Stem cells from muscle tissue may hold key to cell therapies for neurodegenerative diseases

Scientists at Wake Forest Baptist Medical Center have taken the first steps to create neural-like stem cells from muscle tissue in animals. Details of the work are published in two complementary studies published in the September online issues of the journals Experimental Cell Research and Stem Cell Research.

"Reversing brain degeneration and trauma lesions will depend on cell therapy, but we can't harvest neural stem cells from the brain or spinal cord without harming the donor," said Osvaldo Delbono, M.D., Ph.D., professor of internal medicine at Wake Forest Baptist and lead author of the studies.

"Skeletal muscle tissue, which makes up 50 percent of the body, is easily accessible and biopsies of muscle are relatively harmless to the donor, so we think it may be an alternative source of neural-like cells that potentially could be used to treat brain or spinal cord injury, neurodegenerative disorders, brain tumors and other diseases, although more studies are needed."

In an earlier study, the Wake Forest Baptist team isolated neural precursor cells derived from skeletal muscle of adult transgenic mice (PLOS One, Feb.3, 2011).

In the current research, the team isolated neural precursor cells from in vitro adult skeletal muscle of various species including non-human primates and aging mice, and showed that these cells not only survived in the brain, but also migrated to the area of the brain where neural stem cells originate.

Another issue the researchers investigated was whether these neural-like cells would form tumors, a characteristic of many types of stem cells. To test this, the team injected the cells below the skin and in the brains of mice, and after one month, no tumors were found.

"Right now, patients with glioblastomas or other brain tumors have very poor outcomes and relatively few treatment options," said Alexander Birbrair, a doctoral student in Delbono's lab and first author of these studies. "Because our cells survived and migrated in the brain, we may be able to use them as drug-delivery vehicles in the future, not only for brain tumors but also for other central nervous system diseases."

In addition, the Wake Forest Baptist team is now conducting research to determine if these neural-like cells also have the capability to become functioning neurons in the central nervous system.

Journal reference: PLoS ONE

Provided by Wake Forest University Baptist Medical Center

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Stem cells from muscle tissue may hold key to cell therapies for neurodegenerative diseases

Pioneering iPS Cell Scientist Kazutoshi Takahashi Receives NYSCF – Robertson Prize in Stem Cell Research

NEW YORK, Oct. 9, 2012 /PRNewswire/ --Today, The New York Stem Cell Foundation (NYSCF) will award a Japanese scientist with the NYSCF Robertson Prize for his extraordinary achievements in translational stem cell research.

This award will go to Kazutoshi Takahashi, PhD, Lecturer, Center for iPS Cell Research and Application (CiRA) at Kyoto University, for his vital contribution to induced pluripotent stem (iPS) cell derivation.

Dr. Takahashi was lead author on a series of landmark papers that described reprogramming adult cells into iPS cells, which were published while he was a postdoctoral researcher in Shinya Yamanaka's, MD, PhD, laboratory at Kyoto University.

Yesterday, judges in Stockholm announced that Dr. Yamanaka and Sir John Gurdon, DPhil, the Gurdon Institute, won the Nobel Prize in Physiology or Medicine for their stem cell research breakthroughs. Both scientists demonstrated that adult cells can be reprogrammed into pluripotent cells, cells that can become any cell type in the body.

The NYSCF Robertson prize will be presented at a ceremony in New York City by Susan L. Solomon, CEO of The New York Stem Cell Foundation, and Professor Peter J. Coffey, DPhil, the inaugural recipient of the NYSCF Robertson Prize in 2011, Executive Director of Translation at UC Santa Barbara's Center for Stem Cell Biology and Engineering, and Director of the London Project to Cure Blindness, University College London.

"Dr. Takahashi's path-breaking work truly has opened up the entire field of stem cell research," said Ms. Solomon. "In addition to his derivation of induced pluripotent stem cells, he focuses on improving this technique and other critical translational studies."

Dr. Takahashi's research group at Kyoto University was established in 2010 to focus on two areas of cellular reprogramming. Their first area of investigation is in the process of cellular reprogramming and the second area is evaluating iPS cell quality and differentiation potential.

"I congratulate Dr. Takahashi for his groundbreaking work, opening new avenues in the search for cures," said Julian H. Robertson, Jr. "The NYSCF Robertson Stem Cell Prize was created to recognize and support the work of young scientists like Dr. Takahashi, whose research offers enormous potential."

The jury that selected Dr. Takahashi in September consisted of Christine Mummery, PhD, Chair of the Department of Anatomy and Embryology at Leiden University Medical Center in the Netherlands; Lorenz Studer, MD, Director of the Sloan-Kettering Center for Stem Cell Biology; Irving Weissman, MD, Director of the Institute for Stem Cell Biology and Regenerative Medicine at the Stanford School of Medicine; and, Peter J. Coffey, DPhil.

The NYSCF Robertson prize is awarded annually to a young scientist in recognition of innovative and groundbreaking achievement, or body of work, that has significantly advanced human stem cell research toward clinical application. The terms of the prize require that the $200,000 stipend be used, at the recipients' discretion, to further support their research.

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Pioneering iPS Cell Scientist Kazutoshi Takahashi Receives NYSCF - Robertson Prize in Stem Cell Research

British, Japanese scientists share Nobel Prize for stem cell work

Two scientists who upended fundamental beliefs about biology by demonstrating that every cell in the body has the potential to grow into every other type of cell have won the Nobel Prize in physiology or medicine.

Sir John Gurdon and Dr. Shinya Yamanaka were honored Monday for "the discovery that mature cells can be reprogrammed" to return to a very early state of development, the Nobel committee said in its citation.

Their research is still years away from yielding a clear breakthrough in medical treatment. But the work has upended the study of intractable conditions including heart disease, diabetes and Alzheimer's by allowing scientists to grow disease-specific and even patient-specific cells for experimentation in the laboratory, experts said.

"It's nothing short of a revolution in how we think of a cell," said Dr. Deepak Srivastava, director of the Roddenberry Center for Stem Cell Biology and Medicine at the Gladstone Institutes in San Francisco, where Yamanaka works one week each month.

Gurdon, 79, performed his seminal work at Oxford University in the late 1950s and early 1960s a good deal of it before Yamanaka was born.

Working with frogs, he showed in 1962 that replacing the nucleus of an egg cell with the nucleus from a cell taken from a tadpole's intestine allowed the egg to develop into a fully functional clone of that tadpole.

The discovery shocked his colleagues in the field. At the time, it wasn't clear whether different types of body cells had different DNA or shared the same genetic instructions and just read them differently, Srivastava said. Gurdon's experiments indicated that cells did contain the same genetic code and that individual cells were capable of creating an entire animal and thus any of its component parts if properly manipulated.

It would take 34 years for Scottish researcher Ian Wilmut to clone Dolly the sheep, replicating the feat in a mammal and capturing the public's imagination.

Yamanaka's achievement was to give scientists an idea of how that cellular reprogramming gets done. When he began this line of work, he was highly criticized in Japan for undertaking such a difficult project.

The Japanese scientist who trained as an orthopedic surgeon before becoming a full-time researcher figured out that activating simple combinations of genes in a mouse skin cell could rewind that cell to an embryo-like state, allowing it to develop anew as any other type of cell in the body.

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British, Japanese scientists share Nobel Prize for stem cell work

UCSF Stem Cell Prof. Wins Nobel Prize

Shinya Yamanaka has won the 2012 Nobel Prize for his discovery of how to transform ordinary adult skin cells into cells that, like embryonic stem cells, are capable of developing into any cell in the human body, the university reported on Monday.

Yamanaka is an MD and a PhD at the Gladstone Institutes, which is affiliated with the University of California, San Francisco.

Yamanaka shares the prize with John B. Gurdon of the Gurdon Institute in Cambridge, England. The prize was awarded for the scientists "discovery that mature cells can be reprogrammed to become pluripotent."

Yamanaka, who works in both San Francisco and Kyoto, is also the director of the Center for iPS Cell Research and Application and a principal investigator at the Institute for Integrated Cell-Material Sciences, both at Kyoto University, UCSF reported.

The former orthopedic surgeon trained in biomedical research at Gladstone in the 1990s, before returning to San Francisco in 2007 as a Gladstone senior investigator and a UCSF anatomy professor.

The best part about this prize is that it will bring attention to and will likely spur the important stem cell work that scientists around the world are conducting, Yamanaka said in a statement. "This iPS technology is for patients and the more scientists who build on it, the faster we can help those who live with chronic or life-threatening diseases.

Initially, the simplicity of Yamanakas technology was met with skepticism, UCSFsaid in a statement.

But he made his data and the DNA of his work publicly available to enable any scientist to work with these new cells. Within months of the 2006 breakthrough, scientists around the world had reproduced and adopted this new approach to generating and studying stem cells.

The impact of Dr. Yamanakas discovery is immense, said Deepak Srivastava, MD, who leads stem cell and cardiovascular research at Gladstone. It suggested that human adult cells retain a greater ability to be modified than previously thought and could potentially be altered into whatever cell type might be desired.

UCSF said in a statement that in addition to avoiding the controversial use of embryonic stem cells, iPS cell technology also represents an entirely new platform for fundamental studies of human disease and the development of therapies to overcome them. Rather than using models made in yeast, flies or mice for disease research, iPS technology allows human stem cells to be created from patients with a specific disease. As a result, the cells contain a complete set of the genes that resulted in that disease representing the potential of a far-superior human model for studying disease and testing new drugs and treatments. In the future, iPS cells could be used in a Petri dish to test both drug safety and efficacy for an individual patient.

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UCSF Stem Cell Prof. Wins Nobel Prize

Mouse stem cells yield viable eggs

Experimental approach might provide insights to support human fertility

Web edition : Thursday, October 4th, 2012

Some baby mice born in Japan are living proof that mouse stem cells taken from embryos or created by reprogramming fetal tissue can be used to make viable egg cells.

Researchers had already created functional sperm from stem cells, and some groups have reported making eggs, or oocytes, but those had never been shown to produce offspring. Now, Mitinori Saitou of Kyoto University in Japan and colleagues have coaxed mouse stem cell to make eggs that produce normal, fertile offspring, the researchers report online October 4 in Science.

This is really pioneering research, says Charles Easley, a reproductive stem cell biologist at Emory University School of Medicine in Atlanta.

The researchers have gone a step beyond making cells that merely look like eggs in a lab dish. This paper produces something that looks like oocytes, smells like oocytes and tastes like oocytes in a way no one has done before, says David Albertini, a reproductive scientist at the University of Kansas Medical Center in Kansas City.

While the evidence that the Japanese researchers have transformed mouse stem cells into functional female gametes is compelling, Albertini doesnt think the feat will be repeated with human stem cells because they are far less flexible than their mouse counterparts. The new technology might provide a way to test the effect that chemicals in the environment may have on fertility and give scientists new information about how eggs age, possibly leading to fertility-extending treatments, he says.

In the new study, Saitou and colleagues started with stem cells from very early mouse embryos as well as stem cells reprogrammed from fetal cells, known as induced pluripotent stem cells. Saitous team manipulated the activity of a few genes in the stem cells to turn them into cells that resemble precursors of gametes, as eggs and sperm are sometimes known.

These primordial germ celllike cells, as they are called, were mixed with support cells from an embryonic ovary and then transplanted into adult mice. Once the precursor cells had developed into oocytes, the researchers pulled them out and fertilized them in the lab before implanting the resulting embryos in female mice.

The oocytes made from either type of stem cell produced mouse pups 3.9 percent of the time. That rate is lower than for primordial germ cells taken directly from mouse embryos, which the researchers found produced pups 17.3 percent of the time. Oocytes taken from the ovaries of 3-week-old mice generated offspring 12.7 percent of the time. Female pups resulting from stem cellderived eggs grew up to become fertile adults, the researchers report.

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Mouse stem cells yield viable eggs

Whitehead Members to Help Establish International Stem Cell Research Center

Newswise CAMBRIDGE, Mass. (October 1, 2012) Three Members of the Whitehead Institute faculty are poised to play significant roles in the establishment of a new stem cell research center based at Skolkovo Institute of Science and Technology (Skolkovo Tech) in suburban Moscow.

Whitehead Founding Member Rudolf Jaenisch, and Members Richard Young and Peter Reddien, will contribute their research, educational, and entrepreneurial expertise to the Skolkovo Center for Stem Cell Research (SCSCR). The center is among the first of three core research facilities to be created at Skolkovo Tech, a private graduate research university in Skolkovo, Russia, established in 2011 in collaboration with Massachusetts Institute of Technology.

Skolkovo Techs research centersknown as Centers for Research, Education, and Innovation (CREIs) are intended to advance scientific understanding in a particular field, develop cutting-edge technologies for potential commercialization, attract world-class scientists to Skolkovo, and train the next generations of promising students. CREIs are international partnerships consisting of researchers from at least three universities or research institutes: Skolkovo Tech, a Russian university or institute, and a non-Russian university. As part of SCSCR, the Whitehead scientists will join a team under the direction of Peter Lansdorp, Director of the European Research Institute for the Biology of Aging at University of Groningen Medical Center UMCG in the Netherlands.

This is a very promising experiment, Lansdorp says. By stimulating international collaboration, it is certain to advance stem cell science while at the same time helping Russian studentstrained by leading stem cell scientists from Whitehead Institute and the Netherlandsto become productive scientists in Moscow."

Within SCSCR, Lansdorp, Jaenisch, Young, Reddien and others will tackle some of the most fundamental challenges to the development of stem-cell-based therapeutics, including optimizing methods for cellular reprogramming, pluripotent stem cell differentiation, and the identification of gene networks involved in stem cell regulation and regeneration.

Although funding details for the stem cell center are not yet final, Skolkovo officials say that a typical CREI receives about $10 million worth of funding, depending on the scope of each research program.

Skolkovos research centers are unique in their synergy between scientific knowledge and practical application, which originates through various institutes working together in a new way, says Skolkovo Tech President Edward Crawley. Russian researchers gain access to cutting edge technologies and the opportunity to integrate into the world's scientific community, our international partners will benefit from the academic knowledge and new ideas produced within Russian institutes, and Skolkovo Tech will attract the world's best scientists to create its educational and research programs.

Written by Matt Fearer

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Whitehead Members to Help Establish International Stem Cell Research Center

Gazette.Net: Names & Faces

Howard

Osiris Therapeutics of Columbia named Hans Klingemann a director, succeeding Gregory H. Barnhill, who died. Klingemann is director of the bone marrow and stem cell transplant program at Tufts Medical Center in Boston and a professor of medicine at Tufts University Medical School.

Chrysalis Holdings of Fulton named Joseph J. Murin chairman, succeeding Paul Thompson III, who remains on the board. Chrysalis also named Murin president of its NewDay USA. Previously, Murin was president of the Government National Mortgage Association, CEO at National Real Estate Information Services, and co-founder and vice chairman of the Collingwood Group.

The Maryland Association of Realtors named David McIlvaine Sr. its 2012 Realtor of the Year. McIlvaine is an associate broker for Keller Williams Select Realtors in Ellicott City.

CCS Mid-Atlantic of Columbia named Roxann Gardner of Ellicott City an account manager. Previously, Gardner was sales director at Fairfield Inn & Suites and president of Network Referral Group. CCS also named Win Anderson a sales representative for Virginia.

Mount St. Mary's University of Emmitsburg named William E. Davies of Harrisburg, Pa., vice president for business and finance. Previously, Davies was CFO and treasurer at the Milton Hershey School and Hershey Trust, and also worked for Hershey Entertainment & Resorts.

Capital Bank of Rockville named Edward Barry CEO, succeeding Stephen Ashman, who remains chairman. Previously, Barry worked for Capital One Bank, Bank of America and Ernst & Young.

Miller, Miller & Canby of Rockville named Helen Whelan a principal in its estates and trusts practice group. Previously, Whelan practiced with Elville & Associates.

Insurance Associates of Rockville named Lexi Stock marketing manager and William Westner claims consultant. Previously, Westner was a claims adjuster at Banner Life.

Ballard Spahr named Debbie A. Klis of counsel and a member of its business and finance department and its investment management, mergers and acquisitions/private equity, securities and tax groups in its Bethesda office.

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University of Maryland study: Neonatal heart stem cells may help mend kids' broken hearts

Public release date: 10-Sep-2012 [ | E-mail | Share ]

Contact: Bill Seiler bseiler@umm.edu 410-328-8919 University of Maryland Medical Center

Baltimore, MD September 10, 2012 Researchers at the University of Maryland School of Medicine, who are exploring novel ways to treat serious heart problems in children, have conducted the first direct comparison of the regenerative abilities of neonatal and adult-derived human cardiac stem cells. Among their findings: cardiac stem cells (CSCs) from newborns have a three-fold ability to restore heart function to nearly normal levels compared with adult CSCs. Further, in animal models of heart attack, hearts treated with neonatal stem cells pumped stronger than those given adult cells. The study is published in the September 11, 2012, issue of Circulation.

"The surprising finding is that the cells from neonates are extremely regenerative and perform better than adult stem cells," says the study's senor author, Sunjay Kaushal, M.D., Ph.D., associate professor of surgery at the University of Maryland School of Medicine and director, pediatric cardiac surgery at the University of Maryland Medical Center. "We are extremely excited and hopeful that this new cell-based therapy can play an important role in the treatment of children with congenital heart disease, many of whom don't have other options."

Dr. Kaushal envisions cellular therapy as either a stand-alone therapy for children with heart failure or an adjunct to medical and surgical treatments. While surgery can provide structural relief for some patients with congenital heart disease and medicine can boost heart function up to two percent, he says cellular therapy may improve heart function even more dramatically. "We're looking at this type of therapy to improve heart function in children by 10, 12, or 15 percent. This will be a quantum leap in heart function improvement."

Heart failure in children, as in adults, has been on the rise in the past decade and the prognosis for patients hospitalized with heart failure remains poor. In contrast to adults, Dr. Kaushal says heart failure in children is typically the result of a constellation of problems: reduced cardiac blood flow; weakening and enlargement of the heart; and various congenital malformations. Recent research has shown that several types of cardiac stem cells can help the heart repair itself, essentially reversing the theory that a broken heart cannot be mended.

Stem cells are unspecialized cells that can become tissue- or organ-specific cells with a particular function. In a process called differentiation, cardiac stem cells may develop into rhythmically contracting muscle cells, smooth muscle cells or endothelial cells. Stem cells in the heart may also secrete growth factors conducive to forming heart muscle and keeping the muscle from dying.

To conduct the study, researchers obtained a small amount of heart tissue during normal cardiac surgery from 43 neonates and 13 adults. The cells were expanded in a growth medium yielding millions of cells. The researchers developed a consistent way to isolate and grow neonatal stem cells from as little as 20 milligrams of heart tissue. Adult and neonate stem cell activity was observed both in the laboratory and in animal models. In addition, the animal models were compared to controls that were not given the stem cells.

Dr. Kaushal says it is not clear why the neonatal stem cells performed so well. One explanation hinges on sheer numbers: there are many more stem cells in a baby's heart than in the adult heart. Another explanation: neonate-derived cells release more growth factors that trigger blood vessel development and/or preservation than adult cells.

"This research provides an important link in our quest to understand how stem cells function and how they can best be applied to cure disease and correct medical deficiencies," says E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs, University of Maryland; the John Z. and Akiko K. Bowers Distinguished Professor; and dean, University of Maryland School of Medicine. "Sometimes simple science is the best science. In this case, a basic, comparative study has revealed in stark terms the powerful regenerative qualities of neonatal cardiac stem cells, heretofore unknown."

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University of Maryland study: Neonatal heart stem cells may help mend kids' broken hearts

Study results: Adult stem cells from bone marrow

Public release date: 3-Jul-2012 [ | E-mail | Share ]

Contact: Sharon Boston sboston@umm.edu 410-328-8919 University of Maryland Medical Center

Baltimore, MD July 3, 2012. Researchers from the University of Maryland School of Maryland report promising results from using adult stem cells from bone marrow in mice to help create tissue cells of other organs, such as the heart, brain and pancreas - a scientific step they hope may lead to potential new ways to replace cells lost in diseases such as diabetes, Parkinson's or Alzheimer's. The research in collaboration with the University of Paris Descartes is published online in the June 29, 2012 edition of Comptes Rendus Biologies, a publication of the French Academy of Sciences.

"Finding stem cells capable of restoring function to different damaged organs would be the Holy Grail of tissue engineering," says lead author David Trisler, PhD, assistant professor of neurology at the University of Maryland School of Medicine.

He adds, "This research takes us another step in that process by identifying the potential of these adult bone marrow cells, or a subset of them known as CD34+ bone marrow cells, to be 'multipotent,' meaning they could transform and function as the normal cells in several different organs."

University of Maryland researchers previously developed a special culturing system to collect a select sample of these adult stem cells in bone marrow, which normally makes red and white blood cells and immune cells. In this project, the team followed a widely recognized study model, used to prove the multipotency of embryonic stem cells, to prove that these bone marrow stem cells could make more than just blood cells. The investigators also found that the CD34+ cells had a limited lifespan and did not produce teratomas, tumors that sometimes form with the use of embryonic stem cells and adult stem cells cultivated from other methods that require some genetic manipulation.

"When taken at an early stage, we found that the CD34+ cells exhibited similar multipotent capabilities as embryonic stem cells, which have been shown to be the most flexible and versatile. Because these CD34+ cells already exist in normal bone marrow, they offer a vast source for potential cell replacement therapy, particularly because they come from a person's own body, eliminating the need to suppress the immune system, which is sometimes required when using adults stem cells derived from other sources," explains Paul Fishman, MD, PhD, professor of neurology at the University of Maryland School of Medicine.

The researchers say that proving the potential of these adult bone marrow stem cells opens new possibilities for scientific exploration, but that more research will be needed to see how this science can be translated to humans.

"The results of this international collaboration show the important role that University of Maryland School of Medicine researchers play in advancing scientific understanding, investigating new avenues for the development of potentially life-changing treatments," says E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine.

This project builds on three decades of collaboration between the American and French researchers, particularly Dr. Bernard Pessac of the University of Paris Descartes and Dr. Trisler at the University of Maryland. Researchers from the Multiple Sclerosis Center of Excellence at the Baltimore Veterans Administration Medical Center also contributed to the study.

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Study results: Adult stem cells from bone marrow

Adult stem cells from bone marrow: Cell replacement/tissue repair potential in adult bone marrow stem cells in animal …

ScienceDaily (July 3, 2012) searchers from the University of Maryland School of Maryland report promising results from using adult stem cells from bone marrow in mice to help create tissue cells of other organs, such as the heart, brain and pancreas -- a scientific step they hope may lead to potential new ways to replace cells lost in diseases such as diabetes, Parkinson's or Alzheimer's.

The research in collaboration with the University of Paris Descartes is published online in the June 29, 2012 edition of Comptes Rendus Biologies, a publication of the French Academy of Sciences.

"Finding stem cells capable of restoring function to different damaged organs would be the Holy Grail of tissue engineering," says lead author David Trisler, PhD, assistant professor of neurology at the University of Maryland School of Medicine.

He adds, "This research takes us another step in that process by identifying the potential of these adult bone marrow cells, or a subset of them known as CD34+ bone marrow cells, to be 'multipotent,' meaning they could transform and function as the normal cells in several different organs."

University of Maryland researchers previously developed a special culturing system to collect a select sample of these adult stem cells in bone marrow, which normally makes red and white blood cells and immune cells. In this project, the team followed a widely recognized study model, used to prove the multipotency of embryonic stem cells, to prove that these bone marrow stem cells could make more than just blood cells. The investigators also found that the CD34+ cells had a limited lifespan and did not produce teratomas, tumors that sometimes form with the use of embryonic stem cells and adult stem cells cultivated from other methods that require some genetic manipulation.

"When taken at an early stage, we found that the CD34+ cells exhibited similar multipotent capabilities as embryonic stem cells, which have been shown to be the most flexible and versatile. Because these CD34+ cells already exist in normal bone marrow, they offer a vast source for potential cell replacement therapy, particularly because they come from a person's own body, eliminating the need to suppress the immune system, which is sometimes required when using adults stem cells derived from other sources," explains Paul Fishman, MD, PhD, professor of neurology at the University of Maryland School of Medicine.

The researchers say that proving the potential of these adult bone marrow stem cells opens new possibilities for scientific exploration, but that more research will be needed to see how this science can be translated to humans.

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