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Ovary stem cells can produce new eggs: study

February 29th, 2012 2:46 am

A new study by researchers from Harvard says that ovaries may be capable of producing new eggs, a discovery which, if true, overturns the long-held belief within the scientific community that a woman is born with a limited number of eggs.

Our current views of ovarian aging are incomplete. Theres much more to the story than simply the trickling away of a fixed pool of eggs, the studys lead researcher, Jonathan Tilly of Harvards Massachusetts General Hospital, told Time magazine.

Special stem cells in ovaries are capable of generating new eggs, according to the study, published in the journal Nature Medicine.

Weve isolated, essentially, the female equivalent of the stem cells that we know exist in men that actively make new sperm. So having these cells now isolated, I think, opens up a lot of opportunities to consider that we simply couldnt fathom before, Dr. Tilly told Voice of America.

Indeed, fertility experts such as Allan Pacey from the University of Sheffield have said the studys findings re-write the rule book. Dr. Pacey told the BBC that the study opens up a number of exciting possibilities for preserving the fertility of women undergoing treatment for cancer, or just maybe for women who are suffering infertility by extracting these cells and making her new eggs in the lab.

In the study, researchers isolated the rare cells from ovaries and placed them in culture outside the body. Over a period of several months, those 100 or so cells were made in to hundreds of thousands of such cells and, as Dr. Tilly told Voice of America, We noticed that these cells would spontaneously generate immature eggs, all on their own, in these cultures.

While the studys findings, if true, are a major change in our understanding of human fertility, independent experts have cautioned that the cells are some way from any potential clinical use.

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Winn: Youmans Neurological Surgery, 6th Edition – Video

February 29th, 2012 2:45 am

01-02-2012 20:50 Effectively perform today's most state-of-the-art neurosurgical procedures with Youmans Neurological Surgery, 6th Edition, edited by H. Richard Winn, MD. Still the cornerstone of unquestioned guidance on surgery of the nervous system, the new edition updates you on the most exciting developments in this ever-changing field. In print and online, it provides all the cutting-edge details you need to know about functional and restorative neurosurgery (FRN)/deep brain stimulation (DBS), stem cell biology, radiological and nuclear imaging, neuro-oncology, and much more. And with nearly 100 intraoperative videos online at http://www.expertconsult.com, as well as thousands of full-color illustrations, this comprehensive, multimedia, 4-volume set remains the clinical neurosurgery reference you need to manage and avoid complications, overcome challenges, and maximize patient outcomes. Learn more at http://www.us.elsevierhealth.com

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Stem Cell Pioneers Converge in Portland to Discuss and Celebrate a Revolutionary New Stem Cell Entering Human Clinical …

February 29th, 2012 2:45 am

SAN DIEGO, CA and PORTLAND, OR--(Marketwire -02/28/12)- Medistem Inc. (Pinksheets: MEDS.PK - News) announced today its Annual "Evening with Medistem" Event will take place in Portland, Oregon on March 7th, 2012. The event is being hosted by Vladimir Zaharchook, Vice Chairman at Medistem, Inc., and will feature stem cell luminaries and pioneers working with Medistem including Dr. Amit Patel, Director of Regenerative Medicine at University of Utah and the first person to administer stem cells into patients with heart failure, Dr. Michael Murphy, Vascular Surgeon at Indiana University and Principal Investigator for Medistem's FDA clinical trial in patients with risk of amputation, and Dr. Alan Lewis, former CEO of the Juvenile Diabetes Research Foundation, advisory board member of Medistem.

In 2007 Medistem discovered an entirely new type of stem cell, the Endometrial Regenerative Cell (ERC). This cell has proven it is a "universal donor" and can be used to treat many more conditions compared to other types of stem cells. The company received FDA clearance to begin clinical trials in September of 2011 for critical limb ischemia, a condition that is associated with amputation. Medistem is also running a Phase II clinical trial for heart failure using the new stem cell. The ERC stem cell does not involve the highly controversial use of fetal tissue, can be produced very economically and administered to the patient in a very simple manner. Medistem is exploring ways to expand clinical trials of its stem cell into other diseases.

"Stem cells and regenerative medicine offer hope in clinical conditions in which hope previously did not exist," said Dr. Stanley Cohan, Head of Neurology at the St Vincent's Hospital, the largest center for treatment of multiple sclerosis in the Pacific Northwest, who will be attending the event. "We are honored in the Portland community to have this distinguished team of accomplished researchers and medical doctors convene here and discuss with us possible collaborations."

"As a long-time member of the Portland academic community, it is exciting to have companies such as Medistem to visit us and share their experiences 'from the trenches' of what it takes to push a cellular drug through the FDA," said Dr. Shoukrat Milipotiv, Associate Scientist in the Division of Reproductive & Developmental Sciences of ONPRC, Oregon Stem Cell Center and Departments of Obstetrics & Gynecology and Molecular & Medical Genetics, and co-director of the ART/ESC core at the Center. He is an internationally recognized researcher in the area of stem cells.

"The Event is an annual celebration to honor our team and collaborators for the successes of the previous year, while at the same time educate the local business and medical community on the latest research on stem cells not just at Medistem but internationally," said Thomas Ichim, Ph.D Chief Executive Officer of Medistem Inc. "2012 is particularly exciting for us due to approvals for two clinical trials, and the initiation of patient treatments within this context."

About Medistem Inc.

Medistem Inc. is a biotechnology company developing technologies related to adult stem cell extraction, manipulation, and use for treating inflammatory and degenerative diseases. The company's lead product, the endometrial regenerative cell (ERC), is a "universal donor" stem cell being developed for critical limb ischemia and heart failure.

Cautionary Statement

This press release does not constitute an offer to sell or a solicitation of an offer to buy any of our securities. This press release may contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Future events and actual results could differ materially from those set forth in, contemplated by, or underlying the forward-looking information. Factors which may cause actual results to differ from our forward-looking statements are discussed in our Form 10-K for the year ended December 31, 2007 as filed with the Securities and Exchange Commission.

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The 27th Colloque Médecine et Recherche of the Fondation Ipsen in the Alzheimer Disease series: “Proteopathic Seeds …

February 29th, 2012 2:44 am

PARIS--(BUSINESS WIRE)--

In the mid 1980s, Stanley Prusiner startled the scientific world by claiming that transmissible neurodegenerative diseases such as Creutzfeldt-Jakob in humans and Bovine Spongiform Encephalopathy (BSE; mad cow disease) were caused by self-replicating protein molecules, which he named prions. Painstaking work to establish that prion proteins could replicate without the need for genetic material won him the Nobel prize in 1997. What at first seemed an unusual mechanism restricted to a rather rare group of diseases has now become central to the study of all neurodegenerative conditions: the pathogenic proteins that characterise these diseases all seem to behave like prions. The implications for understanding how these diseases are transmitted through the nervous system and the possibility that environmental contamination may account for the sporadic forms of these diseases, as well as therapeutic possibilities, were among the topics discussed by the thirteen international experts, including two Nobel Prize winners, at the 27th annual colloquium on Alzheimers disease, hosted by the Fondation IPSEN. The meeting, hold in Paris on February 27, 2012, has been organized by Mathias Jucker (University of Tbingen, Germany) and Yves Christen (Fondation IPSEN, Paris).

Prions are Janus-like proteins synthesised by neurons: in their normal, globular conformation they participate in cellular functions but in certain circumstances they adopt a pleated -sheet configuration, which forms insoluble fibrous aggregates that disrupt cell function. This aggregated form is found in neurons in a group of neurodegenerative diseases known as the transmissible spongiform encephalopathies, which include Kuru, Creutzfeldt-Jakob disease (CJD) in humans, BSE in cattle and scrapie in sheep. All of these diseases can be transmitted by contact with brain material from affected individuals the cause of great concern in the late 1980s and early 1990s when people developed a form of CJD after eating products from cows with BSE.

By the 1980s, a long hunt had failed to find either a bacterial or viral agent causing these diseases. Stanley Prusiner and his colleagues proposed instead that the infectious agent was the -sheet form of the prion protein, which was able to replicate using itself as a template. As the first claim for replication without the need for nucleic acids, this was to say the least controversial. Now it is well accepted that rogue molecules in the -sheet conformation, now known as prions, can act as a seed, converting normal prion proteins into -sheet type molecules. These adopt a fibrillar configuration and aggregate into an amyloid-like deposit that disrupts the neurons function. Prions released from cells are taken up by neighbours and trigger the same cascade of transformation and aggregation. Genetics still plays a part, because various mutations in the prion protein gene promote this transformation, while some polymorphisms (substitution of one base in the gene sequence for another) make individuals more susceptible to developing a prion disease.

The parallels with Alzheimers disease (AD) were soon noted: a cellular protein, in this case the amyloid- peptide, adopts a -sheet, fibrillar conformation that aggregates in the brain as amyloid plaques; again genetics plays a part, at least in early-onset, familial AD, which is associated with mutations in amyloid-s parent protein, the amyloid precursor protein. More recently, it has become clear that this prion-like pattern is common to all the neurodegenerative diseases, including Parkinsons, Huntingtons and motor neuron disease (Stanley Prusiner, University of California San Francisco, San Francisco, USA): each is characterised by a disease-specific cellular protein that transforms into a -sheet configuration that subsequently aggregates. Moreover, mutations associated with familial forms of the diseases have now been identified for all these signature proteins. As a consequence these conditions are now being designated as protein misfolding disorders (Claudio Soto, University of Texas Houston Medical School, Houston, USA) and the proteins responsible could be considered as mammalian prions (Prusiner).

If the misfolded proteins associated with the various neurodegenerative diseases do behave like prions, they should be capable of triggering the transformation of the cellular protein in unaffected cells. Transfer of a systemic (non-neural) amyloidosis between mice was first demonstrated over 40 years ago (Per Westermark, Uppsala University, Uppsala, Sweden). Several speakers at the meeting have presented data supporting this hypothesis for various neurodegenerative diseases, either by injecting a brain homogenate from mice genetically engineered to develop the disease into the brains of susceptible but disease-free animals (Prusiner; Mathias Jucker, Hertie-Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Tbingen, Germany; Soto; Michel Goedert, MRC Laboratory of Molecular Biology, Cambridge, UK; Patrik Brundin, Lund University, Lund, Sweden; Virginia Lee, University of Pennsylvania School of Medicine, Philadelphia, USA); by injecting synthetic protein fibrils into brains (Lee); or by testing purified protein extracts on neuron cultures (Anne Bertolotti, MRC Laboratory of Molecular Biology, Cambridge, UK; Ron Kopito, Stanford University, Stanford, USA). Another clear indication of transcellular induction comes from Parkinsons disease patients who have had stem-cell transplants: -sheet proteins have been found in the neurons derived from the stem cells (Brundin).

This triggering ability of the aberrant proteins, which has gained them the label of proteopathic seeds, also seems to be responsible for the temporal spread of degeneration through the brain that is typical of the neurodegenerative diseases (Jucker; Brundin; Lee). Perhaps more significant, the aberrant proteins have been found in the brain after intra-peritoneal injection or blood transfusion (Soto); as with prions, transport along the vagal nerve seems to be the most likely route into the brain (Prusiner; Brundin). This opens up the possibility of an environmental causation for the many patients with a neurodegenerative disease who do not have hereditary links (Jucker; Soto; Westermark).

The mechanisms underlying proteopathic seeding are still unclear. The spread of the -sheet transformation seems to depend on both the configuration of the seed itself and the genetic constitution of the animal again very like the prion diseases (Jucker; Goedert). The uptake of the seed proteins into neurons is being examined in culture (Bertolotti; Kopito) and model systems (Brundin). The key seems to be in the interaction between the seed protein and cell membranes and, in some cases at least, helper proteins are required (Brundin).

To understand how seeding works, it is essential to know the structure of the -sheet proteins. Taking amyloid- as an example, the conditions that determine what type of fibril and aggregates will form, and how this relates to the mutations in the amyloid precursor protein will be discussed (Robert Tycko, National Institutes of Health, NIDDK, Bethesda, USA). Cooperativity between -sheet molecules may also be important in aggregation (Roland Riek, ETH Zrich, Zrich, Switzerland). Helpful insights can also come from systemic diseases in which amyloid accumulates, such as AA amyloidosis. Amyloid, a generic term for protein aggregates, is in this case produced by the inflammatory protein serum amyloid A (Westermark). There is evidence that AA amyloid formation can be triggered by other types of amyloid molecule, leading to speculation that amyloid fibrils found in the environment and food could cross-seed amyloid formation in the body or brain.

As knowledge about proteopathic seeding accumulates, new prospects for therapeutic intervention open up (Peter Lansbury, Brigham and Womens Hospital, Boston, USA). The initial conversion of functional globular protein into potentially pathogenic -sheet form, the seeding cascade that coverts further globular protein to -sheet, and the mechanisms by which neurons take up prion-like -sheet molecules are all potential targets. The discovery that amyloid- seeds are partly soluble and may be present in body fluids offers a possible alternative strategy for an early diagnostic (Jucker).

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Bioheart Announces University of Miami as Clinical Site for ANGEL Trial of LipiCell(TM)

February 29th, 2012 2:42 am

SUNRISE, Fla., Feb. 28, 2012 (GLOBE NEWSWIRE) -- Bioheart, Inc. (BHRT.OB) announced that the company will conduct the ANGEL trial using adipose (fat) derived stem cell technology or LipiCell(TM) at the University of Miami Miller School of Medicine. Bioheart recently applied to the FDA to begin trials using adipose derived stem cells in patients with chronic ischemic cardiomyopathy.

"Dr. Joshua Hare and the University of Miami are world leaders in the field of stem cell research," said Mike Tomas, President and CEO of Bioheart. "We look forward to working with these acclaimed experts and bringing the LipiCell(TM) technology to patients in the U.S."

The clinical protocol of the ANGEL trial is designed to assess the safety and cardiovascular effects of intramyocardial implantation of autologous adipose derived stem cells (LipiCell(TM)) in patients with chronic ischemic cardiomyopathy. Joshua Hare, MD, Director of the Interdisciplinary Stem Cell Institute at the University of Miami Miller School of Medicine is the principle investigator of the clinical program.

The Interdisciplinary Stem Cell Institute was established to capitalize on pioneering work in the use of adult stem cells for the repair of malfunctioning human organs. The goal of the Institute is to find new treatments for heart disease, neurological disease, bone disease, diabetes, cancer, eye diseases and other chronic, debilitating, or incurable diseases. University of Miami scientists have led in the development of procedures to extract adult stem cells and have conducted ground breaking research in cell-based therapy for the diseased human heart.

About Bioheart, Inc.

Bioheart is committed to maintaining our leading position within the cardiovascular sector of the cell technology industry delivering cell therapies and biologics that help address congestive heart failure, lower limb ischemia, chronic heart ischemia, acute myocardial infarctions and other issues. Our goals are to cause damaged tissue to be regenerated, if possible, and to improve a patient's quality of life and reduce health care costs and hospitalizations.

Specific to biotechnology, we are focused on the discovery, development and, subject to regulatory approval, commercialization of autologous cell therapies for the treatment of chronic and acute heart damage and peripheral vascular disease. Our leading product, MyoCell, is a clinical muscle-derived cell therapy designed to populate regions of scar tissue within a patient's heart with new living cells for the purpose of improving cardiac function in chronic heart failure patients. For more information on Bioheart, visit http://www.bioheartinc.com.

Forward-Looking Statements: Except for historical matters contained herein, statements made in this press release are forward-looking statements. Without limiting the generality of the foregoing, words such as "may," "will," "to," "plan," "expect," "believe," "anticipate," "intend," "could," "would," "estimate," or "continue" or the negative other variations thereof or comparable terminology are intended to identify forward-looking statements.

Forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Also, forward-looking statements represent our management's beliefs and assumptions only as of the date hereof. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future.

The Company is subject to the risks and uncertainties described in its filings with the Securities and Exchange Commission, including the section entitled "Risk Factors" in its Annual Report on Form 10-K for the year ended December 31, 2010, and its Quarterly Report on Form 10-Q for the quarter ended September 30, 2011.

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Japanese Scientists Use A Chemical In Bad Breath To Produce Stem Cells

February 29th, 2012 2:42 am

Scientists are usinghydrogen sulphide, the chemical found in stink bombs and bad breath, to strengthen the purity of stem cells, according to the Journal of Breath Research.

Though toxic in large quantities, hydrogen sulphide was shown to increase the purity level of stem cells, which keeps them from reverting to other tissues when they are implanted in a new organ.

In this study, stem cells were taken from dental pulp and converted to liver cells. Hopefully, these cells would help regenerate the liver in case the organ was damaged.

Unfortunately, there isn't a ton of dental pulp (the part in the middle of the tooth) to be harvested for this purpose. The study did not say how many stem cells were produced from the dental pulp.

It is nice to know that hydrogen sulphide which is also found in farts can be used productively, if harvested correctly.

(via WedMD)

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Japanese Scientists Use A Chemical In Bad Breath To Produce Stem Cells

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IU doctors land large grant for adult stem cell research

February 29th, 2012 2:42 am

INDIANAPOLIS -

An announcement involving cutting edge research of adult stem cells has doctors at Indiana University excited.

The doctors have been included in a $63 million National Institutes of Health project nabbing spots the Cleveland Clinic and Vanderbilt lost and patients here will benefit from.

Dr. Mike Murphy and Dr. Keith March will head up the IU effort, one of seven nationwide sites just named to recruit 500 patients over the next seven years who have heart attacks, heart failure or poor circulation in the legs for adult stem cell research.

"What we are doing is taking the cells from one part of the body and bringing them to another area that needs repair more urgently,' said March. "They are able to repair a variety of tissues by either decreasing inflammation by helping tissues not to die if they are at risk of death, or by helping them even to grow and regenerate."

The new NIH Cardiovascular Cell Therapy Research Network distinction follows years of work with patients like Ruth Diggs, who was diagnosed with peripheral arterial disease in New York.

"They were just telling me the only solution for me was to amputate the leg," Diggs said.

Unhappy with that option, Ruth traveled to Indiana and enrolled in a clinical trial at IU, where adult stem cells were injected in to her leg. That led to regeneration and Ruth's leg was saved.

"The fact that she has her leg, we are very, very grateful," said Ruth's daughter, Melvina Jagack.

Murphy showed images of blood flow through the leg of a male patient from Maine who enrolled in the clinical trial.

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‘Scope for innovation in genetic medicine’

February 28th, 2012 4:50 pm

There is a tremendous opportunity in genetic medicine for innovation and for new players to make significant contributions, because it is still experimental, noted biologist and Nobel Laureate Dr David Baltimore said yesterday.
“Today, it is mainly the province of biotechnology companies and universities, not big pharmaceutical companies,” he observed in a keynote presentation at the Qatar International Conference on Stem Cell Science and Policy 2012.
There are new genetic tools available – though they are still experimental - to treat diseases which involve adding, subtracting or modifying genes in the cells of the body.
“However, they are powerful tools and I am confident they will be an important part of the medicine of the future,” he said.
Speaking on ‘The hematopoietic stem cell (HSC) as a target for therapy against cancer and Aids,’ Dr Baltimore explained that HSCs are one of the few cell types routinely used for bone marrow transplant.
The HSCs are easily accessible, retroviruses can be used to carry genes into these stem cells, the genes are then expressed in all of cells that derive from the HSC and can correct inherited defects and bring genes that perform therapy under a programme called engineering immunity.
“Though the human immune system is a wondrous creation of evolution yet it is not without certain limitations. One, in particular, is its poor ability to stop the growth of cancer cells– another is its hosting of HIV.
“In the case of cancer, the machinery of immunity can attack cancers but it rarely attacks with the necessary power. For HIV, the ability of the virus to use the CD4 and CCR5 proteins as receptors means that CD4 cells are the major cell type in which the virus grows.
“We have been trying to supply genes to the immune system by gene transfer methods that would improve its ability to block cancer and block infection of CD4 cells by HIV.
“For cancer, we have focused on T cell receptor genes. For HIV, we have used a small interfering ribonucleic acid (siRNA) targeted to CCR5. We have been quite successful in mice with both strategies and are now moving to humans.
“In both cases, our experiments with mice have focused on putting genes into HSCs as, once these cells are altered, they provide modified blood cells to the body for life.
“In our human cancer trials we first used peripheral T cells for modification with dramatic effect but it has been transient.
“We are now moving to stem cells. For the siRNA against CCR5, we plan to initiate trials within six months using autologous, gene-modified stem cells,” he added.
The ensuing panel discussion on ‘Opportunities and challenges for stem cell research,’ saw Prof Irving Weissman (Stanford Institute for Stem Cell Biology and Regenerative Medicine) cautioning against ‘phoney organisations engaged in stem cell therapy.’
Prof Juan Carlos Izpisua Belmonte (Salk Institute for Biological Studies, US) stated that stem cells derived from umbilical cord blood should be considered as one of the key cells for use in regenerative medicine.
The session also featured Dr Alan Trounson (California Institute of Regenerative Medicine), Prof Roger Pedersen (The Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge), Dr Lawrence Corey (University of Washington) and with Dr Richard Klausner (managing partner of biotechnology venture capital firm The Column Group) as moderator.
Earlier, Ambassador Edward P Djerejian (founding director, James A Baker III Institute for Public Policy, Rice University, Houston, Texas, US) spoke about the collaboration with Qatar Foundation on stem cell research.

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‘Scope for innovation in genetic medicine’

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Bioheart Announces University of Miami as Clinical Site for ANGEL Trial of LipiCell(TM)

February 28th, 2012 4:50 pm

SUNRISE, Fla., Feb. 28, 2012 (GLOBE NEWSWIRE) -- Bioheart, Inc. (BHRT.OB) announced that the company will conduct the ANGEL trial using adipose (fat) derived stem cell technology or LipiCell(TM) at the University of Miami Miller School of Medicine. Bioheart recently applied to the FDA to begin trials using adipose derived stem cells in patients with chronic ischemic cardiomyopathy.

"Dr. Joshua Hare and the University of Miami are world leaders in the field of stem cell research," said Mike Tomas, President and CEO of Bioheart. "We look forward to working with these acclaimed experts and bringing the LipiCell(TM) technology to patients in the U.S."

The clinical protocol of the ANGEL trial is designed to assess the safety and cardiovascular effects of intramyocardial implantation of autologous adipose derived stem cells (LipiCell(TM)) in patients with chronic ischemic cardiomyopathy. Joshua Hare, MD, Director of the Interdisciplinary Stem Cell Institute at the University of Miami Miller School of Medicine is the principle investigator of the clinical program.

The Interdisciplinary Stem Cell Institute was established to capitalize on pioneering work in the use of adult stem cells for the repair of malfunctioning human organs. The goal of the Institute is to find new treatments for heart disease, neurological disease, bone disease, diabetes, cancer, eye diseases and other chronic, debilitating, or incurable diseases. University of Miami scientists have led in the development of procedures to extract adult stem cells and have conducted ground breaking research in cell-based therapy for the diseased human heart.

About Bioheart, Inc.

Bioheart is committed to maintaining our leading position within the cardiovascular sector of the cell technology industry delivering cell therapies and biologics that help address congestive heart failure, lower limb ischemia, chronic heart ischemia, acute myocardial infarctions and other issues. Our goals are to cause damaged tissue to be regenerated, if possible, and to improve a patient's quality of life and reduce health care costs and hospitalizations.

Specific to biotechnology, we are focused on the discovery, development and, subject to regulatory approval, commercialization of autologous cell therapies for the treatment of chronic and acute heart damage and peripheral vascular disease. Our leading product, MyoCell, is a clinical muscle-derived cell therapy designed to populate regions of scar tissue within a patient's heart with new living cells for the purpose of improving cardiac function in chronic heart failure patients. For more information on Bioheart, visit http://www.bioheartinc.com.

Forward-Looking Statements: Except for historical matters contained herein, statements made in this press release are forward-looking statements. Without limiting the generality of the foregoing, words such as "may," "will," "to," "plan," "expect," "believe," "anticipate," "intend," "could," "would," "estimate," or "continue" or the negative other variations thereof or comparable terminology are intended to identify forward-looking statements.

Forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Also, forward-looking statements represent our management's beliefs and assumptions only as of the date hereof. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future.

The Company is subject to the risks and uncertainties described in its filings with the Securities and Exchange Commission, including the section entitled "Risk Factors" in its Annual Report on Form 10-K for the year ended December 31, 2010, and its Quarterly Report on Form 10-Q for the quarter ended September 30, 2011.

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Future Fertility Fix? Egg-Producing Stem Cells Found in Human Ovaries

February 28th, 2012 5:28 am

Study Suggests Women May Be Able to Make More Eggs as They Age

By Brenda Goodman, MA
WebMD Health News

Reviewed by Laura J. Martin, MD

Feb. 26, 2012 -- Scientists say they have found a way to use ovarian stem cells to perhaps one day help infertile women get pregnant -- or add years to a woman's reproductive cycle.

In a study published in Nature Medicine, researchers report finding egg-producing stem cells in human ovaries. They also report being able to make some of those ovarian stem cells grow into immature eggs that may someday be useful for reproduction.

At this point, such "seed" eggs can't be fertilized by sperm. But if scientists are able to entice them to mature and can prove they can be fertilized and grow into embryos -- a feat that has been reported in mice -- it would overturn a long-held scientific belief that women can't make new eggs as they get older.

"What it does is really open a door into human reproduction that 10 years ago didn't even exist," says researcher Jonathan L. Tilly, PhD, director of the Vincent Center for Reproductive Biology at Massachusetts General Hospital, in Boston.

Outside experts agree. They say the findings could have profound importance for reproductive medicine and aging, allowing doctors not only to restore a woman's fertility but also to potentially delay menopause.

"I think the significance of this work is like reporting that we found microorganisms on Mars," says Kutluk Oktay, MD, who directs the Division of Reproductive Medicine and the Institute for Fertility Preservation at New York Medical College in Valhalla, N.Y.

Still, It's a Long Way to Mars

"It's a proof of principle that they could do it," says David F. Albertini, PhD, director of the Center for Reproductive Sciences at the University of Kansas Medical Center in Kansas City, Kan.

"The world wants to know today if we're ready to restore fertility in women, whether they've aged or been treated for cancer or whatever," Albertini says, adding that he doesn't think that's on the horizon. "This is an extremely rare event, at best."

The egg-generating stem cells the researchers were able to extract from ovaries were very rare. The researchers only came across one for every 10,000 or so ovarian cells that they counted.

But when they took those cells and implanted them back into human ovarian tissue, they divided and essentially made young eggs.

Tilly says his team stopped short of trying to make one of the eggs functional because "for a lot of reasons, as it should be," it is illegal in the U.S. to experimentally fertilize human eggs.

"We think the evidence provided clearly indicates that this very unique, newly discovered pool of cells does exist in women," he says.

A Lot of Potential

"It's a really exciting result," says Evelyn Telfer, PhD, a cell biology expert at the University of Edinburgh in Scotland.

"What we've previously believed is that you don't get new eggs formed during your adult life. This discovery shows that there's the potential for them to be formed, no question about that," Telfer says, "but it doesn't actually show that they're being formed under normal conditions."

Indeed, she notes, experience would suggest otherwise. Women, after all, do lose their fertility as they age.

"There are cells there that under certain conditions have the potential to form [eggs]. That's the really exciting part of this work. And of course they can be used. There's a practical application," she says.

Telfer has pioneered a technique that allows her to take immature human eggs and turn them into mature, fertilizable eggs outside the body. She has already partnered with Tilly to try to take his "seed" eggs to the next stage of development. With special government permission, she says, they may even be able to try to experimentally fertilize the eggs.

"It's actually opening up a whole new field of research, to define these cells, to characterize these cells, and to use them in a practical way," she says.

Tilly says that by using egg-generating stem cells to make large numbers of viable eggs, doctors might one day be able to cut the expense of in vitro fertilization (IVF), since women would no longer have to go through multiple cycles of treatment to harvest enough eggs to generate a pregnancy.

'True Emancipation of Women'

"If Dr. Tilly can reverse the biologic clock or halt it, and start making eggs from stem cells, it's fantastic," says Avner Hershlag, MD, chief of the Center for Human Reproduction at North Shore University Hospital in Manhasset, N.Y.

"This is the true reproductive emancipation of women," he tells WebMD. "You will be free to a) not compromise on who you share your life and share your kids with, and b) like any man, you will have the freedom to develop a full professional life and not have to stop everything because you are having children."

But Hershlag notes that such an advance might still be years away.

For women who are worried they'll run out of time to have children, Hershlag says there is technology available that helps women buy more time to have a baby. "Her best bet is actually, right now, to freeze her eggs if she wants to delay reproduction."

SOURCES: White, Y. Nature Medicine, Feb. 26, 2012.News release, Massachusetts General Hospital.Jonathan L. Tilly, PhD, director of the Vincent Center for Reproductive Biology at Massachusetts General Hospital; professor, department of obstetrics, gynecology, and reproductive biology, Harvard Medical School, Boston.Kutluk Oktay, MD, director, Division of Reproductive Medicine and the Institute for Fertility Preservation, New York Medical College, Valhalla, N.Y.David F. Albertini, PhD, director, Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, Kan.Evelyn Telfer, PhD, reader in cell biology, University of Edinburgh, Scotland.Avner Hershlag, MD, chief, the Center For Human Reproduction, North Shore University Hospital, Manhasset, N.Y.

©2012 WebMD, LLC. All Rights Reserved.

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Egg-producing stem cells isolated from adult human ovaries

February 28th, 2012 5:28 am

ScienceDaily (Feb. 26, 2012) — For the first time, Massachusetts General Hospital (MGH) researchers have isolated egg-producing stem cells from the ovaries of reproductive age women and shown these cells can produce what appear to be normal egg cells or oocytes. In the March issue of Nature Medicine, the team from the Vincent Center for Reproductive Biology at MGH reports the latest follow-up study to their now-landmark 2004 Nature paper that first suggested female mammals continue producing egg cells into adulthood.

"The primary objective of the current study was to prove that oocyte-producing stem cells do in fact exist in the ovaries of women during reproductive life, which we feel this study demonstrates very clearly," says Jonathan Tilly, PhD, director of the Vincent Center for Reproductive Biology in the MGH Vincent Department of Obstetrics and Gynecology, who led the study. "The discovery of oocyte precursor cells in adult human ovaries, coupled with the fact that these cells share the same characteristic features of their mouse counterparts that produce fully functional eggs, opens the door for development of unprecedented technologies to overcome infertility in women and perhaps even delay the timing of ovarian failure."

The 2004 report from Tilly's team challenged the fundamental belief, held since the 1950s, that female mammals are born with a finite supply of eggs that is depleted throughout life and exhausted at menopause. That paper and a 2005 follow-up published in Cell showing that bone marrow or blood cell transplants could restore oocyte production in adult female mice after fertility-destroying chemotherapy were controversial; but in the intervening years, several studies from the MGH-Vincent group and other researchers around the world have supported Tilly's work and conclusions.

These supporting studies include a 2007 Journal of Clinical Oncology report from the MGH-Vincent team that showed female mice receiving bone marrow transplants after oocyte-destroying chemotherapy were able to have successful pregnancies, delivering pups that were their genetic offspring and not of the marrow donors. A 2009 study from a team at Shanghai Jiao Tong University in China, published in Nature Cell Biology, not only isolated and cultured oocyte-producing stem cells (OSCs) from adult mice but also showed that those OSCs, after transplantation into the ovaries of chemotherapy-treated female mice, gave rise to mature oocytes that were ovulated, fertilized and developed into healthy offspring.

"That study singlehandedly deflated many of the arguments from critics of our earlier Nature paper by showing that oocyte-producing stem cells exist in mice and could develop into fully functional eggs," says Tilly. Another paper from a west-coast biotechnology company, published in Differentiation in 2010, provided further independent confirmation of Tilly's earlier conclusions regarding the presence of oocyte-producing stem cells in ovaries of adult mice.

Tilly is quick to point out, however, "These follow-up studies, while providing definitive evidence that oocyte-producing stem cells exist in ovaries of adult female mammals, were not without their limitations, leaving the question open in some scientific circles of whether the adult oocyte pool can be renewed. For example, the protocol used to isolate OSCs in the 2009 Nature Cell Biology study is a relatively crude approach that often results in the contamination of desired cells by other cell types." To address this, the MGH-Vincent team developed and validated a much more precise cell-sorting technique to isolate OSCs without contamination from other cells.

The 2009 study from China also had isolated OSCs based on cell-surface expression of a marker protein called Ddx4 or Mvh, which previously had been found only in the cytoplasm of oocytes. This apparent contradiction with earlier studies raised concerns over the validity of the protocol. Using their state-of-the-art fluorescence-activated cell sorting techniques, the MGH-Vincent team verified that, while the marker protein Ddx4 was indeed located inside oocytes, it was expressed on the surface of a rare and distinct population of ovarian cells identified by numerous genetic markers and functional tests as OSCs.

To examine the functional capabilities of the cells isolated with their new protocol, the investigators injected green fluorescent protein (GFP)-labeled mouse OSCs into the ovaries of normal adult mice. Several months later, examination of the recipient mouse ovaries revealed follicles containing oocytes with and without the marker protein. GFP-labeled and unlabeled oocytes also were found in cell clusters flushed from the animals' oviducts after induced ovulation. The GFP-labeled mouse eggs retrieved from the oviducts were successfully fertilized in vitro and produced embryos that progressed to the hatching blastocyst stage, a sign of normal developmental potential. Additionally, although the Chinese team had transplanted OSCs into ovaries of mice previously treated with chemotherapy, the MGH-Vincent team showed that it was not necessary to damage the recipient mouse ovaries with toxic drugs before introducing OSCs.

In their last two experiments, which Tilly considers to be the most groundbreaking, the MGH-Vincent team used their new cell-sorting techniques to isolate potential OSCs from adult human ovaries. The cells obtained shared all of the genetic and growth properties of the equivalent cells isolated from adult mouse ovaries, and like mouse OSCs, were able to spontaneously form cells with characteristic features of oocytes. Not only did these oocytes formed in culture dishes have the physical appearance and gene expression patterns of oocytes seen in human ovaries -- as was the case in parallel mouse experiments -- but some of these in-vitro-formed cells had only half of the genetic material normally found in all other cells of the body. That observation indicates that these oocytes had progressed through meiosis, a cell-division process unique to the formation of mature eggs and sperm.

The researchers next injected GFP-labeled human OSCs into biopsied human ovarian tissue that was then grafted beneath the skin of immune-system-deficient mice. Examination of the human tissue grafts 7 to 14 days later revealed immature human follicles with GFP-negative oocytes, probably present in the human tissue before OSC injection and grafting, as well as numerous immature human follicles with GFP-positive oocytes that would have originated from the injected human OSCs.

"These experiments provide pivotal proof-of-concept that human OSCs reintroduced into adult human ovarian tissue performed their expected function of generating new oocytes that become enclosed by host cells to form new follicles," says Tilly, a professor of Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School and chief of Research at the MGH Vincent Department of Obstetrics and Gynecology. "These outcomes are exactly what we see if we perform the same experiments using GFP-expressing mouse OSCs, and GFP-expressing mouse oocytes formed that way go on to develop into fully functional eggs.

"In this paper we provide the three key pieces of evidence requested by those who have been skeptical of our previous work," he adds. "We developed and extensively validated a cell-sorting protocol to reliably purify OSCs from adult mammalian ovaries, proving once again that these very special cells exist. We tested the function of mouse oocytes produced by these OSCs and showed that they can be fertilized to produce healthy embryos. And we identified and characterized an equivalent population of oocyte-producing stem cells isolated from adult human ovaries."

Among the many potential clinical applications for these findings that Tilly's team is currently exploring are the establishment of human OSC banks -- since these cells, unlike human oocytes, can be frozen and thawed without damage -- the identification of hormones and factors that accelerate the formation of oocytes from human OSCs, the development of mature human oocytes from OSCs for in vitro fertilization, and other approaches to improve the outcomes of IVF and other infertility treatments.

Tilly notes that an essential part of his group's accomplishment was collaboration with study co-author Yasushi Takai, MD, PhD, a former MGH research fellow on Tilly's team and now a faculty member at Saitama Medical University in Japan. Working with his clinical colleagues at Saitama, Takai was able to provide healthy ovarian tissue from consenting patients undergoing sex reassignment surgery, many in their 20s and early 30s. Co-lead authors of the Nature Medicine report are Yvonne White, PhD, and Dori Woods, PhD, of the Vincent Center for Reproductive Biology at MGH. Additional co-authors are Osamu Ishihara, MD, PhD, and Hiroyuki Seki, MD, PhD, of Saitama Medical University.

The study was supported by a 10-year MERIT Award to Tilly from the National Institute on Aging, a Ruth L. Kirschstein National Research Service Award from the National Institutes of Health, the Henry and Vivian Rosenberg Philanthropic Fund, the Sea Breeze Foundation, and Vincent Memorial Hospital Research Funds.

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Journal Reference:

Yvonne A R White, Dori C Woods, Yasushi Takai, Osamu Ishihara, Hiroyuki Seki, Jonathan L Tilly. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nature Medicine, 2012; DOI: 10.1038/nm.2669

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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Respite home lets families with ailing children get away

February 28th, 2012 5:28 am

The Pincus family, of Manassas, Va. at the respite house in Pinnacle Falls. From left: Lori, Lauren, Brooke, Lacey, Lexus, Blake, Don. The family spent a week at the Believe in Tomorrow Foundation respite house in Pinnacle Falls, Zirconia last year. The foundation provides respite homes for military families with critically-ill children and is celebrating the one-year anniversary of the Pinnacle Falls property. Blake suffered from lymphoma cancer and now is waiting for a kidney transplant.

Buy Photo Photo provided Published: Monday, February 27, 2012 at 11:40 p.m. Last Modified: Monday, February 27, 2012 at 11:40 p.m.

ZIRCONIA - It's been a year since the Pincus family found much-needed relaxation in the Blue Ridge Mountains at a respite house nestled in the Pinnacle Falls development.

Don and Lori Pincus' son, 17-year-old Blake, was diagnosed with a type of lymphoma cancer in 2009, and that eventually led them to the Believe in Tomorrow Foundation.

In 2011, the Pincuses became the first family to vacation at the foundation's respite house at Pinnacle Falls in Zirconia. Now the foundation is celebrating the one-year anniversary of the home that serves military families with children battling life-threatening illnesses.

Blake received a kidney transplant from his mom when he was just 2 years old. In May 2009, he was diagnosed with Post-Transplant Lymphoproliferative Disorder.

Between 2009 and 2010, Blake and his family stayed at the Believe In Tomorrow Children's House at Johns Hopkins and at St. Casimir while he underwent multiple rounds of chemotherapy and radiation treatments, followed by a bone marrow and stem-cell transplant to prevent the disease from returning.

Although the transplant was successful, renal failure caused by the treatments has forced Blake to remain on dialysis until he can get another kidney transplant.

Blake is doing well as he waits, said his father, Don.

"He keeps a great attitude and takes everything in stride," he added.

Don Pincus is a retired U.S. Army Corps of Engineers lieutenant colonel who worked at the Office of the Chief of Engineers at the Pentagon. He said his seven-member family from Manassas, Va., needed a break from the hustle and bustle of the city. He and his wife, Lori, and Blake and his four sisters — Lauren, Lacey, Brooke and Lexus — found that break at Pinnacle Falls.

"It was quite relaxing," Don Pincus said. "It was a relief to get out there and enjoy the mountainside."

The Pincuses spent a lot of time outdoors — hiking, exploring waterfalls and playing sports. While indoors, they shot pool and competed in Xbox Connect and Wii video games.

"The kids had a ball," Don Pincus said.

The family also visited Hendersonville eateries, including Hot Dog World and TCBY Yogurt. The owners of TCBY, Roger and Linda Freed, have worked for several years with families that have children battling cancer.

"I will do anything I can do for the children and to put a smile on their faces," Linda Freed said.

The Pinnacle Falls house is Believe in Tomorrow's fifth respite property and the second to support military families with ill children. To date, the Henderson County home has hosted 26 families.

Several contributors, volunteers and community supporters constructed the 3,300-square-foot home and continue its upkeep. Debbie Walsh of Hendersonville has volunteered with Believe in Tomorrow since 2007 and prepares the home for incoming families.

"What they (the foundation) do is such a great story," she said.

Inside, Walsh ensures everything is in place and ready for the families.

"Every time I come here, I think about the families that come here to relax and enjoy themselves," she said.

And the organization plans to have plenty more families visit the mountain getaway. Believe in Tomorrow will stay committed to serving the needs of military families, said Brian Morrison, founder and CEO.

"We are thrilled to be able to expand our military respite housing initiative to this area of the country and are eager to host many more families as they cross the threshold of the Believe in Tomorrow House at Pinnacle Falls," Morrison said.

Reach Schulman at 828-694-7890 or mark.schulman@blueridgenow.com.

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Bad breath being used in Stem Cell research

February 28th, 2012 5:26 am

SALT LAKE CITY — Researchers may have found a use for the chemical that causes the stench in bad breath, stink bombs, and flatulence.

This smelly substance known as Hydrogen Sulphide has been used in helping to convert stem cells from human teeth into liver cells.

The scientists conducting the investigation and research in the Journal of Breath Research claim that the gas increased the purity of the stem cells. The goal is that the liver cells produced from the stem cells could be used for repair if the organ was damaged.

Hydrogen Sulphide is produced by bacteria, and is toxic in large amounts. A group in China has reportedly tested the gas on rats to enhance the survival of mesenchymal stem cells taken from the bone marrow.

Researchers from the Nippon Dental University were investigating stem cells from dental pulp — the material in the middle of the tooth. The dental pulp was taken from patients undergoing a routine tooth extraction.

Dr. Ken Yaegaki, the lead author of the study, told the BBC why the dental pulp was so effective. "High purity means there are less 'wrong cells' that are being differentiated to other tissues, or remaining as stem cells," said Yaegaki.

However, one of the concerns with dental pulp as a source of stem cells is the limited number that can be harvested. The study did not say how many stem cells were actually produced.

But researchers are optimistic about the results, and the safety of the procedure.

"Until now, nobody has produced the protocol to regenerate such a huge number of hepatic cells for human transplantation," said Yaegaki. "Compared to the traditional method of using fetal bovine serum to produce the cells, our method is productive and, most importantly, safe."

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Bad breath being used in Stem Cell research

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Dental pulp stem cells transformed by 'bad breath’ chemical

February 28th, 2012 5:26 am

ScienceDaily (Feb. 26, 2012) — Japanese scientists have found that the odorous compound responsible for halitosis -- otherwise known as bad breath -- is ideal for harvesting stem cells taken from human dental pulp.

In a study published 27 February, in IOP Publishing's Journal of Breath Research, researchers showed that hydrogen sulphide (H2S) increased the ability of adult stem cells to differentiate into hepatic (liver) cells, furthering their reputation as a reliable source for future liver-cell therapy.

This is the first time that liver cells have been produced from human dental pulp and, even more impressively, have been produced in high numbers of high purity. "High purity means there are less 'wrong cells' that are being differentiated to other tissues, or remaining as stem cells. Moreover, these facts suggest that patients undergoing transplantation with the hepatic cells may have almost no possibility of developing teratomas or cancers, as can be the case when using bone marrow stem cells," said lead author of the study Dr. Ken Yaegaki.

The remarkable transforming ability of stem cells has led to significant focus from research groups around the world and given rise to expectations of cures for numerable diseases, including Parkinson's and Alzheimer's.

In this study, Dr. Ken Yaegaki and his group, from Nippon Dental University, Japan, used stem cells from dental pulp -- the central part of the tooth made up of connective tissue and cells -- which were obtained from the teeth of dental patients who were undergoing routine tooth extractions.

Once the cells were sufficiently prepared, they were separated into two batches (a test and a control) and the test cells incubated in a H2S chamber. They were harvested and analysed after 3, 6 and 9 days to see if the cells had successfully transformed into liver cells. To test if the cells successfully differentiated under the influence of H2S, the researchers carried out a series of tests looking at features that were characteristic of liver cells.

In addition to physical observations under the microscope, the researchers investigated the cell's ability to store glycogen and then recorded the amount of urea contained in the cell. "Until now, nobody has produced the protocol to regenerate such a huge number of hepatic cells for human transplantation. Compared to the traditional method of using fetal bovine serum to produce the cells, our method is productive and, most importantly, safe" continued Dr. Yaegaki.

Hydrogen sulphide (H2S) has the characteristic smell of rotten eggs and is produced throughout the body in the tissues. Although its exact function is unknown, researchers have been led to believe that it plays a key role in many physiological processes and disease states.

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Journal Reference:

Nikolay Ishkitiev, Bogdan Calenic, Izumi Aoyama, Hisataka Ii, Ken Yaegaki, Toshio Imai. Hydrogen sulfide increases hepatic differentiation in tooth-pulp stem cells. Journal of Breath Research, 2012; 6 (1): 017103 DOI: 10.1088/1752-7155/6/1/017103

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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Stem Cells and Medicine: Be Your Own Guinea Pig – Video

February 28th, 2012 4:13 am

23-02-2012 19:48 Complete video at fora.tv Dr. Bruce Conklin, Senior Investigator at the Gladstone Institute of Cardiovascular Disease, discusses the potential applications of stem cells in personalized medicine. By introducing a set of genes called the "Yamanaka factors," a simple skin sample can be transformed into something as complex as functioning heart tissue -- which could potentially be used to completely personalize medical testing. ---- Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. In many tissues, they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive. San Francisco's Gladstone Institutes is a leading force in stem cell research. In this presentation, Gladstone Investigator Dr. Bruce Conklin explains the surprising past, present, and future of stem cells.

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Stem cells put women on fertile ground – by Nature Video – Video

February 28th, 2012 4:13 am

24-02-2012 16:02 Stem cells from the ovaries of reproductive age women can give rise to cells that appear to be mature oocytes, suggesting that women can produce more eggs than the batch they are born with. The findings, reported in the March 2012 issue of Nature Medicine, open the door to a new generation of assisted fertility treatments. http://www.nature.com

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Stem Cells Might Have the Potential to Produce New Eggs

February 28th, 2012 4:13 am

Scientists might have found a way for a woman to be able to produce more eggs, potentially aiding and extending her fertility. The study, published in the journal Nature Medicine, found the ovaries of young women might still contain egg-producing stem cells, according to a report by MSNBC.

How could these stem cells potentially be used?

Theoretically, they could be used to develop new treatments for women who are struggling with infertility issues. The lead researcher on the study, Jonathan Tilly, has said that the stem cells could potentially be used to preserve the fertility of younger women who have struggled with serious diseases, like cancer, that may require harsh treatments that destroy the viability of their available eggs. He also speculated that they may be able to be used to restore egg production for an older woman that is no longer fertile.

What did the study involve?

Tilly, who works through Harvard-affiliated Massachusetts General Hospital, had first discovered these stem cells in mice. He then went looking for them in donated ovaries that he acquired through a partnership with a Japanese hospital.

The stem cells had to be isolated in order for Tilly to test them for their ability to produce new eggs. After being injected with a gene that would change them to a particular color, the stem cells were placed in part of a human ovary and grafted under the skin of mice to monitor the effect, according to My Health News Daily. The grafted stem cells did in fact appear to begin to grow new, albeit immature, eggs.

What are the potential challenges facing this study?

Mostly, skepticism. Some experts that have reviewed the study, including Dr. Mario Conti of the Center for Reproductive Sciences at the University of California, San Francisco, have pointed out that Tilly has failed to prove that these cells can be used to grow eggs in humans rather than mice. Other criticism concerns the stem cells themselves, which appear to make up a very small amount of the cells of the ovaries, and whether or not they are capable of producing a mature egg that can be fertilized and grow into a human being.

What are the next research steps?

Tilly plans on conducting more studies to test the potential of these stem cells. WebMD reported that he has already partnered with cell biologist Dr. Evelyn Telfer at the University of Edinburgh in Scotland to begin developing techniques to take the immature, or "seed" eggs and encourage them to become fully-mature eggs which may be able to be used.

Tilly and others have cautioned that his research is just the first step in a long journey. Any practical application for his research is still years away.

Vanessa Evans is a musician and freelance writer based in Michigan, with a lifelong interest in health and nutrition issues.

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Study: Stem cells in ovaries may grow new eggs

February 28th, 2012 4:13 am

(CBS/AP) Stem cells in young women's ovaries are capable of producing new eggs, according to a new study. The findings challenge 60 years of dogma that women are born with all the eggs they'll ever have.

PICTURES: Human eggs: 9 fascinating facts

For the study, published in the Feb. 26 issue of Nature Medicine and led by Jonathan Tilly of Massachusetts General Hospital, researchers examined healthy human ovaries donated by 20-something Japanese women who were undergoing a sex-change operation. The researchers fished out stem cells by searching for a protein found only on the surface of stem cells. The researchers then injected those stem cells into pieces of human ovary, transplanting the tissue under the skin of mice, to provide the tissue with a nourishing blood supply.

What happened? New egg cells formed within two weeks.

That's still a long way from showing they'll mature into usable, quality eggs, David Albertini, director of the University of Kansas' Center for Reproductive Sciences, cautioned.

Still, these findings could lead to better treatments for women left infertile because of disease - or simply because they're getting older.

"Our current views of ovarian aging are incomplete. There's much more to the story than simply the trickling away of a fixed pool of eggs," Tilly, who has long hunted these cells in a series of controversial studies, said.

Tilly's previous work has drawn skepticism, and independent experts urged caution about the latest findings, so the next step is to see whether other laboratories can verify the work. If the findings are confirmed, then it would take years of additional research to learn how to use the cells, Teresa Woodruff, fertility preservation chief at Northwestern University's Feinberg School of Medicine, said.

"This is experimental," Dr. Avner Hershlag, chief of the Center for Human Reproduction at North Shore-LIJ Health System in Manhasset, N.Y., told HealthDay. He said the study is "exciting" but emphasized the work is still very preliminary. "This is a beginning of perhaps something that could bring in new opportunities, but it's going to be a long time in my estimation until clinically we'll be able to actually have human eggs created from stem cells that make babies."

Still, even a leading critic said such research may help dispel some of the enduring mystery surrounding how human eggs are born and mature.

"This is going to spark renewed interest, and more than anything else it's giving us some new directions to work in," Albertini said. While he has plenty of questions about the latest work, "I'm less skeptical," he said.

Scientists have long taught that all female mammals are born with a finite supply of egg cells, called ooctyes, that runs out in middle age. Tilly, Mass General's reproductive biology director, first challenged that notion in 2004, reporting that the ovaries of adult mice harbor some egg-producing stem cells. Recently, Tilly noted, a lab in China and another in the U.S. also have reported finding those rare cells in mice.

More work is needed to tell exactly what these cells are, cautioned reproductive biologist Kyle Orwig of the University of Pittsburgh Medical Center, who has watched Tilly's work with great interest.

But if they're really competent stem cells, Orwig asked, then why would women undergo menopause? Indeed, something so rare wouldn't contribute much to a woman's natural reproductive capacity, added Northwestern's Woodruff.

Tilly argues that using stem cells to grow eggs in lab dishes might one day help preserve cancer patients' fertility. Today, Woodruff's lab and others freeze pieces of girls' ovaries before they undergo fertility-destroying chemotherapy or radiation. They're studying how to coax the immature eggs inside to mature so they could be used for in vitro fertilization years later when the girls are grown. If that eventually works, Tilly says stem cells might offer a better egg supply.

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Egg-making stem cells found in adult ovaries

February 28th, 2012 4:13 am

It’s time to rewrite the textbooks. For 60 years, everyone from high-school biology teachers to top fertility specialists has been operating under the assumption that women are born with all the eggs they will ever produce, with no way to replenish that supply. But the discovery of human egg-producing stem cells, harvested from the ovaries of six women aged 22 to 33, puts that dogma in doubt.

The work, published online in Nature Medicine1 by Jonathan Tilly and colleagues at Massachusetts General Hospital in Boston, parallels the findings of a Shanghai-based group2 that isolated similar stem cells from mice in 2009. However, both this and Tilly’s earlier work in mice3 remained controversial, with many experts sceptical that such stem cells existed.

“This is unequivocal proof that not only was the mouse biology correct, but what we proposed eight years ago was also correct — that there was a human population of stem cells in young adult tissue,” says Tilly.

To address the doubts, Tilly’s team began by developing a more sensitive method for identifying and collecting mouse ovarian stem cells. Their method, based on a technique called fluorescence-activated cell sorting (FACS), attaches a fluorescently labelled antibody to a protein, Ddx4, that is present on the outer surface of the stem cells but not on the surface of the later-stage egg cells or oocytes. The FACS instrument lines up cells in single file and sorts them one by one, separating the labelled ones from the rest; it also gets rid of dead or damaged cells, such as oocytes, in which internal Ddx4 might become accessible to the antibody. This method is more selective than previous isolation methods, which did not get rid of such cells.

Once the team confirmed that it had isolated mouse ovarian stem cells by this method, it set its sights on reproductive-age human ovaries. Yasushi Takai, a former research fellow in Tilly’s lab and now a reproductive biologist at Saitama Medical University in Japan, supplied frozen whole ovaries removed from sex-reassignment patients, all young women of reproductive age. “It was 9 November when we did the first human FACS sort and I knew immediately that it had worked,” says Tilly. “I cannot even put into words the excitement — and, to some degree, the relief — I felt.”

The cells they pulled out, called oogonial stem cells (OSCs), spontaneously generated apparently normal immature oocytes when cultured in the lab. To look at the development of the putative human OSCs in a more natural environment, the team labelled the cells with green fluorescent protein to make them traceable, and injected them into fragments ofadulthumanovarian tissue, which were then transplanted under the skin of mice. After one to two weeks of growth, the OSCs had formed green-glowing cells that looked like oocytes and that also expressed two of the genetic hallmarks of this cell type.

“There’s no confirmation that we have baby-making eggs yet, but every other indication is that these cells are the real deal — bona fide oocyte precursor cells,” says Tilly. The next step, to test whether the human OSC-derived oocytes can be fertilized and form an early embryo, will require special considerations — namely, private funding to support the work in the United States (federal funding cannot by law be used for any research that will result in the destruction of a human embryo, whatever the source of the embryo) or a licence from the UK Human Fertilisation and Embryology Authority to do the work with collaborators in the United Kingdom.

“I’ve seen these cells and how they behave. They’re convincing and impressive.”

Evelyn Telfer, a reproductive biologist at the University of Edinburgh, UK, was once sceptical of the mouse work, but has become a believer. “I’ve visited [Tilly’s] lab, seen these cells and how they behave. They’re convincing and impressive,” she says. Telfer, who studies the maturation of human eggs in vitro, will work with Tilly to try to grow the OSC-derived eggs to the point at which they are ready for fertilization.

She notes that there’s still no evidence that the OSCs form new eggs naturally in the body. However, if they could be coaxed in a dish to make eggs that could successfully be used for in vitro fertilization (IVF), it would change the face of assisted reproduction.

“That’s a huge ‘if’,” admits Tilly. But, he continues, it could mean an unlimited supply of eggs for women who have ovarian tissue that still hosts OSCs. This group could include cancer patients who have undergone sterilizing chemotherapy, women who have gone through premature menopause, or even those experiencing normal ageing. Tilly says that follow-up studies have confirmed that OSCs exist in the ovaries of women well into their 40s.

In addition, growing eggs from OSCs in the lab would allow scientists to screen for hormones or drugs that might reinvigorate these cells to keep producing eggs in the body and slow down women’s biological clocks. “Even if you could gain an additional five years of ovarian function, that would cover most women affected by IVF,” notes Tilly.

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Stem cells in ovaries can produce healthy eggs

February 28th, 2012 4:13 am

WASHINGTON — For 60 years, doctors have believed women were born with all the eggs they'll ever have. Now Harvard scientists are challenging that dogma, saying they've discovered the ovaries of young women harbor very rare stem cells capable of producing new eggs.

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If Sunday's report is confirmed, harnessing those stem cells might one day lead to better treatments for women left infertile because of disease — or simply because they're getting older.

"Our current views of ovarian aging are incomplete. There's much more to the story than simply the trickling away of a fixed pool of eggs," said lead researcher Jonathan Tilly of Harvard's Massachusetts General Hospital, who has long hunted these cells in a series of controversial studies.

Tilly's previous work drew fierce skepticism, and independent experts urged caution about the latest findings.

A key next step is to see whether other laboratories can verify the work. If so, then it would take years of additional research to learn how to use the cells, said Teresa Woodruff, fertility preservation chief at Northwestern University's Feinberg School of Medicine.

Still, even a leading critic said such research may help dispel some of the enduring mystery surrounding how human eggs are born and mature.

"This is going to spark renewed interest, and more than anything else it's giving us some new directions to work in," said David Albertini, director of the University of Kansas' Center for Reproductive Sciences. While he has plenty of questions about the latest work, "I'm less skeptical," he said.

Scientists have long taught that all female mammals are born with a finite supply of egg cells, called ooctyes, that runs out in middle age. Tilly, Mass General's reproductive biology director, first challenged that notion in 2004, reporting that the ovaries of adult mice harbor some egg-producing stem cells. Recently, Tilly noted, a lab in China and another in the U.S. also have reported finding those rare cells in mice.

But do they exist in women? Enter the new work, reported in the journal Nature Medicine.

First Tilly had to find healthy human ovaries to study. He collaborated with scientists at Japan's Saitama Medical University, who were freezing ovaries donated for research by healthy 20-somethings who underwent a sex-change operation.

Tilly also had to address a criticism: How to tell if he was finding true stem cells or just very immature eggs. His team latched onto a protein believed to sit on the surface of only those purported stem cells and fished them out. To track what happened next, the researchers inserted a gene that makes some jellyfish glow green into those cells. If the cells made eggs, those would glow, too.

"Bang, it worked — cells popped right out" of the human tissue, Tilly said.

Researchers watched through a microscope as new eggs grew in a lab dish. Then came the pivotal experiment: They injected the stem cells into pieces of human ovary. They transplanted the human tissue under the skin of mice, to provide it a nourishing blood supply. Within two weeks, they reported telltale green-tinged egg cells forming.

That's still a long way from showing they'll mature into usable, quality eggs, Albertini said.

And more work is needed to tell exactly what these cells are, cautioned reproductive biologist Kyle Orwig of the University of Pittsburgh Medical Center, who has watched Tilly's work with great interest.

But if they're really competent stem cells, Orwig asked, then why would women undergo menopause? Indeed, something so rare wouldn't contribute much to a woman's natural reproductive capacity, added Northwestern's Woodruff.

Tilly argues that using stem cells to grow eggs in lab dishes might one day help preserve cancer patients' fertility. Today, Woodruff's lab and others freeze pieces of girls' ovaries before they undergo fertility-destroying chemotherapy or radiation. They're studying how to coax the immature eggs inside to mature so they could be used for in vitro fertilization years later when the girls are grown. If that eventually works, Tilly says stem cells might offer a better egg supply.

Further down the road, he wonders if it also might be possible to recharge an aging woman's ovaries.

The new research was funded largely by the National Institutes of Health. Tilly co-founded a company, OvaScience Inc., to try to develop the findings into fertility treatments.

Copyright 2012 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

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