Lack of Diversity in Embryonic Stem Cell Lines

Lack of Diversity in Embryonic Stem Cell Lines Monday, 21 December 2009 The most widely used human embryonic stem cell lines lack genetic diversity, a finding that raises social justice questions that must be addressed to ensure that all sectors of society benefit from stem cell advances, according to a University of Michigan research team. In the first published study of its kind, the U-M team analyzed 47 embryonic stem cell lines, including most of the lines commonly used by stem cell researchers. The scientists determined the genetic ancestry of each line and found that most were derived from donors of northern and western European ancestry. Several of the lines are of Middle Eastern or southern European ancestry. Two of the lines are of East Asian origin. None of the lines were derived from individuals of recent African ancestry, from Pacific Islanders, or from populations indigenous to the Americas. In addition, U-M researchers identified several instances in which more than one cell line came from the same embryo donors, further reducing the overall genetic diversity of the most widely available lines. "Embryonic stem cell research has the potential to change the future of medicine," said Sean Morrison, director of the U-M Center for Stem Cell Biology and one of the study leaders. "But there's a lack of diversity among today's most commonly used human embryonic stem cell lines, which highlights an important social justice issue." "We expected Europeans to be overrepresented, but we were surprised by how little diversity there is," he said. For the study, Morrison teamed up with two colleagues at the U-M Life Sciences Institute: stem cell scientist Jack Mosher and population geneticist Noah Rosenberg. Their findings are scheduled to be published online Wednesday in the New England Journal of Medicine. A fundamental principle of medical research is that new therapies are tested on patients that mirror the diversity in society, because certain groups may respond to medications and treatments differently. By evaluating new therapies in diverse patients, researchers are more likely to detect the different effects these therapies might have. Embryonic stem cell lines are being used to develop new cellular therapies for spinal cord injuries and various diseases, to screen for new drugs and to better understand inherited diseases. It is crucial that diverse lines are available for this research to ensure that all patients benefit from the results, Morrison said. "If that's not done, we run the risk of leaving certain groups in our society behind," said Morrison, who is a Howard Hughes Medical Institute investigator at U-M. The U-M report comes as Michigan researchers launch new projects made possible by a recent state constitutional amendment allowing researchers in the state to derive new human embryonic stem cell lines using approaches already used in the rest of the country. The Michigan initiatives are getting underway as stem cell scientists across the nation respond to sweeping policy changes issued by the Obama administration. On Dec. 2, the U.S. National Institutes of Health announced it had approved 13 new human embryonic stem cell lines for use by federally funded researchers. Since that announcement, 40 lines have been approved for federal funding, including 22 lines that were part of the U-M genotyping study. Estimates of the total number of human embryonic stem cell lines in the world range up to 700. "While there are likely other lines out there that come from populations not represented in our study, those are not the lines that are most widely distributed and employed in stem cell research," said Rosenberg, a research associate professor at LSI. In Michigan, U-M researchers announced on Dec. 8 that they received approval from the Medical School's Institutional Review Board and the university's Human Pluripotent Stem Cell Research Oversight Committee to begin accepting donated embryos that will be used to derive the university's first human embryonic stem cell lines. It is the first U-M project made possible by Proposal 2, the state constitutional amendment approved by Michigan voters in November 2008, easing restrictions on human embryonic stem cell research in the state. The derivation project will be conducted by the university's new Consortium for Stem Cell Therapies, which includes researchers from across campus, as well as collaborators at Michigan State University and Wayne State University. Project scientists expect to begin accepting the first donated embryos early next year and to achieve their first embryonic stem cell line by mid-2010. The work must abide by the restrictions imposed by the Michigan Constitution and federal regulations. A top priority for the consortium is to derive lines that carry the genes responsible for inherited diseases. Morrison, a member of the consortium's scientific advisory board, said the University of Michigan "will also make it a priority to derive new embryonic stem cell lines from underrepresented groups, including African-Americans." But progress could be undermined by a package of bills now before the Michigan Legislature, Morrison said. The bills seek to impose new restrictions on embryonic stem cell research that could block much of the research approved by voters under Proposal 2, he said. In the U-M study, Mosher extracted DNA from embryonic stem cells and identified the pattern of genetic variation at nearly 500,000 sites within the genome, a process called genotyping. Rosenberg then compared the stem-cell genotypes to databases containing genetic information from 2,001 individuals of known ancestry. "If we find that a stem cell line is very similar genetically to people from a certain population that has previously been studied, then that's good evidence that the embryonic stem cell line was derived from donors belonging to that population, or a closely related population," Rosenberg said. Mosher noted that the U-M Life Sciences Institute was created to bring together researchers with different sets of expertise to collaborate on problems they could not solve individually. "This is a perfect example of that type of cross-disciplinary collaboration," said Mosher, an assistant research scientist at LSI. "By combining two seemingly disparate scientific approaches, we were able to make a discovery that adds important new insights." ......... ZenMaster

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Successful Stem Cell Therapy for Treatment of Eye Disease

Successful Stem Cell Therapy for Treatment of Eye Disease Monday, 21 December 2009 Newly published research, by investigators, at the North East England Stem Cell Institute (NESCI) in the journal Stem Cells reported the first successful treatment of eight patients with "Limbal Stem Cell Deficiency" (LSCD) using the patients' own stem cells without the need of suppressing their immunity. LSCD is a painful, blinding disease that requires long-term, costly treatment with frequent clinic visits and intensive hospital admissions. The vision loss due to LSCD makes this disease not only costly, but often requires social support due to the enormous impact on patient's quality of life. This is further magnified by the fact that LSCD mostly affects young patients. Dr Francisco Figueiredo, a member of the NESCI team, said: "Corneal cloudiness has been estimated to cause blindness in 8 million people (10% of total blindness) worldwide each year. A large number of ocular surface diseases, both acquired and congenital, share features of partial or complete LSCD. " Chemical burns to the eye are the most common cause of LSCD. Professor Lako said: "This study demonstrates that transplantation of cultured corneal stem cells without the use of animal cells or products is a safe and effective method of reconstructing the corneal surface and restoring useful sight in patients with unilateral LSCD.” "This research shows promise to help hundreds of people regain their sight. These exciting results offer a new treatment and hope for people with LSCD." Professor Michael Whitaker FMedSci, Co-Director of NESCI, which is a collaboration between Durham and Newcastle Universities, Newcastle NHS Foundation Trust and other partners, said: "Stem cells from bone marrow have been used successfully for many years to treat cancer and immune disease, but this is the first successful stem cell therapy using stem cells from the eye without animal products to treat disease, an important step towards the clinic. Because the early results look so promising, we are thinking hard now about how to bring this treatment rapidly into the clinic as we complete the necessary clinical trials, so that the treatment can be shared with all patients that might benefit." "The Newcastle team has obtained some very impressive results in patients following stem cell transplants to repair the surface of the cornea. It is hugely exciting to see that a type of stem cell therapy can now be applied routinely to treat a form of blindness," said Professor Robin Ali, FMedSci, Department of Genetics, UCL Institute of Ophthalmology, London. "These results also provide us with further encouragement to develop stem cell therapies to repair the retina in order to treat conditions such as age related macular degeneration." A larger study involving 24 new patients is currently underway with funding from the UK's Medical Research Council. ......... ZenMaster

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Gene Therapy and Stem Cells save Limb

Gene Therapy and Stem Cells save Limb Wednesday, 09 December 2009 Blood vessel blockage, a common condition in old age or diabetes, leads to low blood flow and results in low oxygen, which can kill cells and tissues. Such blockages can require amputation resulting in loss of limbs. Now, using mice as their model, researchers at Johns Hopkins have developed therapies that increase blood flow, improve movement and decrease tissue death and the need for amputation. The findings, published online last week in the early edition of the Proceedings of the National Academy of Sciences, hold promise for developing clinical therapies. "In a young, healthy individual, hypoxia — low oxygen levels — triggers the body to make factors that help coordinate the growth of new blood vessels but this process doesn't work as well as we age," says Gregg Semenza, M.D., Ph.D., professor of paediatrics and genetic medicine and director of the vascular biology program at the Johns Hopkins Institute for Cell Engineering. "Now, with the help of gene therapy and stem cells we can help reactivate the body's response to hypoxia and save limbs." Previously, Semenza's team generated a virus that carries the gene encoding an active form of the HIF-1 protein, which turns on genes necessary for building new blood vessels. When injected into the hind legs of otherwise healthy mice and rabbits that had been treated to reduce blood flow, the HIF-1 virus treatment partially restored blood flow. People with diabetes have a 40 times higher risk of losing a limb to amputation, says Semenza. To find out if HIF-1 gene therapy could improve blood flow in a diabetic animal, the team then tested the same virus in diabetic and non-diabetic mice that had blood flow cut off to one hind leg. Twenty-one days after treatment, the HIF-1 virus-treated mice had 85 percent recovery of blood flow compared with 24 percent in the mock-treated mice. In addition, treated, diabetic mice had much less tissue damage compared to the untreated diabetic mice. These results were reported in the Nov. 3 issue of the Proceedings of the National Academy of Sciences. In the current study, the team asked if the same gene therapy treatment could improve reduced blood flow associated with advanced age. Comparing 13-month-old mice to 3-month-old mice, blocking the femoral artery in the hind leg causes all older mice to lose their legs while only about a third of younger mice have to lose their legs. The research team treated young and old mice with the HIF-1 virus and examined blood flow and tissue health. They found that while treatment improved young mice, it did not make a noticeable difference in the older mice. However, it was known that when HIF-1 normally activates signals in the body to build new vessels, one of the many types of cells recruited to the site of new vessel growth is a population of stem cells from the bone marrow, which are called bone marrow-derived angiogenic cells. Therefore, the team isolated these cells from mice and grew them under special conditions that would turn on HIF-1 in these cells. When the researchers treated the mice with both the HIF-1 virus and simultaneously injected bone marrow-derived angiogenic cells, treated, older mice were less likely to lose their legs compared to their untreated counterparts. Further study of these mice showed that activating HIF-1 in the cells appeared to turn on a number of genes that help these cells not only home to the ischemic limb, but to stay there once they arrive. To figure out how the cells stay where they're needed, the research team built a tiny micro-fluidic chamber and tested the cells' ability to stay stuck with fluid flowing around them at rates mimicking the flow of blood through vessels in the body. They found that cells under low oxygen conditions were better able to stay stuck only if those same cells had HIF-1 turned on. "Our results are promising because they show that a combination of gene and cell therapy can improve the outcome in the case of critical limb ischemia associated with aging or diabetes," says Semenza. "And that's critical for bringing such treatment to the clinic." ......... ZenMaster

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Umbilical Stem Cells May Help Recover Lost Vision for Those With Corneal Disease

Umbilical Stem Cells May Help Recover Lost Vision for Those With Corneal Disease Wednesday, 09 December 2009 New research from the University of Cincinnati (UC) may help in the recovery of lost vision for patients with corneal scarring. Winston Whei-Yang Kao, PhD, professor of ophthalmology, along with other researchers in UC's ophthalmology department found that transplanting human umbilical mesenchymal stem cells into mouse models that lack the protein lumican restored the transparency of cloudy and thin corneas. Mesenchymal stem cells are "multi-potent" stem cells that can differentiate into a variety of cell types. These findings are being presented Dec. 8 in San Diego at the 49th Annual Meeting of the American Society for Cell Biology. "Corneal transplantation is currently the only true cure for restoration of eyesight that may have been lost due to corneal scarring caused by infection, mechanical and chemical wounds and congenital defects of genetic mutations," Kao says. "However, the number of donated corneas suitable for transplantation is decreasing as the number of individuals receiving refractive surgeries, like LASIK, increases." "Worldwide, there is a shortage of suitable corneas for transplantation, and at the present time, there is no effective alternative procedure besides corneal transplantation to treat corneal blindness," he continues. "There is a large need to develop alternative treatment regimens, one of which may be the transplantation of mesenchymal stem cells." Researchers used mouse models that did not have the lumican gene, also known as lumican knock-out models. Lumican is a protein that controls the formation and maintenance of transparent corneas. "Lumican knock-out models manifested thin and cloudy corneas," he says. "Transplantation of the umbilical stem cells significantly improved transparency and increased corneal stromal thickness in these mice." In addition, Kao says, the umbilical mesenchymal stem cells survived in the mouse stroma (connective tissue) for more than three months with minimal or no rejection and became corneal cells, repairing lost functions caused by mutations. "Our results suggest a potential treatment regimen for congenital and/or acquired corneal diseases," he says, adding that the availability of human umbilical stem cells is almost unlimited. "These stem cells are easy to isolate and can be recovered quickly from storage when treating patients.” "These findings have the potential to create new and better treatments — and an improved quality of life — for patients with vision loss due to corneal injury." ......... ZenMaster

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Stem Cells and Acute Heart Attack

Researchers launch phase II clinical trial Wednesday, 09 December 2009 Researchers at The University of Texas Medical School at Houston have launched the second phase of a clinical trial testing a new stem-cell-based therapy on injured heart muscle. It is the only study site in the Texas Medical Center. Results from Phase I of the trial are published in today's issue of the Journal of the American College of Cardiology. Researchers reported that patients were treated safely with intravenous adult human mesenchymal stem cells (Prochymal) after a heart attack. In addition, they had fewer arrhythmias, improved heart and lung function, and improvement in overall condition. "We are able to use a stem cell product that is on the shelf without prior preparation of anything from the patient, and this product appears to be able to help the heart muscle recover after a heart attack," said Ali E. Denktas, M.D., the trial's Houston site principal investigator and assistant professor of cardiology at the UT Medical School at Houston. "This means patients have the potential to recover quicker with less risk of an immediate secondary attack." In many cell-based therapies, doctors harvest the patient's own cells, process them and then return them to the patient. Prochymal, developed by Osiris Therapeutics, Inc., contains adult mesenchymal stem cells from healthy donors. The cells can be stored at an emergency centre until needed. For purposes of the Phase II study, Prochymal must be administered within seven days of a heart attack. Yesterday, researchers enrolled the first patient for the Phase II study at the Houston site. Heart attack patient Melvin Dyess, 49, received an intravenous infusion of either the stem cells or placebo as part of the protocol of the double-blind study. The procedure took place at the Memorial Hermann Heart & Vascular Institute-Texas Medical Center. Denktas said UT Medical School researchers will continue to enrol willing patients into the Phase II study who are admitted to Memorial Hermann-Texas Medical Center. Neither patients nor their physicians know whether they received the stem cell drug. Affecting 1.1 million Americans every year, heart attacks are caused by disruptions to the heart's blood supply. Muscle cells can die within minutes of the blood being reduced or cut off. The body has a limited capacity to regenerate new heart muscles and repair wounds to the heart. Denktas said while cell-based therapies including Prochymal appear to work, researchers are not sure why. Previous studies have shown that adult stem cells have a "homing device" that sends them to the point of injury in the human body. "Studies with acute myocardial infarction (heart attack) show that if you give cells of some sort to the heart relatively quickly, five to 10 days after the heart attack, they nest themselves in the heart and the heart improve. But, why it improves is debatable," Denktas said. Adult mesenchymal stem cells appear to have anti-inflammatory, anti-fibrotic, and tissue regenerative capacities, as shown in both animal studies and human clinical trials, according to Osiris Therapeutics, Inc.. ......... ZenMaster

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Superior Offspring without Genetic Modification

Superior Offspring without Genetic Modification Tuesday, 08 December 2009 We don't always turn out like our parents. Sometimes we become even better. How this happens is the subject of a new research project at the University of Gothenburg. When two gene pools combine, you might expect the characteristics of the offspring to end up somewhere in the middle between those of its parents. But children often have characteristics that are better or worse than that middle value, sometimes even better than both parents. Better horses, redder tomatoes This is not a newly-recognized phenomenon. Indeed, it has been exploited to breed better horses, redder tomatoes, more nutritious rice, and salmon that can thrive in fish farms, to mention but a few examples. New research project Heterosis is the scientific term for being better than your parents. Why does heterosis occur? What is the molecular mechanism? How common is it? How can we make it happen more often and to greater effect? Researchers at the Department of Cell and Molecular Biology at the University of Gothenburg and the Norwegian University of Life Sciences outside Oslo are aiming to find answers to these questions in a new research project. Baker´s yeast Using baker's yeast as a model, Jonas Warringer and his colleague Stig Omholt are mapping the incidence of heterosis for a large number of different characteristics. They hope to discover the mechanisms in human cells that govern the creation of children with characteristics sometimes superior to those of their parents. They are initially studying yeast cells - in which the mechanism has already been established. Brewer’s yeast In their first studies, Warringer and Omholt have shown how heterosis has enabled brewer's yeast to develop tolerance to copper, something that helps the yeast to survive in the large copper tanks used in the brewing industry. After some of the results where published in Nature in March this year, the interest in Warringers and Omholts research has increased. Life on Mars "Once we understand how heterosis occurs, breeding can be controlled so that we can selectively promote desirable characteristics in plants and animals more quickly and effectively. This could help in the fight against famine, help us develop new bio fuels for cars, and possibly, in the distant future, make it possible to create a functioning ecosystem on Mars - without having to resort to genetic modification," says Jonas Warringer. ......... ZenMaster

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Stem Cells Can be Engineered to Kill HIV

Innovative strategy could be effective against other chronic viral diseases Tuesday, 08 December 2009 Researchers from the UCLA AIDS Institute and colleagues have for the first time demonstrated that human blood stem cells can be engineered into cells that can target and kill HIV-infected cells — a process that potentially could be used against a range of chronic viral diseases. The study, published Dec. 7 in the-peer reviewed online journal PLoS ONE, provides proof-of-principle — that is, a demonstration of feasibility — that human stem cells can be engineered into the equivalent of a genetic vaccine. "We have demonstrated in this proof-of-principle study that this type of approach can be used to engineer the human immune system, particularly the T-cell response, to specifically target HIV-infected cells," said lead investigator Scott G. Kitchen, assistant professor of medicine in the division of haematology and oncology at the David Geffen School of Medicine at UCLA and a member of the UCLA AIDS Institute. "These studies lay the foundation for further therapeutic development that involves restoring damaged or defective immune responses toward a variety of viruses that cause chronic disease, or even different types of tumours." Taking CD8 cytotoxic T lymphocytes — the "killer" T cells that help fight infection — from an HIV-infected individual, the researchers identified the molecule known as the T-cell receptor, which guides the T cell in recognizing and killing HIV-infected cells. These cells, while able to destroy HIV-infected cells, do not exist in enough quantities to clear the virus from the body. Therefore, the researchers cloned the receptor and genetically engineered human blood stem cells, then placed the stem cells into human thymus tissue that had been implanted in mice, allowing them to study the reaction in a living organism. The engineered stem cells developed into a large population of mature, multifunctional HIV-specific CD8 cells that could specifically target cells containing HIV proteins. The researchers also found that HIV-specific T-cell receptors have to be matched to an individual in much the same way that an organ is matched to a transplant patient. The next step is to test this strategy in a more advanced model to determine if it would work in the human body, said co-author Jerome A. Zack, UCLA professor of medicine in the division of haematology and oncology and associate director of the UCLA AIDS Institute. The researchers also hope to expand the range of viruses against which this approach could be used. However, the results of the study suggest that this strategy could be an effective weapon in the fight against AIDS and other viral diseases. "This approach could be used to combat a variety of chronic viral diseases," said Zack, who is also a professor of microbiology, immunology and molecular genetics. "It's like a genetic vaccine." ......... ZenMaster

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New Skin Stem Cells Surprisingly Similar to Those Found in Embryos

New Skin Stem Cells Surprisingly Similar to Those Found in Embryos Tuesday, 08 December 2009 Scientists have discovered a new type of stem cell in the skin that acts surprisingly like certain stem cells found in embryos: both can generate fat, bone, cartilage, and even nerve cells. These newly described dermal stem cells may one day prove useful for treating neurological disorders and persistent wounds, such as diabetic ulcers, says Freda Miller, an HHMI international research scholar. Miller and her colleagues first saw the cells several years ago in both rodents and people, but only now confirmed that the cells are stem cells. Like other stem cells, these cell scan self-renew and, under the right conditions, they can grow into the cell types that constitute the skin's dermal layer, which lies under the surface epidermal layer. "We showed that these cells are, in fact, the real thing," says Miller, a professor at the University of Toronto and a senior scientist in the department of developmental biology at the Hospital for Sick Children in Toronto. The dermal stem cells also appear to help form the basis for hair growth. The new work was published December 4, 2009, in the journal Cell Stem Cell. Though this research focuses on the skin, Miller has spent her career searching for cures for neurological diseases such as Parkinson's. About a decade ago, she decided to find an easily accessible cell that could be coaxed into making nerves. Brain stem cells, some of which can grow into nerves, lie deep in the middle of the organ and are too difficult to reach if the scientists eventually wanted to cultivate the cells from individual patients. "I thought, 'This is blue sky stuff, but you never know.'" She searched the literature and found that amphibians can regenerate nerves in their skin. She also found published "hints" that mammalian nerve cells could do the same. Her team looked in the dermal layer of the skin in both mice and people. Hair follicles and sweat glands are rooted in the dermis, a thick layer of cells that also help support and nourish blood vessels and touch-perceiving nerves. In 2001, Miller's team hit pay dirt when they discovered cells that respond to the same growth factors that make brain stem cells differentiate. She named them skin-derived precursors (SKPs, or 'skips'). Miller soon discovered that the cells act like neural crest cells from embryos — stem cells that generate the entire peripheral nervous system and part of the head — in that they could turn into nerves, fat, bone, and cartilage. "That gave us the idea that these were some kind of embryonic-like precursor cell that migrated into the skin of the embryo," Miller said. "But instead of disappearing as the embryo develops, the cells survive into adulthood." Even though the SKPs acted like stem cells in Petri dishes, Miller didn't know if they behaved the same way in the body. "We were obviously very excited about these cells," she said. "The problem was, cells can do all kinds of weird things in culture dishes that look right but really aren't. We thought, 'Maybe we're being deceived.'" So lab member Jeffrey Biernaskie put the cells through their paces, performing a series of experiments to test whether the SKPs indeed acted like stem cells in the body. Earlier work in the lab had shown that the SKPs produce a transcription factor called SOX2, which is produced in many types of stem cells. The team used genetically engineered mice with SOX2 genes tagged with green fluorescent protein, which allowed them to track where SOX2 was expressed in the animals. They found that about 1% of skin cells from adult mice contained the SOX2-making cells, and they were concentrated in the bulb at the base of hair follicles. When the team cultured these cells, they began behaving like SKPs. Next, the scientists decided to see if the cells would not just settle at the base of hair follicles but grow new hair. They took the fluorescent cells, mixed them with epidermal cells — that makes up the majority of cells in a hair follicle — and transplanted the mixture under the skin of hairless mice. These mice began growing hair, and analysis showed the green cells migrated to their "home base" in the bulb of the new hair follicles. The team also transplanted rat SKP cells under the skin of mice. The cells behaved exactly like dermal stem cells – they spread out through the dermis and differentiated into various dermal cell types, including fat cells and dermal fibroblasts, which form the structural framework of the dermal layer. Intriguingly, the mice that carried transplanted rat SKPs also grew longer, thicker, rat-like hair, instead of short, thin mouse hair. "These cells are instructive, they tell the epidermal cells – which form the bulk of the hair follicle – to make bigger, rat-like hair follicles," Miller said. "There are a lot of jokes in my lab about bald men running around with rat hair on their heads." Finally, the team gave mice small puncture wounds and then transplanted their fluorescent SKPs next to the wound. Within a month, many transplanted cells appeared in the scar, showing they had contributed to wound healing. The SKPs were also found in new hair follicles in the healed skin. The cells behaviour both in wound healing and hair growth led the team to conclude that the SKPs are, in fact, dermal stem cells. Miller said the finding complements work by HHMI investigator Elaine Fuchs, who found epidermal stem cells, which help renew the top layer of skin. Combining the evidence from the two labs suggests a possible path to baldness treatments, Miller said — the dermal stem cells at the base of the hair follicle seem to be signalling the epidermal cells that form the shaft of the follicle to grow hair. But much about the signalling mechanism remains unknown. Miller wants to investigate less cosmetic applications, such as treating nerve and brain diseases. Experiments she published between 2005 and 2007 showed that SKPs can grow into nerves and help repair spinal cord damage in rats. Her lab is continuing to pursue that research. She is also searching for signals that could trigger the dermal stem cells to rev up their innate wound-healing ability. If such a signal can be found and mimicked, Miller can envision one day treating chronic wounds – such as diabetic ulcers – with a topical cream. Such a treatment is years or decades away, she said, but now researchers know which cell types to focus on. Another possibility: improving skin grafts, which today consist of only epidermal, not dermal, cells. While skin grafts can dramatically help burn victims, those grafts don't function like normal skin. "Stem cell researchers like to talk about building organs in a dish," said Miller. "You can imagine, if you have all the right players – dermal stem cells and epidermal stem cells – working together, you could do that with skin in a very real way." Reference: SKPs Derive from Hair Follicle Precursors and Exhibit Properties of Adult Dermal Stem Cells Jeffrey Biernaskie, Maryline Paris, Olena Morozova, B. Matthew Fagan, Marco Marra, Larysa Pevny and Freda D. Miller Cell Stem Cell, Volume 5, Issue 6, 610-623, 4 December 2009, doi:10.1016/j.stem.2009.10.019 ......... ZenMaster

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Scientists Rescue Visual Function in Rats Using Induced Pluripotent Stem Cells

Scientists Rescue Visual Function in Rats Using Induced Pluripotent Stem Cells Friday, 04 December 2009 An international team of scientists has rescued visual function in laboratory rats with eye disease by using cells similar to embryonic stem cells. The research shows the potential for stem cell-based therapies to treat age-related macular degeneration in humans. A team led by Dennis Clegg, of UC Santa Barbara, and Pete Coffey, of University College London (UCL), published their work in two papers, including one published this week in the journal PLoS One. The first paper was published in the October 27 issue of the journal Stem Cells. The scientists worked with rats that have a mutation, which causes a defect in retinal pigmented epithelial (RPE) cells and leads to photoreceptor death and subsequent blindness. Human RPE cells were derived from induced pluripotent stem cells –– embryonic stem cell-like cells that can be made from virtually any cell in the body, thus avoiding the controversy involved in using stem cells derived from embryos. Pluripotent means that the cells can become almost any cell in the body. In experiments spearheaded by UCL's Amanda Carr, the team found that by surgically inserting stem cell-derived RPE into the retinas of the rats before photoreceptor degeneration, vision was retained. They found that the rats receiving the transplant tracked their visual focus in the direction of moving patterns more efficiently than control groups that did not receive a transplant. "Although much work remains to be done, we believe our results underscore the potential for stem-cell based therapies in the treatment of age-related macular degeneration," said Sherry Hikita, an author on both papers and director of UCSB's Laboratory for Stem Cell Biology. Dave Buchholz, first author of the article in Stem Cells, explained that by using induced stem cells that can be derived from patients, the scientists avoid immune rejection that might occur when using embryonic stem cells. "RPE cells are essential for visual function. Without RPE, the rod and cone photoreceptors die, resulting in blindness. This is the basic progression in age-related macular degeneration. The hope is that by transplanting fresh RPE, derived from induced pluripotent stem cells, the photoreceptors will stay healthy, preventing vision loss," according to Buchholz. References: Protective Effects of Human iPS-Derived Retinal Pigment Epithelium Cell Transplantation in the Retinal Dystrophic Rat Amanda-Jayne Carr, Anthony A. Vugler, Sherry T. Hikita, Jean M. Lawrence, Carlos Gias, Li Li Chen, David E. Buchholz, Ahmad Ahmado, Ma'ayan Semo, Matthew J. K. Smart, Shazeen Hasan, Lyndon da Cruz, Lincoln V. Johnson, Dennis O. Clegg, Pete J. Coffey PLoS ONE 4(12): e8152. doi:10.1371/journal.pone.0008152 Derivation of Functional Retinal Pigmented Epithelium from Induced Pluripotent Stem Cells David E. Buchholz, Sherry T. Hikita, Teisha J. Rowland, Amy M. Friedrich, Cassidy R. Hinman, Lincoln V. Johnson, Dennis O. Clegg STEM CELLS, Volume 27 Issue 10, DOI: 10.1002/stem.189 ......... ZenMaster

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Adult Stem Cells May Help Repair Hearts Damaged by Heart Attack

Rush University Medical Center enrolling patients for next phase of trial Thursday, 03 December 2009 Adult stem cells may help repair heart tissue damaged by heart attack according to the findings of a new study to be published in the December 8 issue of the Journal of the American College of Cardiology. Results from the Phase I study show stem cells from donor bone marrow appear to help heart attack patients recover better by growing new blood vessels to bring more oxygen to the heart. Rush University Medical Center was the only Illinois site and one of 10 cardiac centres across the country that participated in the 53-patient, double-blind, placebo-controlled Phase I trial. Rush is now currently enrolling patients for the second phase of the study. Researchers say it is the strongest evidence thus far indicating that adult stem cells can actually differentiate, or turn into heart cells to repair damage. Until now, it has been believed that only embryonic stem cells could differentiate into heart or other organ cells. "The results point to a promising new treatment for heart attack patients that could reduce mortality and lessen the need for heart transplants," said Dr. Gary Schaer, head of the Rush Cardiac Catheterization Laboratory and study principal investigator at Rush. In phase I of the study, a group of 53 patients who had heart attacks in the previous ten days received adult mesenchymal stem cells and were kept under close study for two years. The mesenchymal stem cells (MSC) were harvested from the bone marrow of healthy adult donors. These cells have the potential to develop into mature heart cells and new blood vessels. Similar to Blood Type O, mesenchymal stem cells have the advantage that they can be taken from the bone marrow of an unrelated donor without needing to be matched by blood type. After the stem cells were extracted, they were purified by drug manufacturer Osiris Therapeutics into a formulation for intravenous delivery called Prochymal. Patients were administered an infusion of either Prochymal or placebo as an injection into a vein in the arm or leg. To prevent bias, neither the patient nor the physician knew who received the stem cell treatment and who received the placebo. In the study, patients who received the adult stem cells were compared to similar patients who received inert placebo injections. MRI and echocardiogram followed both. After six months, patients who received the adult stem cells were four times as likely to have improved overall condition, were able to pump more blood with each heartbeat than untreated patients, had only one-quarter as many dangerous heart arrhythmias, and suffered no toxicity or other serious adverse side effects from the treatment. "It is suspected that these stem cells may take part in the growth of new blood vessels to bring more oxygen to the heart and help reduce the scarring from a heart attack," said Schaer. Echocardiograms showed patients had improved heart function, particularly in those patients with large amounts of cardiac damage. Patients also have improvements in lung function. According to Schaer, one reason the study results are so promising is that these stem cells can be used without tissue typing and do not trigger an immune response, and are available for every patient. A unique benefit of the stem cell product is that it is given to patients through a standard intravenous (IV) line which is simple and easy for the patient compared to other therapies that require delivery to the site of the disease through catheterization or open surgical procedures, Adult stem cells are designed by nature to perform tissue repair in a mature adult. It is believed that these cells can be used in patients unrelated to the donor, without rejection, eliminating the need for donor matching and recipient immune suppression. Once transplanted, the cells promote healing of damaged or diseased tissues. "It is possible that in the future, hospitals might be able to keep frozen adult stem cells on hand for speedy use in treating heart attacks," said Schaer. "This study suggests that adult bone marrow derived stem cells are more flexible than previously thought," said Schaer. "If the benefits and safety are confirmed in the ongoing Phase II trial, we may soon have a remarkable new therapy for patients with a large heart." ......... ZenMaster

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For more on stem cells and cloning, go to CellNEWS at http://cellnews-blog.blogspot.com/

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