy capacity by setting up a new venture, Opsis Therapeutics. Opsis is focused on discovering and developing novel medicines to treat retinal diseases and is a partnership with Dr. David Gamm, the pioneer of iPS cell-derived retinal differentiation and transplantation.

In summary, several key events indicate CDIs commitment to developing iPS cell therapeutics, including:

Australian stem cell company Cynata Therapeutics (ASX:CYP) is taking a unique approach by creating allogeneic iPSC derived mesenchyal stem cell (MSCs) on a commercial scale. Cynatas Cymerus technology utilizes iPSCs provided by Cellular Dynamics International, a Fujifilm company, as the starting material for generating mesenchymoangioblasts (MCAs), and subsequently, for manufacturing clinical-grade MSCs. According to Cynatas Executive Chairman Stewart Washer who was interviewed by The Life Sciences Report, The Cymerus technology gets around the loss of potency with the unlimited iPS cellor induced pluripotent stem cellwhich is basically immortal.

On January 19, 2017, Fujifilm took an A$3.97 million (10%) strategic equity stake in Cynata, positioning the parties to collaborate on the further development and commercialization of Cynatas lead Cymerus therapeutic MSC product CYP-001 for graft-versus-host disease (GvHD). (CYP-001 is the product designation unique to the GVHD indication). The Fujifilm partnership also includes potential future upfront and milestone payments in excess of A$60 million and double-digit royalties on CYP-001 product net sales for Cynata Therapeutics, as well as a strategic relationship for the potential future manufacture of CYP-001 and certain rights to other Cynata technology.

One of the key inventors of Cynatas technology is Igor Slukvin, MD, Ph.D., Scientific Founder of Cellular Dynamics International (CDI) and Cynata Therapeutics. Dr. Slukvin has released more than 70 publications about stem cell topics, including the landmark article in Cell describing the now patented Cymerus technique. Dr. Slukvins co-inventor is Dr. James Thomson, the first person to isolate an embryonic stem cell (ESC) and one of the first people to create a human induced pluripotent stem cell (hiPSC). Dr. James Thompson was the Founder of CDI in 2004.

There are three strategic connections between Cellular Dynamics International (CDI) and Cynata Therapeutics, which include:

Recently, Cynata received advice from the UK Medicines and Healthcare products Regulatory Agency (MHRA) that its Phase I clinical trial application has been approved, titled An Open-Label Phase 1 Study to Investigate the Safety and Efficacy of CYP-001 for the Treatment of Adults With Steroid-Resistant Acute Graft Versus Host Disease. It will be the worlds first clinical trial involving a therapeutic product derived from allogeneic (unrelated to the patient) induced pluripotent stem cells (iPSCs).

Participants for Cynatas upcoming Phase I clinical trial will be adults who have undergone an allogeneic haematopoietic stem cell transplant (HSCT) to treat a hematological disorder and subsequently been diagnosed with steroid-resistant Grade II-IV GvHD. The primary objective of the trial is to assess safety and tolerability, while the secondary objective is to evaluate the efficacy of two infusions of CYP-001 in adults with steroid-resistant GvHD.

Using Professor Yamanakas Nobel Prize-winning achievement of ethically uncontentious iPSCs and CDIs high-quality iPSCs as source material, Cynata has achieved two world firsts:

Cynata has also released promising pre-clinical data in Asthma, Myocardial Infarction (Heart Attack), and Critical Limb Ischemia.

There are four key advantages of Cynatas proprietary Cymerus MSC manufacturing platform. Because the proprietary Cymerus technology allows nearly unlimited production of MSCs from a single iPSC donor, there is batch-to-batch uniformity. Utilizing a consistent starting material allows for a standardized cell manufacturing process and a consistent cell therapy product. Unlike other companies involved with MSC manufacturing, Cynata does not require a constant stream of new donors in order to source fresh stem cells for its cell manufacturing process, nor does it require the massive expansion of MSCs necessitated by reliance on freshly isolated donations.

Finally, Cynata has achieved a cost-savings advantage through its unique approach to MSC manufacturing. Its proprietary Cymerus technology addresses a critical shortcoming in existing methods of production of MSCs for therapeutic use, which is the ability to achieve economic manufacture at commercial scale.

On June 22, 2016, RIKEN announced that it is resuming its retinal induced pluripotent stem cell (iPSC) study in partnership with Kyoto University.

2013 was the first time in which clinical research involving transplant of iPSCs into humans was initiated, led by Masayo Takahashi of the RIKEN Center for Developmental Biology (CDB) in Kobe, Japan. Dr. Takahashi and her team were investigating the safety of iPSC-derived cell sheets in patients with wet-type age-related macular degeneration. Although the trial was initiated in 2013 and production of iPSCs from patients began at that time, it was not until August of 2014 that the first patient, a Japanese woman, was implanted with retinal tissue generated using iPSCs derived from her own skin cells.

A team of three eye specialists, led by Yasuo Kurimoto of the Kobe City Medical Center General Hospital, implanted a 1.3 by 3.0mm sheet of iPSC-derived retinal pigment epithelium cells into the patients retina.[196] Unfortunately, the study was suspended in 2015 due to safety concerns. As the lab prepared to treat the second trial participant, Yamanakas team identified two small genetic changes in the patients iPSCs and the retinal pigment epithelium (RPE) cells derived from them. Therefore, it is major news that the RIKEN Institute will now be resuming the worlds first clinical study involving the use of iPSC-derived cells in humans.

According to the Japan Times, this attempt at the clinical study will involve allogeneic rather than autologous iPSC-derived cells for purposes of cost and time efficiency. Specifically, the researchers will be developing retinal tissues from iPS cells supplied by Kyoto Universitys Center for iPS Cell Research and Application, an institution headed by Nobel prize winner Shinya Yamanaka. To learn about this announcement, view this article from Asahi Shimbun, a Tokyo- based newspaper.

In November 2015 Astellas Pharma announced it was acquiring Ocata Therapeutics for $379M. Ocata Therapeutics is a biotechnology company that specializes in the development of cellular therapies, using both adult and human embryonic stem cells to develop patient-specific therapies. The companys main laboratory and GMP facility are in Marlborough, Massachusetts, and its corporate offices are in Santa Monica, California.

When a number of private companies began to explore the possibility of using artificially re-manufactured iPSCs for therapeutic purposes, one such company that was ready to capitalize on the breakthrough technology was Ocata Therapeutics, at the time called Advanced Cell Technology. In 2010, the company announced that it had discovered several problematic issues while conducting experiments for the purpose of applying for U.S. Food and Drug Administration approval to use iPSCs in therapeutic applications. Concerns such as premature cell death, mutation into cancer cells, and low proliferation rates were some of the problems that surfaced. [17]

As a result, the company shifted its induced pluripotent stem cell approach to producing iPS cell-derived human platelets, as one of the benefits of a platelet-based product is that platelets do not contain nuclei, and therefore, cannot divide or carry genetic information. While the companys Induced Pluripotent Stem Cell-Derived Human Platelet Program received a great deal of media coverage in late 2012, including being awarded the December 2012 honor of being named one of the 10 Ideas that Will Shape the Year by New Scientist Magazine,[178]. Unfortunately, the company did not succeed in moving the concept through to clinical testing in 2013.

Nonetheless, Astellas is clearly continuing to develop Ocatas pluripotent stem cell technologies involving embryonic stem cells (ESCs) and induced pluripotent stem cells (iPS cells). In a November 2015 presentation by Astellas President and CEO, Yoshihiko Hatanaka, he indicated that the company will aim to develop an Ophthalmic Disease Cell Therapy Franchise based around its embryonic stem cell (ESC) and induced pluripotent stem cell (iPS cell) technology. [19]

What other companies are developing iPSC derived therapeutics and products? Share your thoughts in the comments below.

BioInformant is the first and only market research firm to specialize in the stem cell industry. BioInformant research has been cited by major news outlets that include the Wall Street Journal, Nature Biotechnology, Xconomy, and Vogue Magazine. Serving Fortune 500 leaders that include GE Healthcare, Pfizer, and Goldman Sachs. BioInformant is your global leader in stem cell industry data.

Footnotes[1] CellularDynamics.com (2014). About CDI. Available at: http://www.cellulardynamics.com/about/index.html. Web. 1 Apr. 2015.[2] Ibid.[3] Takahashi K, Yamanaka S (August 2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126 (4): 66376.[4] 2012 Nobel Prize in Physiology or Medicine Press Release. Nobelprize.org. Nobel Media AB 2013. Web. 7 Feb 2014. Available at: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/press.html. Web. 1 Apr. 2015.[5] Striklin, D (Jan 13, 2014). Three Companies Banking on Regenerative Medicine. Wall Street Cheat Sheet. Retrieved Feb 1, 2014 from, http://wallstcheatsheet.com/stocks/3-companies-banking-on-regenerative-medicine.html/?a=viewall.%5B6%5D Striklin, D (2014). Three Companies Banking on Regenerative Medicine. Wall Street Cheat Sheet [Online]. Available at: http://wallstcheatsheet.com/stocks/3-companies-banking-on-regenerative-medicine.html/?a=viewall. Web. 1 Apr. 2015.[7] Cellular Dynamics International (July 30, 2013). Cellular Dynamics International Announces Closing of Initial Public Offering [Press Release]. Retrieved from http://www.cellulardynamics.com/news/pr/2013_07_30.html.%5B8%5D Investors.cellulardynamics.com,. Cellular Dynamics Manufactures Cgmp HLA Superdonor Stem Cell Lines To Enable Cell Therapy With Genetic Matching (NASDAQ:ICEL). N.p., 2015. Web. 7 Mar. 2015.[9] Ibid.[10] Cellulardynamics.com,. Cellular Dynamics | Mycell Products. N.p., 2015. Web. 7 Mar. 2015.[11]Sirenko, O. et al. Multiparameter In Vitro Assessment Of Compound Effects On Cardiomyocyte Physiology Using Ipsc Cells.Journal of Biomolecular Screening 18.1 (2012): 39-53. Web. 7 Mar. 2015.[12] Sciencedirect.com,. Prevention Of -Amyloid Induced Toxicity In Human Ips Cell-Derived Neurons By Inhibition Of Cyclin-Dependent Kinases And Associated Cell Cycle Events. N.p., 2015. Web. 7 Mar. 2015.[13] Sciencedirect.com,. HER2-Targeted Liposomal Doxorubicin Displays Enhanced Anti-Tumorigenic Effects Without Associated Cardiotoxicity. N.p., 2015. Web. 7 Mar. 2015.[14] Cellular Dynamics International, Inc. Fujifilm Holdings To Acquire Cellular Dynamics International, Inc.. GlobeNewswire News Room. N.p., 2015. Web. 7 Apr. 2015.[15] Ibid.[16] Cyranoski, David. Japanese Woman Is First Recipient Of Next-Generation Stem Cells. Nature (2014): n. pag. Web. 6 Mar. 2015.[17] Advanced Cell Technologies (Feb 11, 2011). Advanced Cell and Colleagues Report Therapeutic Cells Derived From iPS Cells Display Early Aging [Press Release]. Available at: http://www.advancedcell.com/news-and-media/press-releases/advanced-cell-and-colleagues-report-therapeutic-cells-derived-from-ips-cells-display-early-aging/.%5B18%5D Advanced Cell Technology (Dec 20, 2012). New Scientist Magazine Selects ACTs Induced Pluripotent Stem (iPS) Cell-Derived Human Platelet Program As One of 10 Ideas That Will Shape The Year [Press Release]. Available at: http://articles.latimes.com/2009/mar/06/science/sci-stemcell6. Web. 9 Apr. 2015.[19] Astellas Pharma (2015). Acquisition of Ocata Therapeutics New Step Forward in Ophthalmology with Cell Therapy Approach. Available at: https://www.astellas.com/en/corporate/news/pdf/151110_2_Eg.pdf. Web. 29 Jan. 2017.

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Market Players Developing iPS Cell Therapies - BioInformant

IPS Cell Therapy Comments Off on Market Players Developing iPS Cell Therapies – BioInformant | July 27th, 2018

The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats' fur fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

"It's extremely exciting," said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing "the systemic rejuvenating effects," he said, "it's kind of like an unexpected fountain of youth."

"We've been studying new forms of cell therapy for the heart for some 12 years now," Marbn said.

Some of this research has focused on cardiosphere-derived cells.

"They're progenitor cells from the heart itself," Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem "that's very typical of what we find in older human beings: The heart's stiff, and it doesn't relax right, and it causes fluid to back up some," Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats -- that's elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

"The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because I'm kind of losing my hair) the animals ... regrew their fur a lot better after they'd gotten cells" compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

Why did it work?

The working hypothesis is that the cells secrete exosomes, tiny vesicles that "contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue," Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said he's begun to explore delivering the cardiac stem cells intravenously in a simple infusion -- instead of injecting them directly into the heart, which would be a complex procedure for a human patient -- and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is "very comprehensive."

"Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems," said Gerstenblith, who did not contribute to the new research. "The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly."

Todd Herron, director of the University of Michigan Frankel Cardiovascular Center's Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has "led the field in this area."

"The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon they've seen in the past," said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells "from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue," Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

"We need to make sure there's no harm being done," Herron said, adding that extending the lifetime and improving quality of life amounts to "a tradeoff between the potential risk and the potential good that can be done."

Capicor hasn't announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven "completely safe" in "over 100 human patients," so it would be possible to fast-track them into the clinic, Marbn explained: "I can't tell you that there are any plans to do that, but it could easily be done from a safety viewpoint."

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Consistency

Quality Control and Testing

Product Selection & Support

HiPSC Custom Services

Human Induced Pluripotent Stem Cells (HiPSC)Top:HiPSC express pluriotency markers OCT4, Nanog, LIN28 and SSEA-4.Bottom:HiPSC differentiate into cell derivatives from the 3 embryonic layers: Neuronal marker beta III tubulin (TUJ1), Smooth Muscle Actin (SMA) and Hepatocyte Nuclear Factor 3 Beta (HNF3b).

Cutting-edge development and manufacturing provides high quality, thoroughly-characterized HiPSC cells to researchers around the world. HiPSC are generated from somatic cells, eliminating ethical considerations associated with scientific work based on embryonic stem cells. Furthermore, being donor/patient-specific, they open possibilities for a wide variety of studies in biomedical research. Donor somatic cells carry the genetic makeup of the diseased patient, hence HiPSC can be used directly to model disease on a dish.

Thus, one of the main uses of HiPSC has been in genetic disease modeling in organs and tissues, such as the brain (Alzheimers, Autism Spectrum Disorders), heart (Familial Hypertrophic, Dilated, and Arrhythmogenic Right Ventricular Cardiomyopathies), and skeletal muscle (Amyotrophic Lateral Sclerosis, Spinal Muscle Atrophy). The combination of HiPSC technology and gene editing strategies such as the CRISPR/Cas9 system creates a powerful platform in which disease-causing mutations can be created on demand and sets of isogenic cell lines (with and without mutations) serve as convenient tools for disease modeling studies.

Other applications of HiPSC and iPSC-differentiated cells include drug screening, development, efficacy and toxicity assessment. As an example, through the FDA-backed CiPA (Comprehensive in vitro Pro-Arrhythmia Assessment) initiative, HiPSC-derived cardiac muscle cells (cardiomyocytes) are poised to constitute a new standard model for the evaluation of cardiotoxicity of new drugs, which is the main reason of drug withdrawal from the market. Finally, HiPSC-differentiated cells are being used in early stage technology development for applications in regenerative medicine. Bio-printing and tissue constructs have also been considered as attractive applications for HiPSC.

Human iPSC and Derived Cells are forResearch Use Only (RUO). Not for human clinical or therapeutic use.

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We have a lot of knowledge to share with you about stem cells and their value in skin care. We thought we would start with a current review of ongoing work in human stem cell science to give you some context. In the next few days we will be getting a lot more specific about wound healing, anti-aging, and related applications.

Human Stem Cells: Introduction

Future advances in many medical fields are thought to be dependent on continued progress in stem cell research. In this section, BTF briefly looks at the future of stem cell based therapies in the treatment of traumatic injury, degenerative diseases, and other ailments, and concludes with a review of current cell based therapies (stem cell and non-stem cell) in the field of skin care.

While the possible indications for stem cell based therapies are numerous,the field of stem cell science is young and years (or decades) may pass before todays promising laboratory results translate into useful clinical treatments. Only time will tell whether successes evolve or remain frustratingly elusive. We do know that success is possible.

The first stem cell therapy was bone marrow transplantation, originally accomplished in the mid 1960s. Last year, there were more than 50,000 such transplants worldwide. In earlier years, infusion of filtered bone marrow cells was performed with stem cells comprising but a very small part of the volume. Newer techniques have made it possible to separate cellular types to enable use of much higher concentrations of stem cells.

Much progress has been made in characterizing stem cells and understanding how they function. There is much more to the story than differentiation into tissue specific cells. Recent research shows that perhaps even more important is the fact that stem cells, especially certain types of stem cells, communicate with the cells around them by producing cellular signals called cytokines, of which there are hundreds.

Cytokines trigger specific receptors on cell membranes that result in precise responses. This phenomenon is considered an essential element in the healing response of all tissues. Identifying and characterizing the large number of cytokines is an important part of stem cell research.

Not every induced response is necessarily beneficial. It is the symphony of responses that is important. How to promote helpful responses while inhibiting non-beneficial ones is a continuing focus of cellular biochemical research as well as the basis upon which drug companies spend huge resources developing drugs to either trigger or block particular cytokine receptors. Good examples in the field of dermatology are EGFR (epidermal growth factor receptor) blocking compounds for use in treating susceptible cells, most notably cancers stimulated by EGF.

Potential Treatments

Stem cell therapies hold potential to treat many conditions and diseases that affect millions of people in the U.S.

From the Laboratory to the Bedside

Going from the research laboratory to the bedside takes time. Only one month ago, the FDA granted marketing approval for the first licensed stem cell product. Derived from donated umbilical cord blood, the product contains stem cells that can restore a recipients blood cell levels and function. In the chart below, the type of cells recovered from umbilical cord blood are those designated as HSC cell. They are the exact cells responsible for the success of bone marrow transplantation.

Of particular note are the cells designated in the chart as MSC or mesenchymal stem cells. MSC cells are the focus of intense research in the treatment of a number of conditions because this type of stem cell can differentiate into a variety of cell types including bone, cartilage, muscles, nerve, and skin (fibroblast.)

Recent announcements about stem cells being used to fabricate replacement parts (bone, cartilage, heart muscle) are based on MSC research. They truly are the duct tape of the bodys repair tool box; a phrase coined because of their importance in the healing of injuries.

Research has shown MSC cells reside in a number of tissues, including the bone marrow. Through precise chemical signaling that originate from sites of injury, MSC cells have the ability to become mobile, enter the blood stream and travel through the circulation to the injury. Upon arrival, MSCs orchestrate the healing response. Local resident stem cells are also called into action, to produce more stem cells or to produce needed tissue specific cells. In large part, MSCs accomplish their tasks bio-chemically.

Secreted cytokines have been identified as themajormechanism by which MSCs perform their important reparative functions. There are hundreds of cytokines identified thus far. The healing response is an intricate and balanced process in which many cytokines participate.

Despite their inherent ability to differentiate into essentially any type of cell, embryonic stem cells are unlikely to be a major research focus in the foreseeable future. Ethical and political considerations limit the acceptability of their use. Federal regulations permit research only on existing cell lines which are few in number. It is difficult to see how this prohibition will end any time soon.

Getting Closer butNot There Yet

MSC (mesenchymal stem cell) therapies include use ofcellsanduse of MSC factors, the cytokines or chemical messengers mentioned above. Methods of administration will likely include intravenous infusion, injections into tissues or body spaces, or development of drugs that activate or block certain cytokine effects. Drugs already in development include epidermal growth factor receptor (EGFR) blockers for use in cancer treatment.

Stem Cells and Skin Health

From fetal life to death, the numbers and activity of stem cells diminish. The chart at left shows how the population of mesenchymal stem cells in the bone marrow dwindles with age.

Knowing that stem cells are important in producing differentiated daughter cells (such as fibroblasts within the dermis) and are instrumental in orchestrating the bodys response to injury, it is easy to understand how skin damage from sun exposure, gravity, smoking, trauma, toxins, even repetitive facial movement, accumulates over time.

This is one line of evidence (we will look at others) that mesenchymal stem cells (or more specifically the relative lack of same) has a lot to do with aging. Skin aging included.

Products Claiming to Activate Skin Stem Cells

The number of skin products claiming to activate human skin stem cells is large and growing. As discussed previously on BFT, a whole slew of plant derived stem cell products are being marketing, NONE of which can actually or theoretically activate anything, especially not a human stem cell.

Other products claim to have essential nutrients or antioxidants or some other magical ingredient that will suddenly make stem cells take notice and unleash their regenerative power. It is highly unlikely, except in the most extreme case of malnourishment, that any nutrient or antioxidant is deficient enough to cause a cell not to function.

These and the botanical stem cell products are marketing ploys. Human stem cells deep within the dermis will never know whether or not these substances are applied. Moisturizers and other recognized ingredients in these products can be beneficial to skin appearancebut not because a stem cell is involved.

This is worse than junk science. This is scamming.

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Skin & Human Stem Cells - BareFacedTruth.com

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Although there are key players in markets like the U.S., Australia, and the EU, Japan continues to accelerates its position as a hub for induced pluripotent stem cell (iPS cell) therapy with generous funding, acquisitions, and strategic partnerships.

Pluripotent stem cells are cells that are capable of developing into any type of cell or tissue in the human body. These cells have the capability to replicate and help in repairing damaged tissues within the body. In 2006, the Japanese scientist Shinya Yamanaka demonstrated that an ordinary cell can be turned into a pluripotent cell by genetic modification. These genetically reprogrammed cells are known as induced pluripotent cells, also called iPS cells or iPSCs.

An induced pluripotent stem cell (iPS cell) is a type of pluripotent stem cell that has the capacity to divide indefinitely and create any cell found within the three germ layers of an organism. These layers include the ectoderm (cells giving rise to the skin and nervous system), endoderm (cells forming gastrointestinal and respiratory tracts, endocrine gland, liver, and pancreas), and mesoderm (cells forming bones, cartilage, most of the circulatory system, muscles, connective tissues, and other related tissues.).

iPS cells have significant potential for therapeutic applications. For autologous applications, the cells are extracted from the patients own body, making them genetically identical to the patient and eliminating the issues associated with tissue matching and tissue rejection.

iPS cells have the potential to be used to treat a wide range of diseases, including diabetes, heart diseases, autoimmune diseases, and neural complications, such as Parkinsons disease, Alzheimers disease.

Over the past few years, Japan has accelerated its position as a hub for regenerative medicine research, largely driven by support from Prime Minister Shinzo Abe who has identified regenerative medicine and cellular therapy as key to the Japans strategy to drive economic growth.

The Prime Minister has encouraged a growing range of collaborations between private industry and academic partners through an innovative legal framework approved last fall.

He has also initiated campaigns to drive technological advances in drugs and devices by connecting private companies with public funding sources. The result has been to drive progress in both basic and applied research involving induced pluripotent stem cells (iPS cells) and related stem cell technologies.

2013 was a landmark year in Japan, because it saw the first cellular therapy involving transplant of iPS cells into humans initiated at the RIKEN Center in Kobe, Japan.[1]Led by Masayo Takahashi of theRIKEN Center for Developmental Biology (CDB).Dr. Takahashi and her team wereinvestigating the safety of iPSC-derived cell sheets in patients with wet-type age-related macular degeneration.

To speed things along, RIKEN did not seek permission for a clinical trial involving iPS cells, but instead applied for a type of pretrial clinical research allowed under Japanese regulations.The RIKEN Center is Japans largest, most comprehensive research institution, backed by both Japans Health Ministry and government.

This pretrial clinical research allowed the RIKEN research team to test the use of iPS cells for the treatment of wet-type age-related macular degeneration (AMD) on a very small scale, in only a handful of patients.Unfortunately, the study was suspended in 2015 due to safety concerns. As the lab prepared to treat the second trial participant, Yamanakas team identified two small genetic changes in the patients iPSCs and the retinal pigment epithelium (RPE) cells derived from them.

However, in June 2016 RIKEN Institute announced that it would be resuming the clinical study involving the use of iPSC-derived cellsin humans.According to theJapan Times, this second attempt at the clinical studyis using allogeneic rather than autologous iPSC-derived cells, because of the greater cost and time efficiencies.

Specifically,the researchers will be developing retinal tissues from iPS cells supplied by Kyoto Universitys Center for iPS Cell Research and Application, an institution headed by Nobel prize winner Shinya Yamanaka.

Japan has a unique affection for iPS cells, as the cells were originally discovered by the Japanese scientist, Shinya Yamanaka of Kyoto University. Mr. Yamanaka was awarded the Nobel Prize in Physiology or Medicine for 2012, an honor shared jointly with John Gurdon, for the discovery that mature cells can be reprogrammed to become pluripotent.

In addition, Japans Education Ministry said its planning to spend 110 billion yen ($1.13 billion) on induced pluripotent stem cell research during the next 10 years, and the Japanese parliament has been discussing bills that would speed the approval process and ensure the safety of such treatments.[3]

In April, Japanese parliament even passed a law calling for Japan to make regenerative medical treatments like iPSC technology available for its citizens ahead of the rest of the world.[4] If those forces were not enough, Masayo Takahashi of the RIKEN Center for Developmental Biology in Kobe, Japan, who is heading the worlds first clinical research using iPSCs in humans, was also chosen by the journal Natureas one of five scientists to watch in 2014.[5]

Clearly, Japan is the global leader in iPS cell technologies and therapies. However, progress with stem cells has not been without setbacks within Japan, including a recent scandal at the RIKEN Institute that involved falsely manipulated research findings and a hold on the first clinical trial involving transplant of an iPS cell product into humans.

Nonetheless, Japan has emerged from these troubles to become the most liberalized nation pursuing the development of iPS cell products and services.

iPS cells represent one of the most promising advances within the field of stem cell research, because of their diverse ability to differentiate into any of the approximately 200 cell types that compose the human body.

Even though there is growing evidence to support the safety of iPS cells within cell therapy applications,some people remain concerned that patients who receive implants of iPS derived cells might be at risk of cancer, as genetic manipulation is required to create the cell type.

In a world-first, Cynata Therapeutics (ASX:CYP) received approval in September 2016 to launch a clinical trial in the UK with the worlds first first formal clinical trial of an allogeneic iPSC-derived cell product, which it calls CYP-001.The study involves centers in both the UK and Australia.

In this landmark trial, the Australian regenerative medicine company is testing an iPS cell-derived mesenchymal stem cell (MSC) product for the treatment of Graft-vs-Host-Disease (GvHD).Not surprisingly, the Japanese conglomerate Fujifilm is also involved with this historic trial.

Headquartered in Tokyo, Fujifilm is one of the largest players in regenerative medicine field and has invested significantly into stem cells through their acquisition of Cellular Dynamics International (CDI). Additionally, Fujifilm has invested in Japan Tissue Engineering Co. Ltd. (J-Tec), giving it a broad base in regenerative medicine across multiple therapeutic areas.

For a young company like Cynata, having validation from an industry giant like Fujifilm is a huge boost. As stated by Cynata CEO, Dr. Ross Macdonald, The decision by Fujifilm confirms that our technology is very exciting in their eyes. It is a useful yardstick for other investors as well. Of course, the effect of the relationship with Fujifilm on our balance sheet is also important.

If Fujifilm exercises their option to license Cynatas GvHD product, then the costs of the product and commercialization will become the responsibility of Fujifilm. Cynata would also receive milestone payments from Fujifilm of approximately $60M AUS and a double-digit royalty payment.

Cynata was also the first to scale-up manufacture of an allogeneic cGMP iPS celll line. It sourced the cell line from Cellular Dynamics International (CDI) when CDI was still an independent company listed on NASDAQ. In April 2015, CDI was subsequently acquired by Fujifilm, who as mentioned, is a major shareholder in Cynata and its strategic partner for GvHD.

Although Cynata is showing promising early-stage data from its GvHD trial, methods for commercializing iPS cells are still being explored and clinical studies investigating iPS cells remain extremely low in number.

Footnotes[1] Dvorak, K. (2014).Japan Makes Advance on Stem-Cell Therapy [Online]. Available at: http://online.wsj.com/news/articles/SB10001424127887323689204578571363010820642. Web. 14 Apr. 2015.[2] Note: In the United States, some patients have been treated with retina cells derived from embryonic stem cells (ESCs) to treat macular degeneration. There was a successful patient safety test for this stem cell treatment last year that was conducted at the Jules Stein Eye Institute in Los Angeles. The ESC-derived cells used for this study were developed by Advanced Cell Technology, Inc, a company located in Marlborough, Massachusetts.[3] Dvorak, K. (2014).Japan Makes Advance on Stem-Cell Therapy [Online]. Available at: http://online.wsj.com/news/articles/SB10001424127887323689204578571363010820642. Web. 8 Apr. 2015.[4] Ibid.[5] Riken.jp. (2014).RIKEN researcher chosen as one of five scientists to watch in 2014 | RIKEN [Online]. Available at: http://www.riken.jp/en/pr/topics/2014/20140107_1/. Web. 14 Apr. 2015.

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iPSCells Represent a Superior Approach

iPS cell-derived cardiomyocyte patch demonstrates spontaneous and synchronized contractions after 4 days in culture.

One of the greatest promises of human stem cells is to transform these early-stage cells into treatments for devastating diseases. Stem cells can potentially be used to repair damaged human tissues and to bioengineer transplantable human organs using various technologies, such as 3D printing. Using stem cells derived from another person (allogeneic transplantation) or from the patient (autologous transplantation), research efforts are underway to develop new therapies for historically difficult to treat conditions. In the past, adult stem and progenitor cells were used, but the differentiation of these cell types has proven to be difficult to control. Initial clinical trials using induced pluripotent stem (iPS) cells indicate that they are far superior for cellular therapy applications because they are better suited to scientific manipulation.

CDIs iPS cell-derived iCell and MyCell products are integral to the development of a range ofcell therapyapplications. A study using iCell Cardiomyocytesas part of a cardiac patch designed to treat heart failure is now underway. This tissue-engineered implantable patch mayemerge as apotential myocardial regeneration treatment.

Another study done with iPS cell-derived cells and kidney structures has marked an important first step towards regenerating, and eventually transplanting, a functioning human organ. In this work, iCell Endothelial Cellswere used to help to recapitulatethe blood supply of a laboratory-generated kidney scaffold. This type of outcome will be crucial for circulation and nutrient distribution in any rebuilt organ.

iCell Endothelial Cells revascularize kidney tissue. (Data courtesy of Dr. Jason Wertheim, Northwestern University)

CDI and its partners are leveraging iPS cell-derived human retinal pigment epithelial (RPE) cells to develop and manufacture autologous treatments for dry age-related macular degeneration (AMD). The mature RPE cells will be derivedfrom the patients own blood cells using CDIs MyCell process. Ifapproved by the FDA, this autologous cellular therapy wouldbe one of the first of its kind in the U.S.

Learn more about the technologybehind the development of these iPScell-derived cellular therapies.

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Get your Stem Cell Treatment in India with Dheeraj Bojwani Consultants

Stem Cell treatment is an intricate process. Stem Cell transplant patients need utmost care with respect to both emotionally and physically. Dheeraj Bojwani Consultants is a prominent medical tourism company in India making world-class medical facilities from best surgeons and hospitals accessible for international patients looking for budget-friendly treatment abroad.

Mrs. Marilyn Obiora - Nigeria Stem Cell Therapy For her Daughter in India

Hi, my name is Mrs. Marilyn Obiora, and I am from Nigeria. I came to India for my daughter's Stem Cell Therapy in India. My daughter had her first stroke in 2011. She couldn't sit, talk and had lost control of her neck. We could not find suitable help for her condition and searched for treatment in India.

We sent a query to the dheerajbojwani.com and received fast reply. Within no time we were in India for my daughter's treatment. We are very pleased with the treatment offered and there has been serious improvement in her condition in just two weeks. Thanks to the Dheeraj Bojwani Consultants, my daughter is regaining proper body functions and recuperating well.

Medical science has come a long way since its practice began thousands of years ago. Scientists are finding superior and more resourceful ways to cure diseases of different organs. Stem cells are undifferentiated parent cells that can transform into specialized cell types, divide further and produce more stem cells of the same group. Stem Cell therapy is performed to prevent or treat a health condition. Stem Cell Treatment is a reproductive therapy where nourishing tissues reinstate damaged tissues for relief from incurable diseases. Stem cell treatment is one of the approaches with a potential to heal a wide range of diseases in the near future. Science has always provided ground-breaking answers to obdurate health conditions, but the latest medical miracle that the medical fraternity has gifted to mankind is the Stem Cell Therapy.

Stem cell therapy is an array of techniques intended to replace cells damaged or destroyed by disease with healthy functioning ones. Even though the techniques are relatively new, their applications and advantages are broad and surprising the medical world with every new research. Stem cells are obtained from bone marrow or human umbilical cord. They are also known as the fundamental cells of our body and have the power to develop into any type of tissue cell in the body. Stem cell treatment is based on the principle that the cells move to the site of injury and transform themselves to form new tissue cells to replace the damaged ones. They have the capacity to proliferate and renew themselves indefinitely and can form mature muscle cells, nerve cells, and blood cells. In this type of therapy, they are derived from the body, kept under artificial conditions where they mature into the type of cells that are required to heal a certain part of the body or disease.

Stem cells are being studied and used to treat different types of cancers, disorders related to the blood, immune disorders, and metabolic disorders. Some other diseases and health conditions that may be healed using stem cell treatment are,

Recently, a team of researchers successfully secured the peripheral nerves in the upper arms of a patient suffering peripheral nerve damage, by using skin-derived stem cells (SDSCs) and a previously developed collagen tube, premeditated to successfully bridge gaps in injured nerves.

A research has found potential in bone marrow stem cell therapy to treat TB. Patients injected with new mesenchymal stromal cells derived from their own bone marrow showed positive response against the TB bacteria. The therapy also didnt show any serious adverse effects.

Stem cells are also used to treat hair loss. A small amount of fat is taken from the waist area of the patient by a mini-liposuction process. This fat contains dormant stem cells, and is then spun to separate the stem cells from the fat. An activation solution is added to the cells, and may be multiplied in number, depending on the size of the bald area. Once activated, the solution is washed off so that only cells remain. Now, the stem cells are injected into the scalp. One can find some hair growth in about two to four weeks.

Damaged cones in retinas can be regenerated and eyesight restored through stem cell. Stem cell therapy could regenerate damaged cones in people, especially in the cone-rich regions of the retina that provide daytime/color vision.

Kidney transplants have become more common and easier thanks stem cell therapy. Normally patients who undergo organ transplants need a lifetime of costly anti-rejection drugs but the new procedure may negate this need, with organ donors stem cells. Unless there is a perfect match donor, patients have to wait long for an organ transplant. Though still in early stages, the stem cell research is being considered as a potential player in the field of transplantation.

Transplanted stem cells serve as migratory signals for the brain's own neurogenic cells, guiding the new host cells towards the injured brain tissue. Stem cells have the potential to give rise to many different cell types that carry out different functions. While the stem cells in adult bone marrow tend to develop into the cells that make up the organ system from which they originated. These multipotent stem cells can be manipulated to take up the characteristics of neural cells.

Experts are using Stem cell Transplant to treat the symptoms of spinal cord injury by transplantation of cells directly into the gray matter of the patients spinal cord. Expectedly, the cells will integrate into the patients own neural tissue and create new circuitry to help transmit nerve signals to muscles. The transplanted cells may also promote reorganization of the spinal cord segmental circuitry, possibly leading to improved motor function.

Stem cells are capable of differentiating into a variety of different cell types, and if the architecture of damaged tendon is restored, it would improve the management of patients with these injuries significantly.

A promising benefit of stem cell therapy is its potential for cardiac tissue regeneration to reverse tissue loss underlying the development of heart failure after cardiac injury. Possible mechanisms of recovery include generation of heart muscle cells, stimulation of new blood vessels growth, secretion of growth factors.

It is a complex and multifarious procedure, with several risks and complications involved and is thus recommended to a few patients when other treatments have failed. Stem Cell therapy is recommended when other treatments fail to give positive results. The best candidates for Stem cell Treatment are those in good health and have stem cells available from a sibling, or any other family member.

India has been recognized as the new medical destination for Stem Cell therapies. Hundreds of international patients from around the world visit to India for high quality medical care at par with developed nations like the US, UK, at the most affordable costs. The Hospitals in India have the most extensive diagnostic and imaging facilities including Asias most advanced MRI and CT technology. India provides services of the most leading doctors and Stem Cell Therapy professionals at reasonable cost budget in the following cities

India offers outstanding Stem Cell Treatment at rates far below that prevailing in USA or other Western countries. Even with travel expenses taken into account, the comprehensive medical tourism packages still provide a savings measured in the thousands of dollars for major procedures. A cost comparison can give you the exact idea about the difference:

There are many reasons for India becoming a popular medical tourism spot is the low cost stem cell treatment in the area. When in contrast to the first world countries like, US and UK, medical care in India costs as much as 60-90% lesser, that makes it a great option for the citizens of those countries to opt for stem cell treatment in India because of availability of quality healthcare in India, affordable prices strategic connectivity, food, zero language barrier and many other reasons.

The maximum number of patients for Stem Cell Treatment comes from Nigeria, Kenya, Ethiopia, USA, UK, Australia, Saudi Arabia, UAE, Uzbekistan, Bangladesh

Below are the downloadable links that will help you to plan your medical trip to India in a more organized and better way. Attached word and pdf files gives information that will help you to know India more and make your trip to India easy and memorable one.

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Editor's Note: This story, originally printed in the September 1999 issue of Scientific American, is being posted due to a new study showing that nerve cells can be regenerated by knocking out genes that typically inhibit their growth.

For Chinese gymnast Sang Lan, the cause was a highly publicized headfirst fall during warm-ups for the 1998 Goodwill Games. For Richard Castaldo of Littleton, Colo., it was bullets; for onetime football player Dennis Byrd, a 1992 collision on the field; and for a child named Samantha Jennifer Reed, a fall during infancy. Whatever the cause, the outcome of severe damage to the spinal cord is too often the same: full or partial paralysis and loss of sensation below the level of the injury.

Ten years ago doctors had no way of limiting such disability, aside from stabilizing the cord to prevent added destruction, treating infections and prescribing rehabilitative therapy to maximize any remaining capabilities. Nor could they rely on the cord to heal itself. Unlike tissue in the peripheral nervous system, that in the central nervous system (the spinal cord and brain) does not repair itself effectively. Few scientists held out hope that the situation would ever change.

Then, in 1990, a human trial involving multiple research centers revealed that a steroid called methylprednisolone could preserve some motor and sensory function if it was administered at high doses within eight hours after injury. For the first time, a therapy had been proved to reduce dysfunction caused by spinal cord trauma. The improvements were modest, but the success galvanized a search for additional therapies. Since then, many investigatorsincluding us have sought new ideas for treatment in studies of why an initial injury triggers further damage to the spinal cord and why the disrupted tissue fails to reconstruct itself.

In this article we will explain how the rapidly burgeoning knowledge might be harnessed to help people with spinal cord injuries. We should note, however, that workers have also been devising strategies that compensate for cord damage instead of repairing it. In the past two years, for example, the U.S. Food and Drug Administration has approved two electronic systems that regulate muscles by sending electrical signals through implanted wires. One returns certain hand movements (such as grasping a cup or a pen) to patients who have shoulder mobility; another restores a measure of control over the bladder and bowel.

A different approach can also provide grasping ability to certain patients. Surgeons identify tendons that link paralyzed forearm muscles to the bones of the hand, disconnect them from those muscles and connect them to arm muscles regulated by parts of the spine above the injury (and thus still under voluntary control). Further, many clinicians suspect that initiating rehabilitative therapy earlyexercising the limbs almost as soon as the spine is stabilizedmay enhance motor and sensory function in limbs. Those perceptions have not been tested rigorously in people, but animal studies lend credence to them.

The Cord at Work The organ receiving all this attention is no thicker than an inch but is the critical highway of communication between the brain and the rest of the body. The units of communication are the nerve cells (neurons), which consist of a bulbous cell body (home to the nucleus), trees of signal-detecting dendrites, and an axon that extends from the cell body and carries signals to other cells. Axons branch toward their ends and can maintain connections, or synapses, with many cells at once. Some traverse the entire length of the cord.

The soft, jellylike cord has two major systems of neurons. Of these, the descending, motor pathways control both smooth muscles of internal organs and striated muscles; they also help to modulate the actions of the autonomic nervous system, which regulates blood pressure, temperature and the bodys circulatory response to stress. The descending pathways begin with neurons in the brain, which send electrical signals to specific levels, or segments, of the cord. Neurons in those segments then convey the impulses outward beyond the cord.

The other main system of neurons the ascending, sensory pathwaystransmit sensory signals received from the extremities and organs to specific segments of the cord and then up to the brain. Those signals originate with specialized, transducer cells, such as sensors in the skin that detect changes in the environment or cells that monitor the state of internal organs. The cord also contains neuronal circuits (such as those involved in reflexes and certain aspects of walking) that can be activated by incoming sensory signals without input from the brain, although they can be influenced by messages from the brain.

The cell bodies in the trunk of the cord reside in a gray, butterfly-shaped core that spans the length of the spinal cord. The ascending and descending axonal fibers travel in a surrounding area known as the white matter, so called because the axons are wrapped in myelin, a white insulating material. Both regions also house glial cells, which help neurons to survive and work properly. The glia include star-shaped astrocytes, microglia (small cells that resemble components of the immune system) and oligodendrocytes, the myelin producers. Each oligodendrocyte myelinates as many as 40 different axons simultaneously.

The precise nature of a spinal cord injury can vary from person to person. Nevertheless, certain commonalities can be discerned.

When Injury Strikes When a fall or some other force fractures or dislocates the spinal column, the vertebral bones that normally enclose and protect the cord can crush it, mechanically killing and damaging axons. Occasionally, only the gray matter in the damaged area is significantly disrupted. If the injury ended there, muscular and sensory disturbances would be confined to tissues that send input to or receive it from neurons in the affected level of the cord, without much disturbing function below that level.

For instance, if only the gray matter were affected, a cervical 8 (C8) lesion involving the cord segment where the nerves labeled C8 originatewould paralyze the hands without impeding walking or control over the bowel and bladder. No signals would go out to, or be received from, the tissues connected to the C8 nerves, but the axons conveying signals up and down the surrounding white matter would keep working.

In contrast, if all the white matter in the same cord segment were destroyed, the injury would now interrupt the vertical signals, stopping messages that originated in the brain from traveling below the damaged area and blocking the flow to the brain of sensory signals coming from below the wound. The person would become paralyzed in the hands and lower limbs and would lose control over urination and defecation.

Sadly, the initial insult is only the beginning of the trouble. The early mechanical injury triggers a second wave of damageone that, over the subsequent minutes, hours and days, progressively enlarges the lesion and thus the extent of functional impairment. This secondary spread tends to occur longitudinally through the gray matter at first before expanding into the white matter (roughly resembling the inflation of a footballshaped balloon). Eventually the destruction can encompass several spinal segments above and below the original wound.

The end result is a complex state of disrepair. Axons that have been damaged become useless stumps, connected to nothing, and their severed terminals disintegrate. Often many axons remain intact but are rendered useless by loss of their insulating myelin. A fluid-filled cavity, or cyst, sits where neurons, other cells and axons used to be. And glial cells proliferate abnormally, creating clusters termed glial scars. Together the cyst and scars pose a formidable barrier to any cut axons that might somehow try to regrow and connect to cells they once innervated. A few axons may remain whole, myelinated and able to carry signals up or down the spine, but often their numbers are too small to convey useful directives to the brain or muscles.

First, Contain the Damage If all these changes had to be fully reversed to help patients, the prospects for new treatments would be grim. Fortunately, it appears that salvaging normal activity in as little as 10 percent of the standard axon complement would sometimes make walking possible for people who would otherwise lack that capacity. In addition, lowering the level of injury by just a single segment (about half an inch) can make an important difference to a persons quality of life. People with a C6 injury have no power over their arms, save some ability to move their shoulders and flex their elbows. But individuals with a lower, C7 injury can move the shoulders and elbow joints and extend the wrists; with training and sometimes a tendon transfer, they can make some use of their arms and hands.

Because so much damage arises after the initial injury, clarifying how that secondary destruction occurs and blocking those processes are critical. The added wreckage has been found to result from many interacting mechanisms.

Within minutes of the trauma, small hemorrhages from broken blood vessels appear, and the spinal cord swells. The blood vessel damage and swelling prevent the normal delivery of nutrients and oxygen to cells, causing many of them to starve to death.

Meanwhile damaged cells, axons and blood vessels release toxic chemicals that go to work on intact neighboring cells. One of these chemicals in particular triggers a highly disruptive process known as excitotoxicity. In the healthy cord the end tips of many axons secrete minute amounts of glutamate. When this chemical binds to receptors on target neurons, it stimulates those cells to fire impulses. But when spinal neurons, axons or astrocytes are injured, they release a flood of glutamate. The high levels overexcite neighboring neurons, inducing them to admit waves of ions that then trigger a series of destructive events in the cellsincluding production of free radicals. These highly reactive molecules can attack membranes and other components of formerly healthy neurons and kill them.

Until about a year ago, such excitotoxicity, also seen after a stroke, was thought to be lethal to neurons alone, but new results suggest it kills oligodendrocytes (the myelin producers) as well. This effect may help explain why even unsevered axons become demyelinated, and thus unable to conduct impulses, after spinal cord trauma.

Prolonged inflammation, marked by an influx of certain immune system cells, can exacerbate these effects and last for days. Normally, immune cells stay in the blood, unable to enter tissues of the central nervous system. But they can flow in readily where blood vessels are damaged. As they and microglia become activated in response to an injury, the activated cells release still more free radicals and other toxic substances.

Methylprednisolone, the first drug found to limit spinal cord damage in humans, may act in part by reducing swelling, inflammation, the release of glutamate and the accumulation of free radicals. The precise details of how it helps patients remain unclear, however.

Studies of laboratory animals with damaged spinal cords indicate that drugs able to stop cells from responding to excess glutamate could minimize destruction as well. Agents that selectively block glutamate receptors of the so-called AMPA class, a kind abundant on oligodendrocytes and neurons, seem to be particularly effective at limiting the final extent of a lesion and the related disability. Certain AMPA receptor antagonists have already been tested in early human trials as a therapy for stroke, and related compounds could enter safety studies in patients with spinal cord injury within several years.

Much of the early cell loss in the injured spinal cord occurs by necrosis, a process in which cells essentially become passive victims of murder. In the past few years, neurobiologists have also documented a more active form of cell death, somewhat akin to suicide, in the cord. Days or weeks after the initial trauma, a wave of this cell suicide, or apoptosis, frequently sweeps through oligodendrocytes as many as four segments from the trauma site. This discovery, too, has opened new doors for protective therapy. Rats given apoptosisinhibiting drugs retained more ambulatory ability after a traumatic spinal cord injury than did untreated rats.

In the past few years, biologists have identified many substances, called neurotrophic factors, that also promote neuronal and glial cell survival. A related substance, GM-1 ganglioside (Sygen), is now being evaluated for limiting cord injury in humans. Ultimately, interventions for reducing secondary damage in the spinal cord will probably enlist a variety of drugs given at different times to thwart specific mechanisms of death in distinct cell populations.

The best therapy would not only reduce the extent of an injury but also repair damage. A key component of that repair would be stimulating the regeneration of damaged axonsthat is, inducing their elongation and reconnection with appropriate target cells.

Although neurons in the central nervous system of adult mammals generally fail to regenerate damaged axons, this lapse does not stem from an intrinsic property of those cells. Rather the fault lies with shortcomings in their environment. After all, neurons elsewhere in the body and in the immature spinal cord and brain regrow axons readily, and animal experiments have shown that the right environment can induce axons of the spinal cord to extend quite far.

Then, Induce Regeneration One shortcoming of the cord environment turns out to be an overabundance of molecules that actively inhibit axonal regenerationsome of them in myelin. The scientists who discovered these myelin-related inhibitors have produced a molecule named IN-1 (inhibitorneutralizing antibody) that blocks the action of those inhibitors. They have also demonstrated that infusion of mouse-derived IN-1 into the injured rat spinal cord can lead to long-distance regrowth of some interrupted axons. And when pathways controlling front paw activity are severed, treated animals regain some paw motion, whereas untreated animals do not. The rodent antibody would be destroyed by the human immune system, but workers are developing a humanized version for testing in people.

Many other inhibitory molecules have now been found as well, including some produced by astrocytes and a number that reside in the extracellular matrix (the scaffolding between cells). Given this array, it seems likely that combination therapies will be needed to counteract or shut down the production of multiple inhibitors at once.

Beyond removing the brakes on axonal regrowth, a powerful tactic would supply substances that actively promote axonal extension. The search for such factors began with studies of nervous system development. Decades ago scientists isolated nerve growth factor (NGF), a neurotrophic factor that supports the survival and development of the peripheral nervous system. Subsequently, this factor turned out to be part of a family of proteins that both enhance neuronal survival and favor the outgrowth of axons. Many other families of neurotrophic factors with similar talents have been identified as well. For instance, the molecule neurotrophin- 3 (NT-3) selectively encourages the growth of axons that descend into the spinal cord from the brain.

Luckily, adult neurons remain able to respond to axon-regenerating signals from such factors. Obviously, however, natural production of these substances falls far short of the amount needed for spinal cord repair. Indeed, manufacture of some of the compounds apparently declines, instead of rising, for weeks after a spinal trauma occurs. According to a host of animal studies, artificially raising those levels after an injury can enhance regeneration. Some regeneration- promoting neurotrophic factors, such as basic fibroblast growth factor, have been tested in stroke patients. None has been evaluated as an aid to regeneration in people with spinal cord damage, but many are being assessed in animals as a prelude to such studies.

Those considering neurotrophic factors for therapy will have to be sure that the agents do not increase pain, a common long-term complication of spinal cord injury. This pain has many causes, but one is the sprouting of nascent axons where they do not belong (perhaps in a failed attempt to address the injury) and their inappropriate connection to other cells. The brain sometimes misinterprets impulses traveling through those axons as pain signals. Neurotrophic factors can theoretically exacerbate that problem and can also cause pain circuits in the spiral cord and pain-sensing cells in the skin to become oversensitive.

After axons start growing, they will have to be guided to their proper targets, the cells to which they were originally wired. But how? In this case, too, studies of embryonic development have offered clues.

During development, growing axons are led to their eventual targets by molecules that act on the leading tip, or growth cone. In the past five years especially, a startling number of substances that participate in this process have been uncovered. Some, such as a group called netrins, are released or displayed by neurons or glial cells. They beckon axons to grow in some directions and repel growth in others. Additional guidance molecules are fixed components of the extracellular matrix. Certain of the matrix molecules bind well to specific molecules (cell adhesion molecules) on the growth cones and thus provide anchors for growing axons. During development, the required directional molecules are presented to the growth cones in specific sequences.

Establish Proper Connections At the moment, no one knows how to supply all the needed chemical road signs in the right places. But some findings suggest that regeneration may be aided by supplying just a subset of those targeting moleculessay, a selection of netrins and components from the extracellular matrix. Substances already in the spinal cord may well be capable of supplying the rest of the needed guidance.

A different targeting approach aims to bridge the gap created by cord damage. It directs injured axons toward their proper destinations by supplying a conduit through which they can travel or by providing another friendly scaffolding able to give physical support to the fibers as they try to traverse the normally impenetrable cyst. The scaffolding can also serve as a source of growth-promoting chemicals.

For instance, researchers have implanted tubes packed with Schwann cells into the gap where part of the spinal cord was removed in rodents. Schwann cells, which are glia of the peripheral nervous system, were chosen because they have many attributes that favor axonal regeneration. In animal experiments, such grafts spurred some axonal growth into the tubes.

A second bridging material consists of olfactory-ensheathing glial cells, which are found only in the tracts leading from the nose to the olfactory bulbs of the brain. When those cells were put into the rat spinal cord where descending tracts had been cut, the implants spurred partial regrowth of the axons over the implant. Transplanting the olfactory-ensheathing glia with Schwann cells led to still more extensive growth.

In theory, a biopsy could be performed to obtain the needed olfactory ensheathing glia from a patient. But once the properties that enable them (or other cells) to be competent escorts for growing axons are determined, researchers may instead be able to genetically alter other cell types if desired, giving them the required combinations of growthpromoting properties.

Fibroblasts (cells common in connective tissue and the skin) are among those already being engineered to serve as bridges. They have been altered to produce the neurotrophic molecule NT-3 and then transplanted into the cut spinal cord of rodents. The altered fibroblasts have resulted in partial regrowth of axons. Along with encouraging axonal regrowth, NT-3 stimulates remyelination. In these studies the genetically altered fibroblasts have enhanced myelination of regenerated axons and improved hind limb activity.

Replace Lost Cells Other transplantation schemes would implant cells that normally occur in the central nervous system. In addition to serving as bridges and potentially releasing proteins helpful for axonal regeneration, certain of these grafts might be able to replace cells that have died.

Transplantation of tissue from the fetal central nervous system has produced a number of exciting results in animals treated soon after a trauma. This immature tissue can give rise to new neurons, complete with axons that travel long distances into the recipients tissues (up and down several segments in the spinal cord or out to the periphery). It can also prompt host neurons to send regenerating axons into the implanted tissue. In addition, transplant recipients, unlike untreated animals, may recover some limb function, such as the ability to move the paw in useful ways. What is more, studies of fetal tissue implants suggest that axons can at times find appropriate targets even in the absence of externally supplied guidance molecules. The transplants, however, are far more effective in the immature spinal cord than in the injured adult cordan indication that young children would probably respond to such therapy much better than adolescents or adults would.

Some patients with long-term spinal cord injuries have received human fetal tissue transplants, but too little information is available so far for drawing any conclusions. In any case, application of fetal tissue technology in humans will almost surely be limited by ethical dilemmas and a lack of donor tissue. Therefore, other ways of achieving the same results will have to be devised. Among the alternatives is transplanting stem cells: immature cells that are capable of dividing endlessly, of making exact replicas of themselves and also of spawning a range of more specialized cell types.

Various kinds of stem cells have been identified, including ones that generate all the cell types in the blood system, the skin, or the spinal cord and brain. Stem cells found in the human adult central nervous system have, moreover, been shown capable of producing neurons and all their accompanying glia, although these so-called neural stem cells seem to be quiescent in most regions of the system. In 1998 a few laboratories also obtained much more versatile stem cells from human tissue. These human embryonic stem cells (in common with embryonic stem cells obtained previously from other vertebrates) can be grown in culture and, in theory, can yield almost all the cell types in the body, including those of the spinal cord.

Stem Cell Strategies How might stem cells aid in spinal cord repair? A great deal will be possible once biologists learn how to obtain those cells readily from a patient and how to control the cells differentiation. Notably, physicians might be able to withdraw neural stem cells from a patients brain or spinal cord, expand the numbers of the still undifferentiated cells in the laboratory and place the enlarged population in the same persons cord with no fear that the immune system will reject the implant as foreign. Or they might begin with frozen human embryonic stem cells, coax those cells to become precursors, or progenitors, of spinal cells and implant a large population of the precursors. Studies proposing to examine the effects on patients with spinal cord injuries of transplanting neural stem cells (isolated from the patients brains by biopsy) are being considered.

Simply implanting progenitor cells into the cord may be enough to prod them to multiply and differentiate into the needed lineages and thus to replace useful numbers of lost neurons and glial cells and establish the proper synaptic connections between neurons. Stem cells transplanted into the normal and injured nervous systems of animals can form neurons and glia appropriate for the region of transplantation. Combined with the fetal tissue results, this outcome signifies that many important cues for differentiation and targeting preexist in the injured nervous system. But if extra help is needed, scientists might be able to deliver it through genetic engineering. As a rule, to be genetically altered easily, cells have to be able to divide. Stem cells, unlike mature neurons, fit that bill.

Scenarios involving stem cell transplants are admittedly futuristic, but one day they themselves may become unnecessary, replaced by gene therapy alone. Delivery of genes into surviving cells in the spinal cord could enable those cells to manufacture and release a steady supply of proteins able to induce stem cell proliferation, to enhance cell differentiation and survival, and to promote axonal regeneration, guidance and remyelination. For now, though, technology for delivering genes to the central nervous system and for ensuring that the genes survive and work properly is still being refined.

Until, and even after, cell transplants and gene therapies become commonplace for coping with spinal cord injury, patients might gain help through a different avenuedrugs that restore signal conduction in axons quieted by demyelination. Ongoing clinical tests are evaluating the ability of a drug called 4-aminopyridine to compensate for demyelination. This agent temporarily blocks potassium ion channels in axonal membranes and, in so doing, allows axons to transmit electrical signals past zones of demyelination. Some patients receiving the drug have demonstrated modest improvement in sensory or motor function.

At first glance, this therapy might seem like a good way to treat multiple sclerosis, which destroys the myelin around axons of neurons in the central nervous system. Patients with this disease are prone to seizures, however, and 4-aminopyridine can exacerbate that tendency.

Neurotrophic factors, such as NT-3, that can stimulate remyelination of axons in animals could be considered for therapy as well. NT-3 is already entering extensive (phase III) trials in humans with spinal cord injury, though not to restore myelin. It will be administered by injection in amounts capable of acting on nerves in the gut and of enhancing bowel function, but the doses will be too low to yield high concentrations in the central nervous system. If the drug proves to be safe in this trial, though, that success could pave the way for human tests of doses large enough to enhance myelination or regeneration.

The Years Ahead Clearly, the 1990s have seen impressive advances in understanding of spinal cord injury and the controls on neuronal growth. Like axons inching toward their targets, a growing number of investigators are pushing their way through the envelope of discovery and generating a rational game plan for treating such damage. That approach will involve delivery of multiple therapies in an orderly sequence. Some treatments will combat secondary injury, some will encourage axonal regrowth or remyelination, and some will replace lost cells.

When will the new ideas become real treatments? We wish we had an answer. Drugs that work well in animals do not always prove useful in people, and those that show promise in small human trials do not always pan out when examined more extensively. It is nonetheless encouraging that at least two human trials are now under way and that others could start in the next several years.

Limiting an injury will be easier than reversing it, and so treatments for ameliorating the secondary damage that follows acute trauma can be expected to enter human testing most quickly. Of the repair strategies, promoting remyelination will be the simplest to accomplish, because all it demands is the recoating of intact axons. Remyelination strategies have the potential to produce meaningful recovery of function, such as returning control over the bladder or bowel abilities that uninjured people take for granted but that would mean the world to those with spinal cord injuries.

Of course, tendon-transfer surgery and advanced electrical devices can already restore important functions in some patients. Yet for many people, a return of independence in daily activities will depend on reconstruction of damaged tissue through the regrowth of injured axons and the reconnection of disrupted pathways.

So far, few interventions in animals with well-established spinal cord injuries have achieved the magnitude of regrowth and synapse formation that would be needed to provide a hand grasp or the ability to stand and walk in human adults with long-term damage. Because of the great complexities and difficulties involved in those aspects of cord repair, we cannot guess when reconstructive therapies might begin to become available. But we anticipate continued progress toward that end.

Traditionally, medical care for patients with spinal cord injury has emphasized compensatory strategies that maximize use of any residual cord function. That focus is now expanding, as treatments designed to repair the damaged cord and restore lost functionscience fiction only a decade agoare becoming increasingly plausible.

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Repairing the Damaged Spinal Cord - Scientific American

Spinal Cord Stem Cells Comments Off on Repairing the Damaged Spinal Cord – Scientific American | June 21st, 2018

Charles A. Goldthwaite, Jr., Ph.D.

Cardiovascular disease (CVD), which includes hypertension, coronary heart disease (CHD), stroke, and congestive heart failure (CHF), has ranked as the number one cause of death in the United States every year since 1900 except 1918, when the nation struggled with an influenza epidemic.1 In 2002, CVD claimed roughly as many lives as cancer, chronic lower respiratory diseases, accidents, diabetes mellitus, influenza, and pneumonia combined. According to data from the 19992002 National Health and Nutrition Examination Survey (NHANES), CVD caused approximately 1.4 million deaths (38.0 percent of all deaths) in the U.S. in 2002. Nearly 2600 Americans die of CVD each day, roughly one death every 34 seconds. Moreover, within a year of diagnosis, one in five patients with CHF will die. CVD also creates a growing economic burden; the total health care cost of CVD in 2005 was estimated at $393.5 billion dollars.

Given the aging of the U.S. population and the relatively dramatic recent increases in the prevalence of cardiovascular risk factors such as obesity and type 2 diabetes,2,3 CVD will continue to be a significant health concern well into the 21st century. However, improvements in the acute treatment of heart attacks and an increasing arsenal of drugs have facilitated survival. In the U.S. alone, an estimated 7.1 million people have survived a heart attack, while 4.9 million live with CHF.1 These trends suggest an unmet need for therapies to regenerate or repair damaged cardiac tissue.

Ischemic heart failure occurs when cardiac tissue is deprived of oxygen. When the ischemic insult is severe enough to cause the loss of critical amounts of cardiac muscle cells (cardiomyocytes), this loss initiates a cascade of detrimental events, including formation of a non-contractile scar, ventricular wall thinning (see Figure 6.1), an overload of blood flow and pressure, ventricular remodeling (the overstretching of viable cardiac cells to sustain cardiac output), heart failure, and eventual death.4 Restoring damaged heart muscle tissue, through repair or regeneration, therefore represents a fundamental mechanistic strategy to treat heart failure. However, endogenous repair mechanisms, including the proliferation of cardiomyocytes under conditions of severe blood vessel stress or vessel formation and tissue generation via the migration of bone-marrow-derived stem cells to the site of damage, are in themselves insufficient to restore lost heart muscle tissue (myocardium) or cardiac function.5 Current pharmacologic interventions for heart disease, including beta-blockers, diuretics, and angiotensin-converting enzyme (ACE) inhibitors, and surgical treatment options, such as changing the shape of the left ventricle and implanting assistive devices such as pacemakers or defibrillators, do not restore function to damaged tissue. Moreover, while implantation of mechanical ventricular assist devices can provide long-term improvement in heart function, complications such as infection and blood clots remain problematic.6 Although heart transplantation offers a viable option to replace damaged myocardium in selected individuals, organ availability and transplant rejection complications limit the widespread practical use of this approach.

Figure 6.1. Normal vs. Infarcted Heart. The left ventricle has a thick muscular wall, shown in cross-section in A. After a myocardial infarction (heart attack), heart muscle cells in the left ventricle are deprived of oxygen and die (B), eventually causing the ventricular wall to become thinner (C).

2007 Terese Winslow

The difficulty in regenerating damaged myocardial tissue has led researchers to explore the application of embryonic and adult-derived stem cells for cardiac repair. A number of stem cell types, including embryonic stem (ES) cells, cardiac stem cells that naturally reside within the heart, myoblasts (muscle stem cells), adult bone marrow-derived cells, mesenchymal cells (bone marrow-derived cells that give rise to tissues such as muscle, bone, tendons, ligaments, and adipose tissue), endothelial progenitor cells (cells that give rise to the endothelium, the interior lining of blood vessels), and umbilical cord blood cells, have been investigated to varying extents as possible sources for regenerating damaged myocardium. All have been tested in mouse or rat models, and some have been tested in large animal models such as pigs. Preliminary clinical data for many of these cell types have also been gathered in selected patient populations.

However, clinical trials to date using stem cells to repair damaged cardiac tissue vary in terms of the condition being treated, the method of cell delivery, and the primary outcome measured by the study, thus hampering direct comparisons between trials.7 Some patients who have received stem cells for myocardial repair have reduced cardiac blood flow (myocardial ischemia), while others have more pronounced congestive heart failure and still others are recovering from heart attacks. In some cases, the patient's underlying condition influences the way that the stem cells are delivered to his/her heart (see the section, quot;Methods of Cell Deliveryquot; for details). Even among patients undergoing comparable procedures, the clinical study design can affect the reporting of results. Some studies have focused on safety issues and adverse effects of the transplantation procedures; others have assessed improvements in ventricular function or the delivery of arterial blood. Furthermore, no published trial has directly compared two or more stem cell types, and the transplanted cells may be autologous (i.e., derived from the person on whom they are used) or allogeneic (i.e., originating from another person) in origin. Finally, most of these trials use unlabeled cells, making it difficult for investigators to follow the cells' course through the body after transplantation (see the section quot;Considerations for Using These Stem Cells in the Clinical Settingquot; at the end of this article for more details).

Despite the relative infancy of this field, initial results from the application of stem cells to restore cardiac function have been promising. This article will review the research supporting each of the aforementioned cell types as potential source materials for myocardial regeneration and will conclude with a discussion of general issues that relate to their clinical application.

In 2001, Menasche, et.al. described the successful implantation of autologous skeletal myoblasts (cells that divide to repair and/or increase the size of voluntary muscles) into the post-infarction scar of a patient with severe ischemic heart failure who was undergoing coronary artery bypass surgery.8 Following the procedure, the researchers used imaging techniques to observe the heart's muscular wall and to assess its ability to beat. When they examined patients 5 months after treatment, they concluded that treated hearts pumped blood more efficiently and seemed to demonstrate improved tissue health. This case study suggested that stem cells may represent a viable resource for treating ischemic heart failure, spawning several dozen clinical studies of stem cell therapy for cardiac repair (see Boyle, et.al.7 for a complete list) and inspiring the development of Phase I and Phase II clinical trials. These trials have revealed the complexity of using stem cells for cardiac repair, and considerations for using stem cells in the clinical setting are discussed in a subsequent section of this report.

The mechanism by which stem cells promote cardiac repair remains controversial, and it is likely that the cells regenerate myocardium through several pathways. Initially, scientists believed that transplanted cells differentiated into cardiac cells, blood vessels, or other cells damaged by CVD.911 However, this model has been recently supplanted by the idea that transplanted stem cells release growth factors and other molecules that promote blood vessel formation (angiogenesis) or stimulate quot;residentquot; cardiac stem cells to repair damage.1214 Additional mechanisms for stem-cell mediated heart repair, including strengthening of the post-infarct scar15 and the fusion of donor cells with host cardiomyocytes,16 have also been proposed.

Regardless of which mechanism(s) will ultimately prove to be the most significant in stem-cell mediated cardiac repair, cells must be successfully delivered to the site of injury to maximize the restored function. In preliminary clinical studies, researchers have used several approaches to deliver stem cells. Common approaches include intravenous injection and direct infusion into the coronary arteries. These methods can be used in patients whose blood flow has been restored to their hearts after a heart attack, provided that they do not have additional cardiac dysfunction that results in total occlusion or poor arterial flow.12, 17 Of these two methods, intracoronary infusion offers the advantage of directed local delivery, thereby increasing the number of cells that reach the target tissue relative to the number that will home to the heart once they have been placed in the circulation. However, these strategies may be of limited benefit to those who have poor circulation, and stem cells are often injected directly into the ventricular wall of these patients. This endomyocardial injection may be carried out either via a catheter or during open-heart surgery.18

To determine the ideal site to inject stem cells, doctors use mapping or direct visualization to identify the locations of scars and viable cardiac tissue. Despite improvements in delivery efficiency, however, the success of these methods remains limited by the death of the transplanted cells; as many as 90% of transplanted cells die shortly after implantation as a result of physical stress, myocardial inflammation, and myocardial hypoxia.4 Timing of delivery may slow the rate of deterioration of tissue function, although this issue remains a hurdle for therapeutic approaches.

Embryonic and adult stem cells have been investigated to regenerate damaged myocardial tissue in animal models and in a limited number of clinical studies. A brief review of work to date and specific considerations for the application of various cell types will be discussed in the following sections.

Because ES cells are pluripotent, they can potentially give rise to the variety of cell types that are instrumental in regenerating damaged myocardium, including cardiomyocytes, endothelial cells, and smooth muscle cells. To this end, mouse and human ES cells have been shown to differentiate spontaneously to form endothelial and smooth muscle cells in vitro19 and in vivo,20,21 and human ES cells differentiate into myocytes with the structural and functional properties of cardiomyocytes.2224 Moreover, ES cells that were transplanted into ischemically-injured myocardium in rats differentiated into normal myocardial cells that remained viable for up to four months,25 suggesting that these cells may be candidates for regenerative therapy in humans.

However, several key hurdles must be overcome before human ES cells can be used for clinical applications. Foremost, ethical issues related to embryo access currently limit the avenues of investigation. In addition, human ES cells must go through rigorous testing and purification procedures before the cells can be used as sources to regenerate tissue. First, researchers must verify that their putative ES cells are pluripotent. To prove that they have established a human ES cell line, researchers inject the cells into immunocompromised mice; i.e., mice that have a dysfunctional immune system. Because the injected cells cannot be destroyed by the mouse's immune system, they survive and proliferate. Under these conditions, pluripotent cells will form a teratoma, a multi-layered, benign tumor that contains cells derived from all three embryonic germ layers. Teratoma formation indicates that the stem cells have the capacity to give rise to all cell types in the body.

The pluripotency of ES cells can complicate their clinical application. While undifferentiated ES cells may possibly serve as sources of specific cell populations used in myocardial repair, it is essential that tight quality control be maintained with respect to the differentiated cells. Any differentiated cells that would be used to regenerate heart tissue must be purified before transplantation can be considered. If injected regenerative cells are accidentally contaminated with undifferentiated ES cells, a tumor could possibly form as a result of the cell transplant.4 However, purification methodologies continue to improve; one recent report describes a method to identify and select cardiomyocytes during human ES cell differentiation that may make these cells a viable option in the future.26

This concern illustrates the scientific challenges that accompany the use of all human stem cells, whether derived from embryonic or adult tissues. Predictable control of cell proliferation and differentiation requires additional basic research on the molecular and genetic signals that regulate cell division and specialization. Furthermore, long-term cell stability must be well understood before human ES-derived cells can be used in regenerative medicine. The propensity for genetic mutation in the human ES cells must be determined, and the survival of differentiated, ES-derived cells following transplantation must be assessed. Furthermore, once cells have been transplanted, undesirable interactions between the host tissue and the injected cells must be minimized. Cells or tissues derived from ES cells that are currently available for use in humans are not tissue-matched to patients and thus would require immunosuppression to limit immune rejection.18

While skeletal myoblasts (SMs) are committed progenitors of skeletal muscle cells, their autologous origin, high proliferative potential, commitment to a myogenic lineage, and resistance to ischemia promoted their use as the first stem cell type to be explored extensively for cardiac application. Studies in rats and humans have demonstrated that these cells can repopulate scar tissue and improve left ventricular function following transplantation.27 However, SM-derived cardiomyocytes do not function in complete concert with native myocardium. The expression of two key proteins involved in electromechanical cell integration, N-cadherin and connexin 43, are downregulated in vivo,28 and the engrafted cells develop a contractile activity phenotype that appears to be unaffected by neighboring cardiomyocytes.29

To date, the safety and feasibility of transplanting SM cells have been explored in a series of small studies enrolling a collective total of nearly 100 patients. Most of these procedures were carried out during open-heart surgery, although a couple of studies have investigated direct myocardial injection and transcoronary administration. Sustained ventricular tachycardia, a life-threatening arrhythmia and unexpected side-effect, occurred in early implantation studies, possibly resulting from the lack of electrical coupling between SM-derived cardiomyocytes and native tissue.30,31 Changes in preimplantation protocols have minimized the occurrence of arrhythmias in conjunction with the use of SM cells, and Phase II studies of skeletal myoblast therapy are presently underway.

In 2001, Jackson, et.al. demonstrated that cardiomyocytes and endothelial cells could be regenerated in a mouse heart attack model through the introduction of adult mouse bone marrow-derived stem cells.9 That same year, Orlic and colleagues showed that direct injection of mouse bone marrow-derived cells into the damaged ventricular wall following an induced heart attack led to the formation of new cardiomyocytes, vascular endothelium, and smooth muscle cells.11 Nine days after transplanting the stem cells, the newly-formed myocardium occupied nearly 70 percent of the damaged portion of the ventricle, and survival rates were greater in mice that received these cells than in those that did not. While several subsequent studies have questioned whether these cells actually differentiate into cardiomyocytes,32,33 the evidence to support their ability to prevent remodeling has been demonstrated in many laboratories.7

Based on these findings, researchers have investigated the potential of human adult bone marrow as a source of stem cells for cardiac repair. Adult bone marrow contains several stem cell populations, including hematopoietic stem cells (which differentiate into all of the cellular components of blood), endothelial progenitor cells, and mesenchymal stem cells; successful application of these cells usually necessitates isolating a particular cell type on the basis of its' unique cell-surface receptors. In the past three years, the transplantation of bone marrow mononuclear cells (BMMNCs), a mixed population of blood and cells that includes stem and progenitor cells, has been explored in more patients and clinical studies of cardiac repair than any other type of stem cell.7

The results from clinical studies of BMMNC transplantation have been promising but mixed. However, it should be noted that these studies have been conducted under a variety of conditions, thereby hampering direct comparison. The cells have been delivered via open-heart surgery and endomyocardial and intracoronary catheterization. Several studies, including the Bone Marrow Transfer to Enhance ST-Elevation Infarct Regeneration (BOOST) and the Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI) trials, have shown that intracoronary infusion of BMMNCs following a heart attack significantly improves the left ventricular (LV) ejection fraction, or the volume of blood pumped out of the left ventricle with each heartbeat.3436 However, other studies have indicated either no improvement in LV ejection fraction upon treatment37 or an increased LV ejection fraction in the control group.38 An early study that used endomyocardial injection to enhance targeted delivery indicated a significant improvement in overall LV function.39 Discrepancies such as these may reflect differences in cell preparation protocols or baseline patient statistics. As larger trials are developed, these issues can be explored more systematically.

Mesenchymal stem cells (MSCs) are precursors of non-hematopoietic tissues (e.g., muscle, bone, tendons, ligaments, adipose tissue, and fibroblasts) that are obtained relatively easily from autologous bone marrow. They remain multipotent following expansion in vitro, exhibit relatively low immunogenicity, and can be frozen easily. While these properties make the cells amenable to preparation and delivery protocols, scientists can also culture them under special conditions to differentiate them into cells that resemble cardiac myocytes. This property enables their application to cardiac regeneration. MSCs differentiate into endothelial cells when cultured with vascular endothelial growth factor40 and cardiomyogenic (CMG) cells when treated with the dna-demethylating agent, 5-azacytidine.41 More important, however, is the observation that MSCs can differentiate into cardiomyocytes and endothelial cells in vivo when transplanted to the heart following myocardial infarct (MI) or non-injury in pig, mouse, or rat models.4245 Additionally, the ability of MSCs to restore functionality may be enhanced by the simultaneous transplantation of other stem cell types.43

Several animal model studies have shown that treatment with MSCs significantly increases myocardial function and capillary formation.5,41 One advantage of using these cells in human studies is their low immunogenicity; allogeneic MSCs injected into infarcted myocardium in a pig model regenerated myocardium and reduced infarct size without evidence of rejection.46 A randomized clinical trial implanting MSCs after MI has demonstrated significant improvement in global and regional LV function,47 and clinical trials are currently underway to investigate the application of allogeneic and autologous MSCs for acute MI and myocardial ischemia, respectively.

Recent evidence suggests that the heart contains a small population of endogenous stem cells that most likely facilitate minor repair and turnover-mediated cell replacement.7 These cells have been isolated and characterized in mouse, rat, and human tissues.48,49 The cells can be harvested in limited quantity from human endomyocardial biopsy specimens50 and can be injected into the site of infarction to promote cardiomyocyte formation and improvements in systolic function.49 Separation and expansion ex vivo over a period of weeks are necessary to obtain sufficient quantities of these cells for experimental purposes. However, their potential as a convenient resource for autologous stem cell therapy has led the National Heart, Lung, and Blood Institute to fund forthcoming clinical trials that will explore the use of cardiac stem cells for myocardial regeneration.

The endothelium is a layer of specialized cells that lines the interior surface of all blood vessels (including the heart). This layer provides an interface between circulating blood and the vessel wall. Endothelial progenitor cells (EPCs) are bone marrow-derived stem cells that are recruited into the peripheral blood in response to tissue ischemia.4 EPCs are precursor cells that express some cell-surface markers characteristic of mature endothelium and some of hematopoietic cells.19,5153 EPCs home in on ischemic areas, where they differentiate into new blood vessels; following a heart attack, intravenously injected EPCs home to the damaged region within 48 hours.12 The new vascularization induced by these cells prevents cardiomyocyte apoptosis (programmed cell death) and LV remodeling, thereby preserving ventricular function.13 However, no change has been observed in non-infarcted regions upon EPC administration. Clinical trials are currently underway to assess EPC therapy for growing new blood vessels and regenerating myocardium.

Several other cell populations, including umbilical cord blood (UCB) stem cells, fibroblasts (cells that synthesize the extracellular matrix of connective tissues), and peripheral blood CD34+ cells, have potential therapeutic uses for regenerating cardiac tissue. Although these cell types have not been investigated in clinical trials of heart disease, preliminary studies in animal models indicate several potential applications in humans.

Umbilical cord blood contains enriched populations of hematopoietic stem cells and mesencyhmal precursor cells relative to the quantities present in adult blood or bone marrow.54,55 When injected intravenously into the tail vein in a mouse model of MI, human mononuclear UCB cells formed new blood vessels in the infarcted heart.56 A human DNA assay was used to determine the migration pattern of the cells after injection; although they homed only to injured areas within the heart, they were also detected in the marrow, spleen, and liver. When injected directly into the infarcted area in a rat model of MI, human mononuclear UCB cells improved ventricular function.57 Staining for CD34 and other markers found on the cell surface of hematopoietic stem cells indicated that some of the cells survived in the myocardium. Results similar to these have been observed following the injection of human unrestricted somatic stem cells from UCB into a pig MI model.58

Adult peripheral blood CD34+ cells offer the advantage of being obtained relatively easily from autologous sources.59 Although some studies using a mouse model of MI claim that these cells can transdifferentiate into cardiomyocytes, endothelial cells, and smooth muscle cells at the site of tissue injury,60 this conclusion is highly contested. Recent studies that involve the direct injection of blood-borne or bone marrow-derived hematopoietic stem cells into the infarcted region of a mouse model of MI found no evidence of myocardial regeneration following injection of either cell type.33 Instead, these hematopoietic stem cells followed traditional differentiation patterns into blood cells within the microenvironment of the injured heart. Whether these cells will ultimately find application in myocardial regeneration remains to be determined.

Autologous fibroblasts offer a different strategy to combat myocardial damage by replacing scar tissue with a more elastic, muscle-like tissue and inhibiting host matrix degradation.4 The cells may be manipulated to express muscle-specific transcription factors that promote their differentiation into myotubes such as those derived from skeletal myoblasts.61 One month after these cells were implanted into the post-infarction scar in a rat model of MI, they occupied a large portion of the scar but were not functionally integrated.61 Although the effects on ventricular function were not evaluated in this study, authors noted that modified autologous fibroblasts may ultimately prove useful in elderly patients who have a limited population of autologous skeletal myoblasts or bone marrow stem cells.

As these examples indicate, many types of stem cells have been applied to regenerate damaged myocardium. In select applications, stem cells have demonstrated sufficient promise to warrant further exploration in large-scale, controlled clinical trials. However, the current breadth of application of these cells has made it difficult to compare and contextualize the results generated by the various trials. Most studies published to date have enrolled fewer than 25 patients, and the studies vary in terms of cell types and preparations used, methods of delivery, patient populations, and trial outcomes. However, the mixed results that have been observed in these studies do not necessarily argue against using stem cells for cardiac repair. Rather, preliminary results illuminate the many gaps in understanding of the mechanisms by which these cells regenerate myocardial tissue and argue for improved characterization of cell preparations and delivery methods to support clinical applications.

Future clinical trials that use stem cells for myocardial repair must address two concerns that accompany the delivery of these cells: 1) safety and 2) tracking the cells to their ultimate destination(s). Although stem cells appear to be relatively safe in the majority of recipients to date, an increased frequency of non-sustained ventricular tachycardia, an arrhythmia, has been reported in conjunction with the use of skeletal myoblasts.30,6264 While this proarrhythmic effect occurs relatively early after cell delivery and does not appear to be permanent, its presence highlights the need for careful safety monitoring when these cells are used. Additionally, animal models have demonstrated that stem cells rapidly diffuse from the heart to other organs (e.g., lungs, kidneys, liver, spleen) within a few hours of transplantation,65,66 an effect observed regardless of whether the cells are injected locally into the myocardium. This migration may or may not cause side-effects in patients; however, it remains a concern related to the delivery of stem cells in humans. (Note: Techniques to label stem cells for tracking purposes and to assess their safety are discussed in more detail in other articles in this publication).

In addition to safety and tracking, several logistical issues must also be addressed before stem cells can be used routinely in the clinic. While cell tracking methodologies allow researchers to determine migration patterns, the stem cells must target their desired destination(s) and be retained there for a sufficient amount of time to achieve benefit. To facilitate targeting and enable clinical use, stem cells must be delivered easily and efficiently to their sites of application. Finally, the ease by which the cells can be obtained and the cost of cell preparation will also influence their transition to the clinic.

The evidence to date suggests that stem cells hold promise as a therapy to regenerate damaged myocardium. Given the worldwide prevalence of cardiac dysfunction and the limited availability of tissue for cardiac transplantation, stem cells could ultimately fulfill a large-scale unmet clinical need and improve the quality of life for millions of people with CVD. However, the use of these cells in this setting is currently in its infancymuch remains to be learned about the mechanisms by which stem cells repair and regenerate myocardium, the optimal cell types and modes of their delivery, and the safety issues that will accompany their use. As the results of large-scale clinical trials become available, researchers will begin to identify ways to standardize and optimize the use of these cells, thereby providing clinicians with powerful tools to mend a broken heart.

Chapter 5|Table of Contents|Chapter 7

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Mending a Broken Heart: Stem Cells and Cardiac Repair ...

Cardiac Stem Cells Comments Off on Mending a Broken Heart: Stem Cells and Cardiac Repair … | June 21st, 2018

Brief Summary:

This is a phase II, randomized, placebo-controlled clinical trial designed to assess feasibility, safety, and effect of autologous bone marrow-derived mesenchymal stem cells (MSCs) and c-kit+ cardiac stem cells (CSCs) both alone and in combination (Combo), compared to placebo (cell-free Plasmalyte-A medium) as well as each other, administered by transendocardial injection in subjects with ischemic cardiomyopathy.

This is a randomized, placebo-controlled clinical trial designed to evaluate the feasibility, safety, and effect of Combo, MSCs alone, and CSCs alone compared with placebo as well as each other in subjects with heart failure of ischemic etiology. Following a successful lead-in phase, a total of one hundred forty-four (144) subjects will be randomized (1:1:1:1) to receive Combo, MSCs, CSCs, or placebo. After randomization, baseline imaging, relevant harvest procedures, and study product injection, subjects will be followed up at 1 day, 1 week, 1 month, 3 months, 6 months and 12 months post study product injection. All subjects will receive study product injection (cells or placebo) using the NOGA XP Mapping and Navigation System. Subjects will have delayed-enhanced magnetic resonance imaging (DEMRI) scans to assess scar size and LV function and structure at baseline and at 6 and 12 months post study product administration. All endpoints will be assessed at the 6 and 12 month visits which will occur 180 30 days and 365 30 days respectively from the day of study product injection (Day 0). For the purpose of the endpoint analysis and safety evaluations, the Investigators will utilize an "intention-to-treat" study population, however an as treated analysis will also be conducted.

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Combination of Mesenchymal and C-kit+ Cardiac Stem Cells ...

Cardiac Stem Cells Comments Off on Combination of Mesenchymal and C-kit+ Cardiac Stem Cells … | June 21st, 2018

iPS Cells and Therapeutic Applications for Duchenne

We are currently in the optimization/validation phase of pre-clinical development.

This research is being done in the lab of Dr. Rita Perlingeiro at the University of Minnesota, in partnership with the University of Minnesota Center for Translational Medicine and the Molecular and Cellular Therapeutics Facility. This work is currently funded by the Department of Defense (DoD).

Induced pluripotent stem cells (iPS) are adult cells that have been reprogrammed to an embryonic stem cell-like state.There has been tremendous excitement for the therapeutic potential of iPS cells in treating genetic diseases. Our current research builds on our successful proof-of-principle studies for Duchenne performed with mouse wild-type and dystrophic iPS cells as well as control (healthy) human iPS cells. These studies demonstrate equivalent functional myogenic engraftment to that observed with their embryonic counterparts following their transplantation into dystrophic mice.

Our goal now is to apply this technology to clinical grade GMP-compliant iPS cells, and generate a cell product, iPS-derived myogenic progenitors, that can be delivered to muscular dystrophy patients.

Optimization of methodology, characterization of cell product, scalability with GMP-compliant method, followed by safety and efficacy studies. Once these have been achieved, we will be ready to move into a clinical trial.

2-3 years (it depends largely on how much funding we have available to conduct these studies).

University of Minnesota

In the first phase, adults with confirmed diagnosis of Duchenne (> 18 years old).

You can learn more about this research at the website for Dr. Perlingeiros lab: http://www.med.umn.edu/lhi/research/PerlingeiroLab/index.htm

http://www.ClinicalTrials.gov will post all clinical trials once they are actively recruiting patients.

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iPS Cell Therapy - Parent Project Muscular Dystrophy

IPS Cell Therapy Comments Off on iPS Cell Therapy – Parent Project Muscular Dystrophy | June 14th, 2018

To determine why the first stem cell trials were not providing the anticipated therapeutic potential, all variables, such as which stem cells were used, and how they were developed and administered, were open to consideration, says Dr. Epstein.

A key issue was the use of autologous stem cells in all previous studies. Studies demonstrated these old stem cells are functionally defective when compared to stem cells obtained from young healthy individuals. So harvesting a healthy young donors bone marrow and growing the resident stem cells might produce more robust cells.

However, giving a patient allogenic stem cells raised an important issue: whether such cells will be rejected by an immune response. But research showed mesenchymal stem cells (MSCs), a type of adult stem cell, have been designed by nature to be stealth bombers, explainsDr. Epstein. They express molecules on their surface that prevent the body from recognizing the cells as foreign, so the patient does not reject the donated MSCs.

To further explore and refine potential stem cell cardiovascular therapies, MHVI expanded the translational research team to include Michael Lipinski, MD, PhD, an expert in molecular biology and scientific lead for preclinical research at the MedStar Cardiovascular Research Network, and Dror Luger, PhD, an expert in immunology and inflammatory responses. By bringing together these diverse areas of expertise, we forged a team with the potential to produce research that could lead to important breakthroughs in understanding how stem cells might work and thereby provide more successful treatment of patients with cardiac disease, says Dr. Epstein.

CardioCell, a San Diego-based stem cell company focused on stem cell therapy for cardiovascular disease, found that MSCs grew faster and showed improved function when cultured in a reduced oxygen environment. Stem cells typically grow in the body, in bone marrow and other tissues, in a low oxygen environmentonly five percent oxygen, as opposed to room air, which is about 20 percent, explains Dr. Lipinski. All previous stem cell trials used cells exposed to, and grown under, room air oxygen conditions.

Using CardioCells low oxygen-grown MSCs, the MHVI scientists demonstrated biologically important effects occurred, even when the MSCs were administered intravenously. This mode of administration was previously rejected by scientists who thought cells would be trapped in the first capillary bed they traversedthe lungsand never reach the heart.

However, the MHVI team demonstrated a small percentage of these IV administered MSCs did reach the heart, where they could exert beneficial effects. The cells seek out inflamed cardiac tissue after a heart attack because they upregulate receptors that allow them to be attracted to and penetrate inflamed tissue in high numbers, says Dr. Luger.

The investigators also found the cells residing in other tissues could provide other benefits. It has been shown that a heart attack activates the immune and inflammatory systems, including those in the spleen, explains Dr. Luger. The systemic anti-inflammatory effects produced by MSCs in the spleen, lungs and other tissues caused by the molecules secreted by the MSCs could exert positive effects as well. Dr. Epstein added that such anti-inflammatory effects could also benefit the excessive inflammatory activities that exist in many heart failure patients.

For the clinical heart failure trial, MHVI is partnering with CardioCell, which will grow and provide stem cells already used in Phase I and 2a clinical trials and approved by the Food and Drug Administration.

As an extension of their stem cell work, the MHVI investigators are building on the fact that any beneficial effect of adult stem cells will not derive from their transformation into heart muscle, but rather from the molecules they secrete; these, in turn, stimulate pathways favoring tissue healing. The team is investigating the use of liposomes as therapeutic delivery vehicles for these secreted products, which include those with anti-inflammatory and angiogenesis activities.

If successful, using MSCs for anti-inflammatory and immune-modulatory effects could have implicationsfor many different diseases, including arthritis and autoimmune diseases like rheumatoid arthritis. Dr. Epstein cautions that a great deal of research is yet to be done before such applications can be routinely used to treat patients with these conditions. For now, they hope the current studies in heart failure patients will demonstrate effectiveness. If so, Dr. Epstein says, it changes the whole playing field for stem cells.

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Next Steps for Cardiac Stem Cells - MedStar Heart ...

Cardiac Stem Cells Comments Off on Next Steps for Cardiac Stem Cells – MedStar Heart … | June 11th, 2018

Stem cells have the incredible ability to develop into a variety of different cell types within the body. In addition, stem cells can play a crucial role in internally repairing many types of tissues. During this process, stem cells divide, replenishing other cells without limit.

While stem cells have been used by medical professionals for a wide variety of reasons in order to treat injuries, ailments, and diseases affecting every part of the body, the use of stem cells in the treatment of spinal damage may be the most exciting and potent use yet. Through the application of these spinal treatments, patients have the ability to recover not only more completely, but also in a more natural and therefore more complete manner than ever before. When paired with the insight of a skilled spinal surgeon, the results can be astonishing.

If you or a loved one is suffering from spine damage and are looking to learn more about how stem cell treatments can help you, get in touch with the expert back team at ProMed SPINE today by filling out ouronline contact form. Schedule a consultation with us and begin the path to recovery today!

Stem cells differ from other cell types because they are unspecialized and therefore capable of renewing themselves through cell division. Under certain physiologic or experimental conditions, they have the ability to become tissue or even organ-specific cells with special functions. Given these unique regenerative abilities, stem cells offer new potential in the enhancement of every surgery.

Rather then undergoing an invasive surgery that wont actually repair damage from degenerative disc disease, stem cell spinal treatments are short, minimally invasive and capable of healing the damage that has been done to the disc. Stem cell therapy produces new disc cells inside the disc itself, allowing it to rebuild to a like-new condition. When treating degenerative disc disease, bone marrow is extracted from the patients hipbone and stem cells are filtered out using a centrifuge. Then stem cells are injected into the disc with the help of an x-ray. After this step, the patient is free to go home and begin the recovery process. Over the next few months to a year, patients will experience a lessening of back pain as the disc begins to restore itself. It is quite common for patients who have undergone stem cell injections to experience complete relief from back pain and a vast improvement in their overall quality of life.

Stem cells can also be used to enhance the effects of a spinal fusion surgery. A lack of useful new bone growth after this type of surgery can be a significant problem. This new technology helps patients grow new bone and avoid harvesting a bone graft from the patients own hip or using bone from a deceased donor. By avoiding these steps, patients are able to recover faster and prevent painful procedures.

A major component of stem cells is their ability to reinforce stronger, healthier healing in patients. Oftentimes, the body is in a weakened state following a surgical procedure and therefore more susceptible to developing infection. Stem cells unique ability to replenish themselves offers the body fresh, healthy cells that are not nearly as vulnerable to incurring infection so that the body can heal more quickly and effectively.

After undergoing a surgery and the rehabilitation process that follows, many patients are left with unsightly scars. These scars are often painful reminders of a traumatic event and, in some cases, cause self-consciousness or outright embarrassment due to their appearance. Stem cells have become an increasingly useful aid in ridding patients of unattractive scars so that they can fully recover from their injuries. Stem cells are useful in the treatment of scarring in three major ways: they carry anti-inflammatory properties that prevent excessive scarring, are capable of replenishing normal cells in the tissue through differentiation, and finally, stem cells dissolve the excess collagen in scar tissue by emitting large amounts of enzymes whose specific function is to dissolve scar tissue.

Click here to learnmore about stem cell therapy from WebMD.com.

The potential medical benefits of stem cell research are unparalleled in the healing and rejuvenating processes following a spinal procedure. Whether you are facing a major surgery or are considering your options concerning continued pain and physical limitations, knowing what options may be best for you is vital in the search for skilled medical care. Schedule an appointment with a laser spine surgeonto find out how stem cell therapy can be used to help you find a healthier and happier life.

Next, please read about disc replacement surgery.

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Spinal Surgery Stem Cell Treatment | ProMedSPINE

Spinal Cord Stem Cells Comments Off on Spinal Surgery Stem Cell Treatment | ProMedSPINE | June 9th, 2018

Update: January 2018

Background information:One of the biggest issues preventing recovery after achronicspinal cord injury is the scar that appears a few days or weeks after the injury and prevents any axon from growing away from the lesion area. One of the key scar reduction strategies involves using the Chondroitinase enzyme.

In this chapter we are also covering the therapeutic strategies that are used to neutralize growth inhibitors (often referred to as NoGo) after the spinal cord injury, and /or promote nerve growth.

The intrathecal delivery of the NoGo Trap protein delivery has shown axonal growth associated with a certain recovery of function by rats. It is reported to promote nerve sprouting and synaptic plasticity, as well as, to a lesser extent, axonal regeneration. The ReNetX company is now planning a clinical trial for cervical injury patients.

Input from Spinal Research, who initiated the project: since 2014, the CHASE-IT consortium has achieved several critical milestones by working on, and overcoming, many of the issues related to creating a safe gene therapy for chondroitinase:

-The gene for chondroitinase can now be expressed in an active form in human cells-Expression of chondroitinase in the spinal cord can now be controlled, switching it on and off using an inducible switch responsive to the antibiotic doxycycline-Treatment gives rise to improved walking and unprecedented upper limb function in clinically-relevant spinal cord injury models

-Demonstrate inducible chondroitinase gene therapy works in chronic injuries-Transfer the inducible gene therapy machinery developed in the lentiviral vector to the more clinically-acceptable Adeno-associated viral (AAV) vector-Eliminate any background expression of chondroitinase when system in the uninduced off state-Confirm chondroitinase-AAV retains comparable efficacy as chondroitinase-L

-UK:alternative delivery method for Chase. More info: here-CANADA:alternativedelivery method for Chase.-USA:studyof non-human primates.-USA: Rose Bengal Study by Dr. A. Parr (University of Minnesota). See January 2018 publication

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Cure Spinal Cord injury Research, therapies, treatments, 2018

Spinal Cord Stem Cells Comments Off on Cure Spinal Cord injury Research, therapies, treatments, 2018 | June 3rd, 2018

The human body comprises more than 200 types of cells, and every one of these cell types arises from the zygote, the single cell that forms when an egg is fertilized by a sperm. Within a few days, that single cell divides over and over again until it forms a blastocyst, a hollow ball of 150 to 200 cells that give rise to every single cell type a human body needs to survive, including the umbilical cord and the placenta that nourishes the developing fetus.

Each cell type has its own size and structure appropriate for its job. Skin cells, for example, are small and compact, while nerve cells that enable you to wiggle your toes have long, branching nerve fibers called axons that conduct electrical impulses.

Cells with similar functionality form tissues, and tissues organize to form organs. Each cell has its own job within the tissue in which it is found, and all of the cells in a tissue and organ work together to make sure the organ functions properly.

Regardless of their size or structure, all human cells start with these things in common:

Stem cells are the foundation of development in plants, animals and humans. In humans, there are many different types of stem cells that come from different places in the body or are formed at different times in our lives. These include embryonic stem cells that exist only at the earliest stages of development and various types of tissue-specific (or adult) stem cells that appear during fetal development and remain in our bodies throughout life.

Stem cells are defined by two characteristics:

Beyond these two things, though, stem cells differ a great deal in their behaviors and capabilities.

Embryonic stem cells are pluripotent, meaning they can generate all of the bodys cell types but cannot generate support structures like the placenta and umbilical cord.

Other cells are multipotent, meaning they can generate a few different cell types, generally in a specific tissue or organ.

As the body develops and ages, the number and type of stem cells changes. Totipotent cells are no longer present after dividing into the cells that generate the placenta and umbilical cord. Pluripotent cells give rise to the specialized cells that make up the bodys organs and tissues. The stem cells that stay in your body throughout your life are tissue-specific, and there is evidence that these cells change as you age, too your skin stem cells at age 20 wont be exactly the same as your skin stem cells at age 80.

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Stem Cell Basics

Skin Stem Cells Comments Off on Stem Cell Basics | June 3rd, 2018

When burn victims need a skin graft they typically have to grow skin on other parts of their bodies - a process that can take weeks. A new technique uses stem cells derived from the umbilical cord to generate new skin much more quickly. The results were published in Stem Cells Translational Medicine by lead author Ingrid Garzn from the University of Granadas Department of Histology.

Not only can the stem cells develop artificial skin more quickly than regular normal skin growth, but the skin can also be stored so it is ready right when it is needed. Tens of thousands of grafts are performed each year for burn victims, cosmetic surgery patients, and for people with large wounds having difficulty healing. Traditionally, this involves taking a large patch of skin (typically from the thigh) and removing the dermis and epidermis to transplant elsewhere on the body.

The artificial skin requires the use of Wharton's jelly mesenchymal stem cells. As the name implies, Whartons jelly is a gelatinous tissue in the umbilical cord that contains uncommitted mesenchymal stemcells (MSC). The MSC is then combined with agarose(a polysaccharide polymer) and fibrin (the fibrous protein that aids in blood clotting). This yielded two results: skin and the mucosal lining of the mouth. The researchers are very pleased to have found two new uses for the stem cells of Whartons jelly, which have not previously been researched for epithelial applications.

Once the epithelial tissues have been created, researchers can store it in tissue banks. If someone is brought into the hospital following a devastating burn or accident, the tissue is ready to graft immediately; not in a few weeks. However, the stem-cell skin is not able to fully differentiate in vitro. After the graft, it has complete cell-cell junctions and will develop all of the necessary layers of normal epithelial tissue.

The MSCs are taken from the umbilical cord after the baby has been born, which poses no risk to either the mother or the child. This method is relatively inexpensive and has been shown to be more efficient than stem cells derived from bone marrow.

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Stem Cells Can Create Skin For Burn Victims | IFLScience

Skin Stem Cells Comments Off on Stem Cells Can Create Skin For Burn Victims | IFLScience | May 20th, 2018

The spinal cord is a collection of nerve fibres and other tissues contained with the spine. The nerves within the spinal cord connect the peripheral nervous system to the brain forming the central nervous system. The spinal cord is essential for the transmission and reception of electrical messages to and from the brain to other areas of the body. Should the spinal cord become damaged, the impacts can be devastating or even fatal.

Preventable causes such as violence, falls and road traffic accents account for the majority of spinal cord injuries. Every year, between 250,000 and 500,000 people suffer a spinal cord injury globally. Unfortunately, those with a spinal cord injury are 2 to 5 times more likely to suffer premature death than those without.[1]

A spinal cord injury can affect anyone at any time and unfortunately there is currently no effective treatment available to those with a spinal cord injury.

The cost of spinal cord injury to the UK alone is estimated at 1 billion per annum.[2]

While there is currently no effective treatment for spinal cord injury available to the general public, stem cells could hold the key to successful spinal cord repair in the future. A British professor, Geoffrey Raisman, headed research which used stem cells to enable a paralysed man to walk again.

The research used a type of stem cell called olfactory ensheathing cells (OECs) from the nose of the patient and transplanted them into the spinal cord. OECs are specialist cells which form part of the sense of smell enabling nerve fibres in the olfactory system to continually renew. It was previously thought that severed nerve fibres in the spinal cord were unable to repair themselves. However, once OECs have been transplanted into the spinal cord it appears they facilitate the growth of the ends of severed nerve fibres and even enable them join together.[6]

In addition to Raismans research, Dr. Carlos Lima of Portugal had transplanted olfactory stem cells to treat spinal cord injury in over 100 patients. Lima and his team showed that a few patients were able to regain some motor function and sensation thanks to the transplanted olfactory stem cells.[7]

Promisingly, there are currently 38 clinical trials investigating the application of stem cells in spinal cord injury.[8]

The information contained in this article is for information purposes only and is not intended to replace the advice of a medical expert. If you have any concerns about your health we urge you to discuss them with your doctor.

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Spinal Cord Injury and Stem Cells | Cells4Life

Spinal Cord Stem Cells Comments Off on Spinal Cord Injury and Stem Cells | Cells4Life | May 4th, 2018

12.15.17CIRM Grants ViaCyte $1.4M to Create Immune-Evasive Pluripotent Stem Cell Lines

SAN DIEGO, December 15, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, today announced that the California Institute for Regenerative Medicine (CIRM) approved a grant of $1.4 million to support the initial development of []

ViaCyte is developing PEC-Direct to address the urgent medical need of high-risk type 1 diabetes and provide a potentially life-saving therapy SAN DIEGO,December 6, 2017 ViaCyte today announced that CONNECT, a premier innovation company []

SAN DIEGO, October 4, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, today announced upcoming company presentations at the Cell and Gene Meeting on the Mesa and the BIO Investor Forum. In addition, ViaCyte []

SAN DIEGO, September 28, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, today announced that the California Institute for Regenerative Medicine (CIRM) approved a grant of $20 million to support the clinical development of []

Developing PEC-Direct to address urgent medical need in patients with high-risk type 1 diabetes SAN DIEGO, September 21, 2017 Today, ViaCyte announced that its PEC-Direct product candidate has been selected as one of three []

SAN DIEGO, September 7, 2017 ViaCyte, Inc., a privately-held, leading regenerative medicine company, today announced upcoming scientific presentations. ViaCyte is developing novel stem cell-derived islet replacement therapies for insulin-requiring diabetes. ViaCytes product candidates have []

San Diego, August 1, 2017 ViaCyte, Inc., a privately-held, leading regenerative medicine company, announced today that the first patients have been implanted with the PEC-Direct product candidate, a novel islet cell replacement therapy in []

SAN DIEGO, June 15, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, today announced a presentation at the International Society for Stem Cell Research (ISSCR) 2017 Annual Meeting in Boston. ViaCyte is developing novel []

San Diego, May 22, 2017 ViaCyte, Inc., a privately-held leading regenerative medicine company, announced today that the U.S. Food and Drug Administration (FDA) has allowed the companys Investigational New Drug Application (IND) for the []

San Diego, May 22, 2017 ViaCyte, Inc., a privately-held leading regenerative medicine company, announced today $10 million in financing to support operations. Participants in the financing included Asset Management Partners, W.L. Gore & Associates, []

New York and San Diego, May 22, 2017 ViaCyte, Inc., a privately-held leading regenerative medicine company, and JDRF, the leading global organization funding type 1 diabetes research, jointly announced today JDRF grant funding to []

ViaCyte to also present at World Advanced Therapies and Regenerative Medicine Congress in London SAN DIEGO, April 24, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, today announced two presentations on April 27 at []

SAN DIEGO, California and NEWARK, Delaware, March 29, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, and W. L. Gore & Associates, Inc. (Gore), a global materials science company, today announced a collaborative research []

SAN DIEGO and SAN FRANCISCO, February 23, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, and Beyond Type 1, a not-for-profit advocacy and education group for those living with type 1 diabetes, today []

SAN DIEGO, February 21, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, today announced four presentations at upcoming healthcare events. ViaCyte is advancing two novel cell replacement therapies as long-term diabetes treatments. ViaCytes product []

President and CEO, Paul Laikind, PhD to present at 2017 Biotech Showcase SAN DIEGO, January 4, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, today announced the addition of twenty-two new patents in 2016. []

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Press Releases Viacyte, Inc.

IPS Cell Therapy Comments Off on Press Releases Viacyte, Inc. | April 29th, 2018

Advanced Therapy with Advanced Results

Since 1968, the medical community has been harnessing the incredible healing, and regenerative power of bone marrow-derived stem cells. Bone Marrow Derived Stem Cell Therapy takes stem cells isolated from your bone marrow and relocates them to heal, regenerate and treat damaged areas and chronic conditions. This revolutionary technology is a result of decades of evidence-based research and advancements in the area of stem cells.

A process called hematopoiesis, which occurs inside your bones, has been working to grow and regenerate cells in your body since you were in the womb. The human body is in constant high demand for blood cells, so the hematopoiesis process stays hard at work to produce. During hematopoiesis, hematopoietic stem cells are produced with the raw potential power to develop into white blood cells, red blood cells, and platelets. Blood cells are vital to immune function and healing, so these stem cells are rich in growth factors that facilitate the repair and replacement of damaged cells. Mesenchymal stem cells are also found in bone marrow. Mesenchymal stem cells are reserved adult stem cells that help facilitate the regeneration of tissue naturally in the body. They are an integral part of wound healing, regulation of aging, and stabilizing vital organs. These mesenchymal stem cells are considered to be raw potential meaning they can differentiate into the tissue cells needed in a specific area. These mesenchymal stem cells have the potential to repair damaged cartilage, bone, tendons, muscle, skin, and connective cell tissue.

Stem cell therapy is one of the newest and most cutting-edge therapies for chronic joint pain. Using this therapy, our providers offer patients essential properties for healing and restoring joint health:

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Bone Marrow-Derived Stem Cell Therapy Milwaukee, WI ...

Bone Marrow Stem Cells Comments Off on Bone Marrow-Derived Stem Cell Therapy Milwaukee, WI … | April 27th, 2018