The skin

In humans and other mammals, the skin has three parts - the epidermis, the dermis and the subcutis (or hypodermis). The epidermis forms the surface of the skin. It is made up of several layers of cells called keratinocytes. The dermis lies underneath the epidermis and contains skin appendages: hair follicles, sebaceous (oil) glands and sweat glands. The subcutis contains fat cells and some sweat glands.

The skin and its structure: The skin has three main layers - the epidermis, dermis and subcutis. The epidermis contains layers of cells called keratinocytes. BL = basal layer; SL = spinous layer; GL = granular layer; SC= stratum corneum. Image adapted by permission from Macmillan Publishers Ltd: Nature Reviews Genetics 3, 199-209 (March 2002), Getting under the skin of epidermal morphogenesis, Elaine Fuchs & Srikala Raghavan; doi:10.1038/nrg758; Copyright 2002.

In everyday life your skin has to cope with a lot of wear and tear. For example, it is exposed to chemicals like soap and to physical stresses such as friction with your clothes or exposure to sunlight. The epidermis and skin appendages need to be renewed constantly to keep your skin in good condition. Whats more, if you cut or damage your skin, it has to be able to repair itself efficiently to keep doing its job protecting your body from the outside world.

Skin stem cells make all this possible. They are responsible for constant renewal (regeneration) of your skin, and for healing wounds. So far, scientists have identified several different types of skin stem cell:

Some studies have also suggested that another type of stem cell, known as mesenchymal stem cells, can be found in the dermis and hypodermis. This remains controversial amongst scientists and further studies are needed to determine whether these cells are truly mesenchymal stem cells and what their role is in the skin.

Epidermal stem cells are one of the few types of stem cell already used to treat patients. Thanks to a discovery made in 1970 by Professor Howard Green in the USA, epidermal stem cells can be taken from a patient, multiplied and used to grow sheets of epidermis in the lab. The new epidermis can then be transplanted back onto the patient as a skin graft. This technique is mainly used to save the lives of patients who have third degree burns over very large areas of their bodies. Only a few clinical centres are able to carry out the treatment successfully, and it is an expensive process. It is also not a perfect solution. Only the epidermis can be replaced with this method; the new skin has no hair follicles, sweat glands or sebaceous glands.

One of the current challenges for stem cell researchers is to understand how all the skin appendages are regenerated. This could lead to improved treatments for burn patients, or others with severe skin damage.

Researchers are also working to identify new ways to grow skin cells in the lab. Epidermal stem cells are currently cultivated on a layer of cells from rodents, called murine cells. These cell culture conditions have been proved safe, but it would be preferable to avoid using animal products when cultivating cells that will be transplanted into patients. So, researchers are searching for effective cell culture conditions that will not require the use of murine cells.

Scientists are also working to treat genetic diseases affecting the skin. Since skin stem cells can be cultivated in laboratories, researchers can genetically modify the cells, for example by inserting a missing gene. The correctly modified cells can be selected, grown and multiplied in the lab, then transplanted back onto the patient. Epidermolysis Bullosa is one example of a genetic skin disease that might benefit from this approach. Work is underway to test the technique.

The rest is here:
Skin stem cells: where do they live and what can they do? | Europe ...

In 2006, Shinya Yamanaka of Kyoto University in Japan was the first to disprove the previous notion that reversible cell differentiation of mammals was impossible. He reprogrammed a fully differentiated mouse cell into a pluripotent stem cell by introducing four genes, Oct-4, SOX2, KLF4, and Myc, into the mouse fibroblast through gene-carrying viruses. With this method, he and his coworkers created induced pluripotent stem cells (iPS cells), the key component in this experiment.[1] Scientists have been able to conduct experiments that show the ability of iPS cells to treat and even cure diseases. In this experiment, tests were run on mice with inherited sickle cell anemia.Skin cells were turned into cells containing genes that transformed the cells into iPS cells. These replaced the diseased sickled cells, curing the test mice. The reprogramming of the pluripotent stem cells in mice was successfully duplicated with human pluripotent stem cells within about a year of the experiment on the mice.

Sickle cell anemia is a disease in which the body produces abnormally shaped red blood cells. Red blood cells are flexible and round, moving easily through the blood vessels. Infected cells are shaped like a crescent or sickle (the namesake of the disease). As a result of this disorder the hemoglobin protein in red blood cells is faulty. Normal hemoglobin bonds to oxygen, then releases it into cells that need it. The blood cell retains its original form and is cycled back to the lungs and re-oxygenated.

Sickle cell hemoglobin, however, after giving up oxygen, cling together and make the red blood cell stiff. The sickle shape also makes it difficult for the red blood cell to navigate arteries and causes blockages.[2] This can cause intense pain and organ damage. The sickled red blood cells are fragile and prone to rupture. When the number of red blood cells decreases from rupture (hemolysis), anemia is the result. Sickle cells also die in 1020 days as opposed to the traditional 120-day lifespan of a normal red blood cell.

Sickle cell anemia is inherited as an autosomal (meaning that the gene is not linked to a sex chromosome) recessive condition.[2] This means that the gene can be passed on from a carrier to his or her children. In order for sickle cell anemia to affect a person, the gene must be inherited from both the mother and the father, so that the child has two recessive sickle cell genes (a homozygous inheritance). People who inherit one sickle cell gene from one parent and one normal gene from the other parent, i.e. heterozygous patients, have a condition called sickle cell trait. Their bodies make both sickle hemoglobin and normal hemoglobin. They may pass the trait on to their children.

The effects of sickle cell anemia vary from person to person. People who have the disease suffer from varying degrees of chronic pain and fatigue. With proper care and treatment, the quality of health of most patients will improve. Doctors have learned a great deal about sickle cell anemia since its discovery in 1979. They know its causes, its effects on the body, and possible treatments for complications. Sickle cell anemia has no widely available cure. A bone marrow transplant is the only treatment method currently recognized to be able to cure the disease, though it does not work for every patient. Finding a donor is difficult and the procedure could potentially do more harm than good. Treatments for sickle cell anemia are generally aimed at avoiding crises, relieving symptoms, and preventing complications. Such treatments may include medications, blood transfusions, and supplemental oxygen.

During the first step of the experiment, skin cells (also known as fibroblasts) were collected from infected test mice and put in a culture. The fibroblasts were reprogrammed by infecting them with retroviruses that contained genes common to embryonic stem cells. These genes were the same four used by Yamanaka (Oct-4, SOX2, KLF4, and Myc) in his earlier study. The investigators were trying to produce cells with the potential to differentiate into any type of cell needed (i.e. pluripotent stem cells). As the experiment continued, the fibroblasts multiplied into identical copies of iPS cells. The cells were then treated to form the mutation needed to reverse the anemia in the mice. This was accomplished by restructuring the DNA containing the defective globin gene into DNA with the normal gene through the process of homologous recombination. The iPS cells then differentiated into blood stem cells, or hematopoietic stem cells. The hematopoietic cells were injected back into the infected mice, where they proliferate and differentiate into normal blood cells, curing the mice of the disease.[3][4][verification needed]

To determine whether the mice were cured from the disease, the scientists checked for the usual symptoms of sickle cell disease. They examined the blood for mean corpuscular volume (MCV) and red cell distribution width (RDW) and urine concentration defects. They also checked for sickled red blood cells. They examined the DNA through gel electrophoresis, checking for bands that display an allele that causes sickling. Compared to the untreated mice with the disease, which they used as a control, the treated animals had marked increases in RBC counts, healthy hemoglobin, and packed cell volume levels.[5]

Researchers examined the urine concentration defect, which results from RBC sickling in renal tubules and consequent reduction in renal medullary blood flow, and the general deteriorated systemic condition reflected by lower body weight and increased breathing.[5] They were able to see that these parts of the body of the mice had healed or improved. This indicated that all hematological and systemic parameters of sickle cell anemia improved substantially and were comparable to those in control mice.[5] They cannot say if this will work in humans because a safe way to inject the genes for the induced pluripotent cells is still needed.[citation needed]

The reprogramming of the induced pluripotent stem cells in mice was successfully duplicated in humans within a year of the successful experiment on the mice. This reprogramming was done in several labs and it was shown that the iPS cells in humans were almost identical to original embryonic stem cells (ES cells) that are responsible for the creation of all structures in a fetus.[1] An important feature of iPS cells is that they can be generated with cells taken from an adult, which would circumvent many of the ethical problems associated with working with ES cells. These iPS cells also have potential in creating and examining new disease models and developing more efficient drug treatments.[6] Another feature of these cells is that they provide researchers with a human cell sample, as opposed to simply using an animal with similar DNA, for drug testing.

One major problem with iPS cells is the way in which the cells are reprogrammed. Using gene-carrying viruses has the potential to cause iPS cells to develop into cancerous cells.[1] Also, an implant made using undifferentiated iPS cells, could cause a teratoma to form. Any implant that is generated from using these iPS cells would only be viable for transplant into the original subject that the cells were taken from. In order for these iPS cells to become viable in therapeutic use, there are still many steps that must be taken.[5][7]

Read more from the original source:
IPS Cell Therapy - Genetherapy

In 2006, Shinya Yamanaka of Kyoto University in Japan was the first to disprove the previous notion that reversible cell differentiation of mammals was impossible. He reprogrammed a fully differentiated mouse cell into a pluripotent stem cell by introducing four genes, Oct-4, SOX2, KLF4, and Myc, into the mouse fibroblast through gene-carrying viruses. With this method, he and his coworkers created induced pluripotent stem cells (iPS cells), the key component in this experiment.[1] Scientists have been able to conduct experiments that show the ability of iPS cells to treat and even cure diseases. In this experiment, tests were run on mice with inherited sickle cell anemia.Skin cells were turned into cells containing genes that transformed the cells into iPS cells. These replaced the diseased sickled cells, curing the test mice. The reprogramming of the pluripotent stem cells in mice was successfully duplicated with human pluripotent stem cells within about a year of the experiment on the mice.

Sickle cell anemia is a disease in which the body produces abnormally shaped red blood cells. Red blood cells are flexible and round, moving easily through the blood vessels. Infected cells are shaped like a crescent or sickle (the namesake of the disease). As a result of this disorder the hemoglobin protein in red blood cells is faulty. Normal hemoglobin bonds to oxygen, then releases it into cells that need it. The blood cell retains its original form and is cycled back to the lungs and re-oxygenated.

Sickle cell hemoglobin, however, after giving up oxygen, cling together and make the red blood cell stiff. The sickle shape also makes it difficult for the red blood cell to navigate arteries and causes blockages.[2] This can cause intense pain and organ damage. The sickled red blood cells are fragile and prone to rupture. When the number of red blood cells decreases from rupture (hemolysis), anemia is the result. Sickle cells also die in 1020 days as opposed to the traditional 120-day lifespan of a normal red blood cell.

Sickle cell anemia is inherited as an autosomal (meaning that the gene is not linked to a sex chromosome) recessive condition.[2] This means that the gene can be passed on from a carrier to his or her children. In order for sickle cell anemia to affect a person, the gene must be inherited from both the mother and the father, so that the child has two recessive sickle cell genes (a homozygous inheritance). People who inherit one sickle cell gene from one parent and one normal gene from the other parent, i.e. heterozygous patients, have a condition called sickle cell trait. Their bodies make both sickle hemoglobin and normal hemoglobin. They may pass the trait on to their children.

The effects of sickle cell anemia vary from person to person. People who have the disease suffer from varying degrees of chronic pain and fatigue. With proper care and treatment, the quality of health of most patients will improve. Doctors have learned a great deal about sickle cell anemia since its discovery in 1979. They know its causes, its effects on the body, and possible treatments for complications. Sickle cell anemia has no widely available cure. A bone marrow transplant is the only treatment method currently recognized to be able to cure the disease, though it does not work for every patient. Finding a donor is difficult and the procedure could potentially do more harm than good. Treatments for sickle cell anemia are generally aimed at avoiding crises, relieving symptoms, and preventing complications. Such treatments may include medications, blood transfusions, and supplemental oxygen.

During the first step of the experiment, skin cells (also known as fibroblasts) were collected from infected test mice and put in a culture. The fibroblasts were reprogrammed by infecting them with retroviruses that contained genes common to embryonic stem cells. These genes were the same four used by Yamanaka (Oct-4, SOX2, KLF4, and Myc) in his earlier study. The investigators were trying to produce cells with the potential to differentiate into any type of cell needed (i.e. pluripotent stem cells). As the experiment continued, the fibroblasts multiplied into identical copies of iPS cells. The cells were then treated to form the mutation needed to reverse the anemia in the mice. This was accomplished by restructuring the DNA containing the defective globin gene into DNA with the normal gene through the process of homologous recombination. The iPS cells then differentiated into blood stem cells, or hematopoietic stem cells. The hematopoietic cells were injected back into the infected mice, where they proliferate and differentiate into normal blood cells, curing the mice of the disease.[3][4][verification needed]

To determine whether the mice were cured from the disease, the scientists checked for the usual symptoms of sickle cell disease. They examined the blood for mean corpuscular volume (MCV) and red cell distribution width (RDW) and urine concentration defects. They also checked for sickled red blood cells. They examined the DNA through gel electrophoresis, checking for bands that display an allele that causes sickling. Compared to the untreated mice with the disease, which they used as a control, the treated animals had marked increases in RBC counts, healthy hemoglobin, and packed cell volume levels.[5]

Researchers examined the urine concentration defect, which results from RBC sickling in renal tubules and consequent reduction in renal medullary blood flow, and the general deteriorated systemic condition reflected by lower body weight and increased breathing.[5] They were able to see that these parts of the body of the mice had healed or improved. This indicated that all hematological and systemic parameters of sickle cell anemia improved substantially and were comparable to those in control mice.[5] They cannot say if this will work in humans because a safe way to inject the genes for the induced pluripotent cells is still needed.[citation needed]

The reprogramming of the induced pluripotent stem cells in mice was successfully duplicated in humans within a year of the successful experiment on the mice. This reprogramming was done in several labs and it was shown that the iPS cells in humans were almost identical to original embryonic stem cells (ES cells) that are responsible for the creation of all structures in a fetus.[1] An important feature of iPS cells is that they can be generated with cells taken from an adult, which would circumvent many of the ethical problems associated with working with ES cells. These iPS cells also have potential in creating and examining new disease models and developing more efficient drug treatments.[6] Another feature of these cells is that they provide researchers with a human cell sample, as opposed to simply using an animal with similar DNA, for drug testing.

One major problem with iPS cells is the way in which the cells are reprogrammed. Using gene-carrying viruses has the potential to cause iPS cells to develop into cancerous cells.[1] Also, an implant made using undifferentiated iPS cells, could cause a teratoma to form. Any implant that is generated from using these iPS cells would only be viable for transplant into the original subject that the cells were taken from. In order for these iPS cells to become viable in therapeutic use, there are still many steps that must be taken.[5][7]

Read more from the original source:
Induced pluripotent stem cell therapy - Wikipedia, the free ...

PUBLIC RELEASE DATE:

7-Nov-2013

Contact: B. D. Colen bd_colen@harvard.edu 617-495-7821 Harvard University

Harvard Stem Cell Scientists have discovered that the same chemicals that stimulate muscle development in zebrafish can also be used to differentiate human stem cells into muscle cells in the laboratory, an historically challenging task that, now overcome, makes muscle cell therapy a more realistic clinical possibility.

The work, published this week in the journal Cell, began with a discovery by Boston Children's Hospital researchers, led by Leonard Zon, MD, and graduate student Cong (Tony) Xu, who tested 2,400 different chemicals in cultures of zebrafish embryo cells to determine if any could increase the numbers of muscle cells formed. Using fluorescent reporter fish in which muscle cells were visible during their creation, the researchers found six chemicals that were very effective at promoting muscle formation.

Zon shared his results with Harvard Department of Stem Cell and Regenerative Biology professor Amy Wagers, PhD, and Mohammadsharif Tabebordbar, a graduate student in her laboratory, who tested the six chemicals in mice. One of the six, called forskolin, was found to increase the numbers of muscle stem cells from mice that could be obtained when these cells were grown in laboratory dishes. Moreover, the cultured cells successfully integrated into muscle when transplanted back into mice.

Inspired by the successful application of these chemicals in mice, Salvatore Iovino, PhD, a joint postdoctoral fellow in the Wagers lab and the lab of C. Ronald Kahn, MD, at the Joslin Diabetes Center, investigated whether the chemicals would also affect human cells and found that a combination of three chemicals, including forskolin, could induce differentiation of human induced pluripotent stem (iPS) cells, made by reprogramming skin cells. Exposure of iPS cells to these chemicals converted them into skeletal muscle, an outcome the Wagers and Kahn labs had been striving to achieve for years using conventional methods. When transplanted into a mouse, the human iPS-derived muscle cells also contributed to muscle repair, offering early promise that this protocol could provide a route to muscle stem cell therapy in humans.

The interdisciplinary, cross-laboratory collaboration between Zon, Wagers, and Kahn highlights the advantage of open exchange between researchers. "If we had done this screen directly on human iPS cells, it would have taken at least 10 times as long and cost 100 times as much," said Wagers. "The zebrafish gave us a big advantage here because it has a fast generation time, rapid development, and can be easily and relatively cheaply screened in a culture dish."

"This research demonstrates that over 300 million years of evolution, the pathways used in the fish are conserved through vertebrates all the way up to the human," said Wagers' fellow HSCRB professor Leonard Zon, chair of the Harvard Stem Cell Institute Executive Committee and director of the stem cell program at Boston Children's Hospital. "We can now make enough human muscle progenitors in a dish to allow us to model diseases of the muscle lineage, like Duchenne muscular dystrophy, conduct drug screens to find chemicals that correct those disease, and in the long term, efficiently transplant muscle stem cells into a patient."

In a similar biomedical application, Kahn, who is chief academic officer at the Joslin, plans to apply the new ability to quickly produce muscle stem cells for diabetes research. His lab will generate iPS-derived muscle cells from people who are at risk for diabetes and people who have diabetes to identify alterations that lead to insulin resistance in the muscle.

Originally posted here:
Human muscle stem cell therapy gets help from zebrafish

There have been hundreds of science fiction stories and books written about growing organs in scientific laboratories as replacements for those that no longer function properly, or about injecting scientifically transmuted cells into ailing patients that can repair the broken cells within their bodies, bringing them back to robust health. In todays language what they were talking about was Induced Pluripotent Stem Cell (iPSC) Therapy.

Here, in the early 21st century, the gap between science fiction and science truth is closing at a record rate due to the rapid progress made in iPSC Therapy research, especially over the last three years.

After the virtual stop order placed on embryonic cell stem research in 2001, the race to find an alternative type of stem cell began in earnest, and in 2006 Shinya Yamanaka of Kyoto University in Japan announced his teams successful reprogramming of mouse cells into iPSCs. This was the breakthrough that made it possible for stem cell research to continue without the use of controversial embryonic stem cells.

The next major announcement came in 2007, again from Yamanaka in Japan, followed by one only a few weeks later by James A. Thompson from the University of Wisconsin, detailing the making of iPSC from adult human cells. Again, neither used embryos in their experiments.

From that time on the goal has been developing stem cell science that will eventually be safe iPS Cell Therapy modalities to be used in Regenerative or Reparative Medicine. What kinds of illnesses or diseases will iPSC Therapies be used to treat in the future? Only a partial list would include:

The world of iPSC Therapy research is wide open today and its on the move! This website is dedicated to bringing you first, the story of stem cell research, both embryonic and iPStem Cell, and the controversy surrounding them, as well as the most up to date information in the easiest to understand language about major milestone accomplishments in the field.

If you were to go back 100 years you would be amazed by how primitive medicine was. Even 60 years ago there were no organ transplants, no cystoscopic surgeries, and there was a massive polio outbreak in the United States that closed public swimming pools and beaches and other public gathering places across the country for the summer. Who can tell where medicine will be in 10 or 15 years? There is no predicting, but with the rapid advancement of the last few years and the bright promise shown so far, iPSC Therapy is sure to play a major role.

Continued here:
iPSCTherapy.com: Induced Pluripotent Stem Cell therapy Information ...

T he International Cellular Medicine Society (ICMS) is an international non-profit dedicated to patient safety through strict evaluation of protocols and rigorous oversight of clinics and facilities engaged in the translation of point-of-care cell-based treatments.As a Professional Medical Association, the ICMS represents Physiciansand Researchersfrom over 35 countries who share a mission to provide Scientifically Credible and Medically Appropriate Treatments to Informed Patients.Join the ICMS.

The ICMS Works Tirelessly for the Clincial Translation of Field of Cell-Based Point-of-Care Treatments through:

Comprehensive Medical Standards and Best Practice Guidelines for Cell Based Medicine,

Strict Evaluation and Rigerous Oversight of Stem Cell Clinics and Facilities through aGlobal Accreditation Process,

Physician Education through daily updates on the latest Research on Stem Cells, the monthly Currents In Stem Cell Medicine and the annual International Congress for Regenerative and Stem Cell Medicine.

Join the ICMSto receive the latest news and research from cell-based medicne, including the bi-monthly publication, Currents in Stem Cell Medicine.

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Stem Cells | ICMS -- Advancing Stem Cell Treatments, Stem Cell ...

Stem cells are the building blocks of your skin. They have a unique ability to replace damaged and diseased cells. As they divide, they can proliferate for long periods into millions of new skin cells.

As we age, our stem cells lose their potency. Your skins ability to repair itself just isnt what it used to be. The result can be fine lines, wrinkles, age spots, and sagging skin. But non-embryonic stem cells the same stem cells active early in life are highly potent.

Emerge Skin Cares Anti-Aging Stem Cell Skin Care Serum tap into the potency of these stem cells to renew skin.

Scientists at Emerge Labs Stem Cell Skin Care discovered that human non-embryonic stem cell extracts can renew skin by replacing old cells with healthy new ones. These stem cell extracts stimulate your own skins abilities to repair itself. And Emerge anti-aging stem cell serums were born. Where Stem Cells in Anti Aging Products Come From The first types of human stem cells to be studied by researchers were embryonic stem cells, donated from in vitro fertilization labs. But because creating embryonic stem cells involves the destruction of a fertilized human embryo, many people have ethical concerns about the use of such cells.

The non-embryonic stem cells in Lifeline stem cell serums are derived from unfertilized human oocytes (eggs) which are donated to ISCO from in vitro fertilization labs and clinics. Emerge Anti Aging Stem Cell Skin Care is Based On Proven Scientific Research Emerge Skin Cares exclusive anti-aging products are a combination of several discoveries and unique high-technology, patent-pending formulations.

PhytoCellTecMalus Domestica the first plant stem cell activefor skin stem cell protection with proven efficacy PhytoCellTec Malus Domestica is a liposomal preparation of apple stem cells developed by a novel, patent pending plant cell culture technology.

PhytoCellTec a novel plant cell culture technology has been invented to cultivate dedifferentiated callus cells from a rare Swiss apple. These apple stem cells are rich in epigenetic factors and metabolites, assuring the longevity of skin cells. PhytoCellTec Malus Domestica has been shown to protect skin stem cells and delay the senescence of hair follicles.

PhytoCellTec Malus Domestica provides a revolutionary anti-aging performance for real rejuvenation.

Claims with PhytoCellTec Malus Domestica Protects longevity of skin stem cells Delays senescence of essential cells Combats chronological aging

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Stem Cell Skin Care - Science Meets Beauty

Do Years Of Experience Show On Your Face?

Get FACELIFT results with an anti-aging cream!

You want to look your best, and looking your best means doing what you can do to reduce the signs of aging. Many of the women I know would have a face lift in a second if they didn't have to have surgery to get it. When you consider the drawbacks to face lift surgery the expense, recovery time, threat of infection or scarring, and stories of botched operations just to name a few, it is hard for many people to justify the procedure for themselves.

Up until now your options were limited. You could have botox, but botox actually paralyzes the muscles, and comes with its own set of risk factors. Then you have to have it done over and over again, exposing yourself to more expense and risk each time. The only other viable option was to try one of the many many skin creams on the market that often promise fantastic results but fail to deliver.

Stem cells are cells that have the ability to grow into any kind of cell in the body, and they rely on special signals to tell them what cells they will ultimately become. If you know the stem cell language, then you could communicate to the cells.

In this way, you could have stem cells that become new young skin cells, rebuild collagen, and deliver a new younger looking skin.

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LUMINESCE Stem Cell Skin Care

The First Tissue-Engineered Airway Transplantation: 5-Year Follow-Up Results In 2008, the first transplantation of a tissue-engineered trachea in a human being was done to replace an end-staged left main bronchus with malacia in a 30-year-old woman. Researchers report five year follow-up results. [Lancet] Abstract

Resident Neural Stem Cells Restrict Tissue Damage and Neuronal Loss after Spinal Cord Injury in MiceCentral nervous system injuries are accompanied by scar formation. It has been difficult to delineate the precise role of the scar, as it is made by several different cell types, which may limit the damage but also inhibit axonal regrowth. Scientists showed that scarring by neural stem cell-derived astrocytes is required to restrict secondary enlargement of the lesion and further axonal loss after spinal cord injury. [Science] Abstract| Press Release

iPSC-Derived Neural Precursors Exert a Neuroprotective Role in Immune-Mediated Demyelination via the Secretion of LIF Scientists showed that mouse induced pluripotent stem cell (iPSC)-derived neural stem/precursor cells - when intrathecally transplanted after disease onset - ameliorate clinical and pathological features of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. [Nat Commun] Abstract

The Enhancement of Bone Regeneration by Gene Activated Matrix Encoding for Platelet Derived Growth FactorResearchers developed and tested a non-viral gene delivery system for bone regeneration utilizing a collagen scaffold to deliver polyethylenimine-plasmid DNA (encoding platelet derived growth factor-B) complexes. [Biomaterials] Abstract

Interferon-?-Secreting Mesenchymal Stem Cells Exert Potent Antitumor Effect In VivoScientists tested whether mesenchymal stem cells continuingly secreting interferon-? (IFN?) can exert a persistent antitumor effect and eliminate the side effects associated with high clinical doses of recombinant IFN?. [Oncogene] Abstract

Mesenchymal Stem Cell Therapy Induces Glucocorticoid Synthesis in Colonic Mucosa and Suppresses Radiation-Activated T Cells: New Insights into MSC Immunomodulation In a rat model of radiation proctitis, investigators evidenced that a single mesenchymal stem cell (MSC) injection reduces colonic mucosa damages induced by ionizing radiation with improvement of the re-epithelization process for up to 21 days. [Mucosal Immunol] Abstract

Production and First-in-Man Use of T Cells Engineered to Express a HSVTK-CD34 Sort-Suicide GeneSuicide gene modified donor T cells can improve immune reconstitution after allogeneic hematopoietic stem cell transplantation, but can be eliminated in the event of graft versus host disease through the administration of prodrug. Researchers report the production and first-in-man use of mismatched donor T cells modified with a gamma-retroviral vector expressing a herpes simplex thymidine kinase (HSVTK):truncated CD34 suicide gene/magnetic selection marker protein. [PLoS One] Full Article| Press Release

The Therapeutic Effects of Human Adipose-Derived Stem Cells in Alzheimer's Disease Mouse ModelsIntravenously or intracerebrally transplanted human adipose-derived stem cells (hASCs) greatly improved memory impairment and neuropathology, suggesting that hASCs have a high therapeutic potential for Alzheimer's disease. [Neurodegener Dis] Abstract

Safety of Human Neural Stem Cell Transplantation in Chronic Spinal Cord InjuryResearchers assessed safety parameters for delayed transplantation of human central nervous system-derived neural stem cells (hCNS-SCns) by comparing hCNS-SCns transplantation in the subacute period, 9 days postinjury (DPI), versus the chronic period, 60 DPI, in contusion-injured athymic nude rats. [Stem Cell Transl Med] Abstract| Press Release

REVIEWS

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CellTherapyNews — Cell Therapy News Home

Adult Stem Cells Enhancer, From Fermented Biotechnology.
Consistently Increase of 50-100% Bone Marrow stem cells. This is most powerful Stem Cell Enhancer Consistently Increase 50-100%, From Fermented Biotechnology...

By: Adam Kee

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Adult Stem Cells Enhancer, From Fermented Biotechnology. - Video

PURTIER Placenta Live Stem Cell Therapy (ENGLISH)
If you have other enquiries, please contact us at +65 8200 8227 Email: TrueStemCell@gmail.com PURTIER Placenta Live Stem Cell Therapy has been effective for the following conditions: General...

By: Kim Purtier Placenta

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PURTIER Placenta Live Stem Cell Therapy (ENGLISH) - Video

When injury occurs to the spinal cord, the connections between the brain and the body are hampered or broken, which results in some level of impairment and a certain degree of paralysis. Symptoms may include movement disability, loss of sensation, impaired control of urination and defecation, cramps, pain and depression.

Conventional treatments for spinal cord injury are focused on prevention of secondary damage and providing rehabilitation.

Background information on this condition

With the advancement of stem cell treatments in China now you have a novel treatment option for Spinal Cord Injury. Stem cell therapy can support the natural regeneration processes of the body by stimulating the repair of damaged tissues. It goes beyond symptomatic treatment and may potentially help you to improve or regain some of the impaired functions.

Cell death occurs when cells are injured. However, these dead cells are surrounded by damaged and healthy cells. Stem cells have the potential to stimulate the healing of these injured cells by the secretion of cytokines, such as nerve growth factor to promote the bodys self-repair mechanisms.

Stem cells are injected by an innovative procedure known as a CT-guided intraspinal injection technique and this is supplemented by further stem cell transplantation via lumbar punctures or IV injections.

We are proud to be the pioneers of the CT-guided intraspinal stem cell transplantation surgical procedure, which is a landmark in the field of stem cell therapy for Spinal Cord Injury. To date, CT-guided intraspinal stem cell transplantation is only available at our hospital in China. CT guidance enables the neurosurgeon to target the stem cells precisely, administering the stem cells inside healthy spinal cord tissue adjacent to the lesion. This technique avoids open surgery of the spine. Thus pain, risks, and healing time are all minimized.

Our doctors understand that a variety of factors may influence decisions regarding your treatment. Our team is dedicated to patient education and collaboration so that you are clearly aware of your condition and treatment options. The hospital offers a wide range of treatments and related services. Therefore we advise you to consult with one of our specialists for personalized treatment information before you arrive to China.

We also encourage you to carefully study our CT Guided Transplantation Method and our stem cell treatment schedule.

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Stem Cell Treatment for Spinal Cord Injury (SCI) with CT Guidance

Stem cell transplants -- from bone marrow or other sources -- can be an effective treatment for people with certain forms of cancer, such as leukemia and lymphoma. Stem cell transplants are also used for multiple myeloma and neuroblastoma, and theyre being studied as a treatment for other cancers, too.

Why do cancer patients consider these transplants? While high doses of chemotherapy and radiation can effectively kill cancer cells, they have an unwanted side effect: They can also destroy the bone marrow, where blood cells are made.

Overview

Approximately 1.5 million new cases of cancer were expected to be diagnosed in the United States in 2009,[1] and that number is expected to rise in 2010.[2] Many patients diagnosed with cancer will eventually require support from a family caregiver. In fact, family caregivers form the foundation of the health care system in the United States, supporting advances in treatment such as multimodality treatment protocols given in outpatient and home settings.[3] Definition: Who Is the Caregiver? Also...

Read the Overview article > >

The purpose of a stem cell transplant or a bone marrow transplant is to replenish the body with healthy cells and bone marrow when chemotherapy and radiation are finished. After a successful transplant, the bone marrow will start to produce new blood cells. In some cases, the transplant can have an added benefit; the new blood cells will also attack and destroy any cancer cells that survived the initial treatment.

While you may have heard about embryonic stem cells in the news, the stem cells used in cancer treatment are different. Theyre called hematopoietic stem cells.

Whats special about these cells? Unlike most cells, these stem cells have the ability to divide and form new and different kinds of blood cells. Specifically, they can create oxygen-carrying red blood cells, infection-fighting white blood cells, and clot-forming platelets.

Most stem cells are in the bone marrow, a spongy tissue inside bone. Other stem cells -- called peripheral blood stem cells -- circulate in the blood. Both types can be used in stem cell transplants for cancer treatment.

While stem cell transplants may be lifesaving, theyre not the right treatment for everyone. The process can be difficult and tedious. Since younger people often do better with these treatments, some doctors limit stem cell transplants to those under age 60 or 70.

See more here:
Bone Marrow Transplants and Stem Cell Transplants for Cancer Treatment

05/15/13Portland, Ore.

The breakthrough marks the first time human stem cells have been produced via nuclear transfer and follows several unsuccessful attempts by research groups worldwide

Scientists at Oregon Health & Science University and the Oregon National Primate Research Center (ONPRC) have successfully reprogrammed human skin cells to become embryonic stem cells capable of transforming into any other cell type in the body. It is believed that stem cell therapies hold the promise of replacing cells damaged through injury or illness. Diseases or conditions that might be treated through stem cell therapy include Parkinsons disease, multiple sclerosis, cardiac disease and spinal cord injuries.

The research breakthrough, led by Shoukhrat Mitalipov, Ph.D., a senior scientist at ONPRC, follows previous success in transforming monkey skin cells into embryonic stem cells in 2007. This latest research will be published in the journal Cell online May 15 and in print June 6.

The technique used by Drs. Mitalipov, Paula Amato, M.D., and their colleagues in OHSUs Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynecology, is a variation of a commonly used method called somatic cell nuclear transfer, or SCNT. It involves transplanting the nucleus of one cell, containing an individuals DNA, into an egg cell that has had its genetic material removed. The unfertilized egg cell then develops and eventually produces stem cells.

A thorough examination of the stem cells derived through this technique demonstrated their ability to convert just like normal embryonic stem cells, into several different cell types, including nerve cells, liver cells and heart cells. Furthermore, because these reprogrammed cells can be generated with nuclear genetic material from a patient, there is no concern of transplant rejection, explained Dr. Mitalipov. While there is much work to be done in developing safe and effective stem cell treatments, we believe this is a significant step forward in developing the cells that could be used in regenerative medicine.

Another noteworthy aspect of this research is that it does not involve the use of fertilized embryos, a topic that has been the source of a significant ethical debate.

The Mitalipov teams success in reprogramming human skin cells came through a series of studies in both human and monkey cells. Previous unsuccessful attempts by several labs showed that human egg cells appear to be more fragile than eggs from other species. Therefore, known reprogramming methods stalled before stem cells were produced.

To solve this problem, the OHSU group studied various alternative approaches first developed in monkey cells and then applied to human cells. Through moving findings between monkey cells and human cells, the researchers were able to develop a successful method.

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OHSU research team successfully converts human skin cells into ...

Stem Cells and Spinal Cord Injury:

Spinal cord injuries are described at various levels of "incomplete", which can vary from having no effect on the patient to a "complete" injury which means a total loss of function.

Treatment of spinal cord injuries starts with restraining the spine and controlling inflammation to prevent further damage. The actual treatment can vary widely depending on the location and extent of the injury. In many cases, spinal cord injuries require substantial physical therapy and rehabilitation, especially if the patient's injury interferes with activities of daily life.

After a spinal cord injury, many of the nerve fibers at the injury site lose their insulating layer of myelin. As a result, the fibers are no longer able to properly transmit signals between the brain and the spinal cord contributing to paralysis. Unfortunately, the spinal cord lacks the ability to restore these lost myelin-forming cells after trauma.

Tissue engineering in the spinal cord involves the implantation of scaffold material to guide cell placement and foster cell development. These scaffolds can also be used to deliver stem cells at the site of injury and maximize their regenerative potential.

When the spinal cord is damagedeither accidentally (car accidents, falls) or as the result of a disease (multiple sclerosis, infections, tumors, severe forms of spinal bifida, etc.)it can result in the loss of sensation and mobility and even in complete paralysis.

Spinal Cord Injury and Stem Cell Treatment

Adult stem cell transplants for spinal cord injury repair: current state in preclinical research.

Hernndeza J, Torres-Espna A, Navarro X.

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Spinal Cord Injury Stem Cell Treatment - ASCI - Stem Cell Rejuvenation

The Promise of Stem Cells

Studying stem cells will help us understand how they transform into the dazzling array of specialized cells that make us what we are. Some of the most serious medical conditions, such as cancer and birth defects, are due to problems that occur somewhere in this process. A better understanding of normal cell development will allow us to understand and perhaps correct the errors that cause these medical conditions.

Another potential application of stem cells is making cells and tissues for medical therapies. Today, donated organs and tissues are often used to replace those that are diseased or destroyed. Unfortunately, the number of people needing a transplant far exceeds the number of organs available for transplantation. Pluripotent stem cells offer the possibility of a renewable source of replacement cells and tissues to treat a myriad of diseases, conditions, and disabilities including Parkinson's disease, amyotrophic lateral sclerosis, spinal cord injury, burns, heart disease, diabetes, and arthritis.

Scientists have been able to do experiments with human embryonic stem cells (hESC) since 1998, when a group led by Dr. James Thomson at the University of Wisconsin developed a technique to isolate and grow the cells. Although hESCs are thought to offer potential cures and therapies for many devastating diseases, research using them is still in its basic stages. hESCs are thought to offer potential cures and therapies for many devastating diseases, and we are now seeing the first clinical trials using cells derived from hESCs.

The NIH funded its first basic research study on hESCs in 2002. Since that time, biotechnology companies have built upon those basic foundations to begin developing stem cell-based human therapies. There are currently two active clinical trials using cells derived from human embryonic stem cells, both being conducted by a biotechnology company called ACT. The company has laboratories in Marlborough, Massachusetts and corporate offices in Santa Monica, California. ACT has begun enrolling patients for Phase I (safety and tolerability) clinical trials of two hESC-derived stem cell products:

In January, 2012, the investigators published a preliminary report on the first two patients treated with hESC-derived cells: http://www.ncbi.nlm.nih.gov/pubmed/22281388. A third patient was treated on April 20, 2012.

Late in 2007, scientists reported that they had been able to reprogram adult human skin cells to behave like hESCs. This type of stem cells is known as induced pluripotent stem cells, or iPSCs. Since these first reports, researchers have rapidly improved the techniques to generate iPSCs, creating a powerful new way to "de-differentiate" cells whose developmental fates were thought to be determined. In July 2013, Japans health minister approved the first clinical trial using cells derived from iPSCs. Masayo Takahashiin Kobe, Japan will use the cells to attempt to treat a form of blindness - age-related macular degeneration.

Bone marrow contains blood-forming stem cells (hematopoietic stem cells) that have been used for decades to treat blood cancers and other blood disorders. Umbilical cord blood is another source of hematopoietic stem cells that is being used in treatment. You can see a list of diseases that may currently be treated with hematopoietic stem cells at the website of the National Marrow Donor Program. You may also search for clinical trials testing "bone marrow stem cells" or "umbilical cord blood" on the ClinicalTrials.gov website.

A biotechnology company called Neuralstem (corporate headquarters in Rockville, Maryland) is conducting a clinical trial testing the use of human spinal cord stem cells to treat Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrigs Disease. The company obtained FDA approval to conduct a Phase I trial (safety and tolerability study) and began enrolling patients in January 2010. Twelve participants have received lumbar transplants, and in March 2012, the second participant received an injection in the cervial region. Details about this trial are listed on the ClinicalTrials.gov website.

Osiris Therapeutics (Columbia, Maryland) is conducting three different Phase 2 clinical trials with a product from adult mesenchymal cells (called Prochymal). The three trials are for:

See the article here:
Stem Cells and Diseases [Stem Cell Information]

CIRM funds a variety of research projects focused on finding a treatment for people with spinal cord injury. These projects range from basic work understanding how nerve cells are damaged in these injuries to projects trying move therapies into clinical trials.

If you want to learn more about CIRM funding decisions or make a comment directly to our board, join us at a public meeting. You can find agendas for upcoming public meetings on our meetings page.

Learn more about stem cell research: Stem Cell Basics Primer | Stem Cell Videos | What We Fund

Find clinical trials: CIRM does not track stem cell clinical trials. If you or a family member is interested in participating in a clinical trial, please see the national trial database to find a trial near you: clinicaltrials.gov

About 250,000 people in the U.S. live with spinal cord injuries. Half of those are quadriplegic, with the paralysis impacting all four limbs to some extent. For those individuals the lifetime cost of managing their condition is estimated to be between $2 million and $3 million.

Spinal cord injury became the first condition targeted in a human clinical trial using cells made from embryonic stem cells. That trial, begun by Geron in 2010 and based on the findings of a team CIRM currently funds, was later cancelled by Geron for financial reasons. By the time of the cancellation five patients around the country had been enrolled in the study, including two at Stanford, who entered the trial during a period when CIRM funded Geron. Those patients continue to be followed to learn as much as possible about this approach.

Californias stem cell agency retains many grants for research to move potential spinal cord injury therapies forward (the full list is below). Much of this work focuses on trying to determine which type of nerve cell is the best one to transplant, and deciding which type of stem cell is the best starting point for making those cells. Other research is trying to see if these transplanted cells become part of the existing nerve system, helping create new pathways that can transmit nerve signals to muscles. The researchers are also looking at ways to try and improve the ability of these transplanted cells to become part of the nerve system.

One obstacle that some teams are trying to overcome is the tendency of the scar at the site of injury to block the growth of these transplanted cells. One group is trying to overcome that by combining stem cells with synthetic scaffolds that can be placed at the site of injury, to help the cells bridge the scar and restore signals. In animal models this combination has resulted in an increase in mobility compared to stem cell grafts alone.

Progress and Promise toward a stem cell-based therapy for spinal cord injury

Total:

See more here:
Spinal Cord Injury Fact Sheet | California's Stem Cell Agency

This article is about the medical therapy. For the cell type, see Stem cell.

Stem cell therapy is an intervention strategy that introduces new adult stem cells into damaged tissue in order to treat disease or injury. Many medical researchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering.[1] The ability of stem cells to self-renew and give rise to subsequent generations with variable degrees of differentiation capacities,[2] offers significant potential for generation of tissues that can potentially replace diseased and damaged areas in the body, with minimal risk of rejection and side effects.

A number of stem cell therapies exist, but most are at experimental stages, costly or controversial,[3] with the notable exception of bone-marrow transplantation.[citation needed] Medical researchers anticipate that adult and embryonic stem cells will soon be able to treat cancer, Type 1 diabetes mellitus, Parkinson's disease, Huntington's disease, Celiac disease, cardiac failure, muscle damage and neurological disorders, and many others.[4] Nevertheless, before stem cell therapeutics can be applied in the clinical setting, more research is necessary to understand stem cell behavior upon transplantation as well as the mechanisms of stem cell interaction with the diseased/injured microenvironment.[4]

For over 30 years, bone-marrow, and more recently, umbilical-cord blood stem cells, have been used to treat cancer patients with conditions such as leukemia and lymphoma.[5][6] During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukaemia or neoplastic cells, and the hematopoietic stem cells within the bone marrow. It is this side effect of conventional chemotherapy strategies that the stem cell transplant attempts to reverse; a donor's healthy bone marrow reintroduces functional stem cells to replace the cells lost in the host's body during treatment.

Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. Healthy adult brains contain neural stem cells which divide to maintain general stem cell numbers, or become progenitor cells. In healthy adult animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). In pregnancy and after injury, this system appears to be regulated by growth factors and can increase the rate at which new brain matter is formed.[citation needed] Although the reparative process appears to initiate following trauma to the brain, substantial recovery is rarely observed in adults, suggesting a lack of robustness.[7]

Stem cells may also be used to treat brain degeneration, such as in Parkinson's and Alzheimer's disease.[8][9]

Pharmacological activation of an endogenous population of neural stem cells / neural precursor cells by soluble factors has been reported to induce powerful neuroprotection and behavioral recovery in adult rat models of neurological disorder through a signal transduction pathway involving the phosphorylation of STAT3 on the serine residue and subsequent Hes3 expression increase (STAT3-Ser/Hes3 Signaling Axis).[10][11][12]

Stem cell technology gives hope of effective treatment for a variety of malignant and non-malignant diseases through the rapid developing field that combines the efforts of cell biologists, geneticists and clinicians. Stem cells are defined as totipotent progenitor cells capable of self-renewal and multi-lineage differentiation. Stem cells survive well and show steady division in culture which then causes them the ideal targets for vitro manipulation. Research into solid tissue stem cells has not made the same progress as haematopoietic stem cells because of the difficulty of reproducing the necessary and precise 3D arrangements and tight cell-cell and cell-extracellular matrix interactions that exist in solid organs. Yet, the ability of tissue stem cells to assimilate into the tissue cytoarchitecture under the control of the host microenvironment and developmental cues, makes them ideal for cell replacement therapy. [3] [13]

The development of gene therapy strategies for treatment of intra-cranial tumours offers much promise, and has shown to be successful in the treatment of some dogs;[14] although research in this area is still at an early stage. Using conventional techniques, brain cancer is difficult to treat because it spreads so rapidly. Researchers at the Harvard Medical School transplanted human neural stem cells into the brain of rodents that received intracranial tumours. Within days, the cells migrated into the cancerous area and produced cytosine deaminase, an enzyme that converts a non-toxic pro-drug into a chemotheraputic agent. As a result, the injected substance was able to reduce the tumor mass by 81 percent. The stem cells neither differentiated nor turned tumorigenic.[15]

Some researchers believe that the key to finding a cure for cancer is to inhibit proliferation of cancer stem cells. Accordingly, current cancer treatments are designed to kill cancer cells. However, conventional chemotherapy treatments cannot discriminate between cancerous cells and others. Stem cell therapies may serve as potential treatments for cancer.[16] Research on treating lymphoma using adult stem cells is underway and has had human trials. Essentially, chemotherapy is used to completely destroy the patients own lymphocytes, and stem cells injected, eventually replacing the immune system of the patient with that of the healthy donor.

Read more here:
Stem cell therapy - Wikipedia, the free encyclopedia

Results from a ground-breaking Cedars-Sinai Heart Institute clinical trial show that an infusion of cardiac stem cells helps damaged hearts regrow healthy muscle.

The first-in-man clinical trial, based on technologies and discoveries made by Eduardo Marbn, MD, PhD, and led by Raj Makkar, MD, explored the safety of harvesting, growing and giving patients their own cardiac stem cells to repair heart tissue injured by heart attack.

The studys findings, published in The Lancet, show that heart attack patients who received stem cell treatment demonstrated a significant reduction in the size of the scar left on the heart muscle; this is a pioneering stem cell result, says Marban, who notes the study shows actual regeneration of tissues. With support from the California Institute for Regenerative Medicine, the Heart Institute team is now planning future clinical trials to treat advanced heart disease patients with stem cells.

The process to grow cardiac-derived stem cells involved in the study was developed earlier by Marbn when he was on the faculty of Johns Hopkins University. The university has filed for a patent on that intellectual property, and has licensed it to a company in which Marbn has a financial interest. No funds from that company were used to support the clinical study. All funding was derived from the National Institutes of Health and Cedars-Sinai Medical Center.

Since the Cedars-Sinai team completed the worlds first cardiac stem cell infusion in 2009, additional insights have emerged from this and related work, including the discovery in animals that iron-infused cardiac stem cells can be guided with a magnet to damaged areas of the heart, dramatically increasing their retention and healing potential.

Another finding to emerge from Marbns cardiac stem cell lab may have implications for many peoples health: Stem cells exposed to high doses of supplemental antioxidants can develop genetic abnormalities that predispose them to cancer formation.

Click here to watch a CBS Evening News story about the clinical trials results.

More here:
Cardiac Stem Cell Research - Cedars-Sinai

Heart attacks and congestive heart failure remain among the Nation's most prominent health challenges despite many breakthroughs in cardiovascular medicine. In fact, despite successful approaches to prevent or limit cardiovascular disease, the restoration of function to the damaged heart remains a formidable challenge. Recent research is providing early evidence that adult and embryonic stem cells may be able to replace damaged heart muscle cells and establish new blood vessels to supply them. Discussed here are some of the recent discoveries that feature stem cell replacement and muscle regeneration strategies for repairing the damaged heart.

For those suffering from common, but deadly, heart diseases, stem cell biology represents a new medical frontier. Researchers are working toward using stem cells to replace damaged heart cells and literally restore cardiac function.

Today in the United States, congestive heart failurethe ineffective pumping of the heart caused by the loss or dysfunction of heart muscle cellsafflicts 4.8 million people, with 400,000 new cases each year. One of the major contributors to the development of this condition is a heart attack, known medically as a myocardial infarction, which occurs in nearly 1.1 million Americans each year. It is easy to recognize that impairments of the heart and circulatory system represent a major cause of death and disability in the United States [5].

What leads to these devastating effects? The destruction of heart muscle cells, known as cardiomyocytes, can be the result of hypertension, chronic insufficiency in the blood supply to the heart muscle caused by coronary artery disease, or a heart attack, the sudden closing of a blood vessel supplying oxygen to the heart. Despite advances in surgical procedures, mechanical assistance devices, drug therapy, and organ transplantation, more than half of patients with congestive heart failure die within five years of initial diagnosis. Research has shown that therapies such as clot-busting medications can reestablish blood flow to the damaged regions of the heart and limit the death of cardiomyocytes. Researchers are now exploring ways to save additional lives by using replacement cells for dead or impaired cells so that the weakened heart muscle can regain its pumping power.

How might stem cells play a part in repairing the heart? To answer this question, researchers are building their knowledge base about how stem cells are directed to become specialized cells. One important type of cell that can be developed is the cardiomyocyte, the heart muscle cell that contracts to eject the blood out of the heart's main pumping chamber (the ventricle). Two other cell types are important to a properly functioning heart are the vascular endothelial cell, which forms the inner lining of new blood vessels, and the smooth muscle cell, which forms the wall of blood vessels. The heart has a large demand for blood flow, and these specialized cells are important for developing a new network of arteries to bring nutrients and oxygen to the cardiomyocytes after a heart has been damaged. The potential capability of both embryonic and adult stem cells to develop into these cells types in the damaged heart is now being explored as part of a strategy to restore heart function to people who have had heart attacks or have congestive heart failure. It is important that work with stem cells is not confused with recent reports that human cardiac myocytes may undergo cell division after myocardial infarction [1]. This work suggests that injured heart cells can shift from a quiescent state into active cell division. This is not different from the ability of a host of other cells in the body that begin to divide after injury. There is still no evidence that there are true stem cells in the heart which can proliferate and differentiate.

Researchers now know that under highly specific growth conditions in laboratory culture dishes, stem cells can be coaxed into developing as new cardiomyocytes and vascular endothelial cells. Scientists are interested in exploiting this ability to provide replacement tissue for the damaged heart. This approach has immense advantages over heart transplant, particularly in light of the paucity of donor hearts available to meet current transplantation needs.

What is the evidence that such an approach to restoring cardiac function might work? In the research laboratory, investigators often use a mouse or rat model of a heart attack to study new therapies (see Figure 9.1. Rodent Model of Myocardial Infarction). To create a heart attack in a mouse or rat, a ligature is placed around a major blood vessel serving the heart muscle, thereby depriving the cardiomyocytes of their oxygen and nutrient supplies. During the past year, researchers using such models have made several key discoveries that kindled interest in the application of adult stem cells to heart muscle repair in animal models of heart disease.

Figure 9.1. Rodent Model of Myocardial Infarction.

( 2001 Terese Winslow, Lydia Kibiuk)

Recently, Orlic and colleagues [9] reported on an experimental application of hematopoietic stem cells for the regeneration of the tissues in the heart. In this study, a heart attack was induced in mice by tying off a major blood vessel, the left main coronary artery. Through the identification of unique cellular surface markers, the investigators then isolated a select group of adult primitive bone marrow cells with a high capacity to develop into cells of multiple types. When injected into the damaged wall of the ventricle, these cells led to the formation of new cardiomyocytes, vascular endothelium, and smooth muscle cells, thus generating de novo myocardium, including coronary arteries, arterioles, and capillaries. The newly formed myocardium occupied 68 percent of the damaged portion of the ventricle nine days after the bone marrow cells were transplanted, in effect replacing the dead myocardium with living, functioning tissue. The researchers found that mice that received the transplanted cells survived in greater numbers than mice with heart attacks that did not receive the mouse stem cells. Follow-up experiments are now being conducted to extend the posttransplantation analysis time to determine the longer-range effects of such therapy [8]. The partial repair of the damaged heart muscle suggests that the transplanted mouse hematopoietic stem cells responded to signals in the environment near the injured myocardium. The cells migrated to the damaged region of the ventricle, where they multiplied and became "specialized" cells that appeared to be cardiomyocytes.

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9. Can Stem Cells Repair a Damaged Heart? [Stem Cell Information]