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.

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

Experts discuss stem cell banking ethics, policies By Noimot Olayiwola
Staff Reporter
Umbilical cord blood banking and transplantation, issues of ethics and policy as well as regulations governing stem cell banking were some of the high points of discussion during a session on ‘Stem Cell Banking’ at the Qatar International Conference on Stem Cells Science and Policy, underway at the Qatar National Convention Centre.
Sharing the Saudi Arabia experience on umbilical cord blood transplantation during a presentation, King Faisal Specialist Hospital and Research Centre’s blood bank (transfusion & donor services) director and of the Stem Cell Cord Blood Bank at the department of pathology and laboratory medicine, Dr Hind al-Humaidan, noted that the transplantation of allogeneic (taken from different individuals of the same species) bone marrow has been successfully used in the treatment of high risk or recurrent hematologic malignancies, bone marrow failure syndromes, selected hereditary immunodeficiency states and metabolic disorders.
“Early in the history of bone marrow transplantation, it was clear that access to a suitable donor was a major obstacle severely limiting the use of this potentially curative treatment modality. Although using an HLA (human leukocyte antigen) sibling donor is the best choice for transplantation, not all patients could have access to such a donor. Therefore transplant centres explored the possibility of using volunteer adult unrelated donors as an alternative to HLA–matched siblings,” she noted while mentioning that there was another alternative treatment strategy as a source of hematopoietic stem cell namely umbilical cord blood.
She explained that in Saudi Arabia, 60% of patients who need a transplant will find an HLA-matched sibling donor, leaving 40% of the patients in need of alternative sources.
The figure of donor with HLA-matched sibling elsewhere in the world is 45%, she said.
“The concept of establishing a cord blood bank in Saudi Arabia, under the umbrella of King Faisal Specialist Hospital and Research Centre, was raised after an increase in use of cord blood for transplantation due to the inability of finding fully or closely HLA-matched related donors. This non-profit public Cord Blood Bank is dedicated to making high quality cord blood units available to all patients in need of related and/or unrelated transplantation in Saudi Arabia and in the neighbouring countries through the development and maintenance of a centre of excellence for the collection, storage, search and distribution of ethnically and racially diverse cord blood units,” she said.
According to al-Humaidan, till date, the Cord Blood inventory consists of 3,725 units of high quality cord blood with a total of 70 cord blood transplants being carried out from the inventory.
Virgin Health Bank (VHB) chief executive officer Dr Rajan Jethwa discussed ways to make a cord blood bank attractive to users and how to ensure sustenance, especially when government funding of such facilities stops.
He described how VHB will become the magnet that will pull all stakeholders in the field of stem cell banking including researchers, technicians together towards achieving the establishment of a stem cell bank in Qatar.
Wake Forest School of Medicine’s Internal Medicine and Institute for Regenative Medicine Social Sciences and Health Policy professor Nancy King highlighted some of the ethical and policy issues governing stem cell banking globally while Field Fisher Waterhouse’s Public and Regulatory Law Group head Sarah Ellson shared some tips on ensuring regulations of biosamples. University of Central Lancashire’s Dr Katrina Aisha Choog spoke on informed consent among Arab Muslim research participants. The session was chaired by Harvard Stem Cell Institute’s executive director Brock Reeve.

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Experts discuss stem cell banking ethics, policies

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

In a new study, Harvard researchers say they have found stem cells in women that can be used to grow new eggs. Not surprisingly, this has raised much discussion about whether a woman’s biological clock can be stopped – why worry about running out of eggs if you can just make new ones whenever you  need them?

The work described in the paper, published online Sunday by the journal Nature Medicine, is still a long way from being useful to women in need of fertility treatments. And many scientists remain skeptical that these ovarian stem cells really can mature into healthy eggs.

But as long as we’re in the pie-in-the-sky realm, let’s consider another way that the ability to grow an abundant supply of eggs would be helpful: to make human embryonic stem cell lines that would be perfectly matched to patients.

This was a hot area of research in the middle of the last decade. While many scientists studied stem cells made from embryos that were no longer needed for fertility treatments, a smaller group was pursuing a derivation method called somatic cell nuclear transfer, or SCNT. It’s better known as “therapeutic cloning.”

Here’s the idea: You take an egg and remove all the DNA in the cell nucleus. Then you replace it with DNA from a patient. You give the egg an electric shock so it starts dividing and growing into an early-stage embryo.

But instead of implanting this embryo into a uterus and producing a baby that’s a genetic copy of another person, you would use it to make a line of human embryonic stem cells. Then you can use those stem cells to make replacement parts – new cardiac cells for patients who suffered heart attacks, for instance, or nerve cells that would replace those lost after a spinal cord injury. In theory, the new cells would work perfectly because they’d be a perfect genetic match. This is the vision of regenerative medicine.

For a few months back in 2005, it looked like this vision was on the verge of reality. South Korean researcher Hwang Woo Suk published a landmark paper in the journal Science in which he claimed to have made 11 lines of stem cells that were genetic matches to patients with Type 1 diabetes, spinal cord injuries and the so-called Bubble Boy disease. Scientists rejoiced, as did doctors and patients. But a few months later, Hwang was accused of faking the results. The study was retracted, and Hwang was prosecuted for embezzling research money and violating ethics laws.

Since then, researchers at Oregon Health & Sciences University have managed to clone monkey embryos in order to create embryonic stem cells. But in a 2007 study in the journal Nature, they said they had to use 304 eggs to make just two viable cell lines.

It’s hard to imagine how scientists would ever get their hands on 304 human eggs, especially since they generally aren’t allowed to pay women who might be willing to donate eggs for research purposes. It’s also not clear that a few hundred eggs would be enough to guarantee at least one line of stem cells. South Korean investigators eventually discovered that Hwang used 2,236 eggs in his studies that failed to produce a single embryo.

This is one of the major reasons why SCNT studies fell by the wayside. (For more on that, read this story from 2006.) But if there were a relatively simple way to grow hundreds – or thousands – of eggs in the lab, some scientists are confident they could create stem cells through therapeutic cloning.

If so, that would make the research at Harvard relevant to a whole lot of people besides women who hear their biological clocks ticking.

A summary of the Nature Medicine study is online here.

Return to the Booster Shots blog.

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Eggs made from stem cells could treat more than just fertility

February 27, 2012

Japanese scientists have recently discovered that hydrogen sulfide (H2S) – the chemical responsible for such malodorous phenomena as human flatulence, bad breath and rotten eggs – can be used to efficiently convert stem cells from human teeth into liver cells.

While the fetid chemical compound is produced in small quantities by the human body for use in a variety of biological signaling mechanisms, at high concentrations it is highly poisonous and extremely flammable.

A team of researchers at the Nippon Dental University in Tokyo collected stem cells from the teeth of patients undergoing extractions. The cells were harvested from the central part of the tooth known as the pulp which is made up predominantly of connective tissue and cells.

Stem cells recovered from the pulp were then divided into two groups and incubated in sealed chambers, one filled with hydrogen sulfide and the other a control group.

The cells from each chamber were then examined at three-day intervals to look for signs of transformation into liver cells. One such indicator is the ability to store glycogen, a compound that can be converted to glucose when the body needs energy.

According to a report of their findings that appeared this week in the Journal of Breath Research, the team was able to convert the stem cells to liver cells in relatively high numbers. And what’s more, said the team, H2S appears to help produce comparatively high quality, functional liver cells.

Lead researcher Ken Yaegaki explained that “[h]igh purity means there are less ‘wrong cells’ that are being differentiated to other tissues, or remaining as stem cells … These facts suggest that patients undergoing transplantation with the hepatic cells may have almost no possibility of developing teratomas (malignant tumors) or cancers.”

For the thousands of people around the world with chronic liver disease, this is a most welcome discovery, one that Yaegaki believes could potentially revolutionize this field of medicine.

“Until now, nobody has produced the protocol to regenerate such a huge number of hepatic cells for human transplantation,” added Yaegaki.

“Compared to the traditional method or suing fetal bovine serum to produce the cells, our method is productive and, most importantly, safe.”

Yaegaki’s hope is that his team’s discovery may eventually be fine-tuned to allow scientists to produce ample liver cells in a lab for use in repairing liver damage in human patients.

Moreover, this and similar studies in recent years have also gotten researchers in other fields questioning the possibilities for using hydrogen sulfide with other types of stem cells.

A team of researchers in China, for instance, recently reported using H2S to increase the survival rate of mesenchymal stem cells extracted from the bone marrow of rats.

—

On the Net:

Source: RedOrbit Staff & Wire Reports

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Researchers Use Noxious Gas To Convert Stem Cells To Liver Cells

NEW YORK & PETACH TIKVAH--(BUSINESS WIRE)--

BrainStorm Cell Therapeutics Inc. (OTCBB: BCLI.OB - News), a leading developer of adult stem cell technologies and therapeutics, announced today that the prestigious Nature Reviews Neurology, a Nature Publishing Group Journal, highlighted recently published preclinical research results indicating that stem cells, generated with Brainstorm’s NurOwn™ technology, provide hope for Huntington disease's patients.

In the preclinical studies conducted by leading scientists including Professors Melamed and Offen of Tel Aviv University and originally reported in Experimental Neurology, patients' bone marrow derived mesenchymal stem cells secreting neurotrophic factors (MSC-NTF) that were transplanted into an animal model of Huntington disease showed therapeutic benefits.

Addressing the role of these MSC-NTF cells in Huntington disease, Professor Daniel Offen explains, "the premise is that such cells can be transplanted safely into affected areas of the brain, and thereby serve as vehicles for delivering neurotrophic factors." Offen expressed his hope that this cell-based therapy may eventually progress to the clinic.

BrainStorm is currently conducting a Phase I/II Human Clinical Trial for Amyotrophic Lateral Sclerosis (ALS) also known as Lou Gehrig’s disease at the Hadassah Medical center. Initial results have shown that Brainstorm’s NurOwn™ therapy is safe, does not show any significant treatment-related adverse events, and have also shown certain signs of beneficial clinical effects.

Follow this link for the Research Highlights page in Nature Reviews Neurology (starts Feb. 28th ): http://www.nature.com/nrneurol/journal/vaop/ncurrent/index.html

To read the Original Article entitled ‘Mesenchymal stem cells induced to secrete neurotrophic factors attenuate quinolinic acid toxicity: A potential therapy for Huntington's disease’ by Sadan et al. follow this link: http://www.sciencedirect.com/science/article/pii/S0014488612000295

About BrainStorm Cell Therapeutics, Inc.

BrainStorm Cell Therapeutics Inc. is a biotech company developing adult stem cell therapeutic products, derived from autologous (self) bone marrow cells, for the treatment of neurodegenerative diseases. The company, through its wholly owned subsidiary Brainstorm Cell Therapeutics Ltd., holds rights to develop and commercialize the technology through an exclusive, worldwide licensing agreement with Ramot (www.ramot.org) at Tel Aviv University Ltd., the technology transfer company of Tel-Aviv University. The technology is currently in a Phase I/II clinical trials for ALS in Israel.

Safe Harbor Statement

Statements in this announcement other than historical data and information constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements, including, inter alia, regarding safety and efficacy in its human clinical trials and thereafter; the Company's ability to progress any product candidates in pre-clinical or clinical trials; the scope, rate and progress of its pre-clinical trials and other research and development activities; the scope, rate and progress of clinical trials we commence; clinical trial results; safety and efficacy of the product even if the data from pre-clinical or clinical trials is positive; uncertainties relating to clinical trials; risks relating to the commercialization, if any, of our proposed product candidates; dependence on the efforts of third parties; failure by us to secure and maintain relationships with collaborators; dependence on intellectual property; competition for clinical resources and patient enrollment from drug candidates in development by other companies with greater resources and visibility, and risks that we may lack the financial resources and access to capital to fund our operations. The potential risks and uncertainties include risks associated with BrainStorm's limited operating history, history of losses; minimal working capital, dependence on its license to Ramot's technology; ability to adequately protect its technology; dependence on key executives and on its scientific consultants; ability to obtain required regulatory approvals; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at http://www.sec.gov. The Company does not undertake any obligation to update forward-looking statements made by us.

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Nature: BrainStorm's NurOwn™ Stem Cell Technology Offers Hope for Treating Huntington Disease

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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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

Note: If no author is given, the source is cited instead.

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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Dental pulp stem cells transformed by 'bad breath’ chemical

An experiment that has produced human eggs from stem cells could be a boon for women desperate to have a baby, scientists claim.

New research has swept away the belief women only have a limited stock of eggs and replaces it with the theory the supply is continuously replenished from precursor cells in the ovary.

'The prevailing dogma in our field for the better part of the last 50 or 60 years was that young girls at birth were given a bank account of eggs at birth that's not renewable,' says Jonathan Tilly, director of the Vincent Center for Reproductive Biology at Massachusetts General Hospital, who led the research.

'As they become mature and become a woman, they use those eggs up (and) the ovaries will fail when they enter menopause.'

Tilly first challenged the 'bank account' doctrine eight years ago, suggesting female mammals continue producing egg-making cells into adulthood rather than from a stock acquired at birth.

His theory ran into a firestorm.

Other scientists challenged the accuracy of his experiments or dismissed their conclusions as worthless, given they were only conducted on lab mice.

But Tilly says the new work not only confirms his controversial idea, it takes it further.

In it, his team isolated egg-producing stem cells in human ovaries and then coaxed them into developing oocytes, as eggs are called.

Building on a feat by Chinese scientists, they pinpointed the oocyte stem cells by using antibodies which latched onto a protein 'handle' located on the side of these cells.

The team tagged the stem cells with a fluorescent green protein - a common trick to help figure out what happens in lab experiments.

The cells were injected into biopsied human ovarian tissue which was then grafted beneath the skin of mice.

Within 14 days, the graft had produced a budding of oocytes. Some of the eggs glowed with the fluorescent tag, proving that they came from the stem cells. But others did not, which suggested they were already present in the tissue before the injection.

Tilly said 'the hairs were standing up on my arm' when he saw time-elapse video showing the eggs maturing in a lab dish.

Further testing needs to be done but Tilly says the work could be far-reaching.

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Human eggs produced from stem cells

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

Note: If no author is given, the source is cited instead.

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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Egg-producing stem cells isolated from adult human ovaries

(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.

Here is the original post:
Study: Stem cells in ovaries may grow new eggs

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 harbour very rare stem cells capable of producing new eggs.

If the 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 harbour 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 Sunday 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.

Egg quality questions

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 U.S. National Institutes of Health. Tilly co-founded a company, OvaScience Inc., to try to develop the findings into fertility treatments.

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Egg-producing stem cells found in women's ovaries

M I Walker / Getty Images

Are women born with all the eggs they'll ever have? Harvard scientists say possibly not. Their discovery of stem cells in human ovaries could someday help infertile women produce new eggs.

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.

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 Sunday 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.

The rest is here:
Rethinking Infertility: Study Shows Women Have Egg-Producing Stem Cells

Harvard scientists are challenging traditional medical logic that dictates that women are born with a finite amount of eggs.  The scientists said they have discovered the ovaries of young women harbor rare stem cells that are in fact capable of producing new eggs.

If properly harnessed, those stem cells may someday lead to new treatments for women suffering from infertility due to cancer or other diseases – or for those who are simply getting older, according to the researchers.  Lead researcher Jonathan Tilly of Harvard's Massachusetts General Hospital has co-founded a company, OvaScience Inc., to try to develop the findings into fertility treatments.

The idea that women are born with all the egg cells – called oocytes – they’ll ever have has been called into question by past research, which found egg-producing stem cells in adult mice.

In this latest study, Harvard researchers, in collaboration with Japanese scientists, used donated frozen ovaries from 20 year olds and ‘fished out’ the purported stem cells.  

The researchers inserted a gene into the stem cells, which caused them to glow green.  If the cells produced eggs, those would glow green, too.

The researchers first watched through a microscope as new eggs grew in a lab dish.  They then implanted the human tissue under the skin of mice to provide a nourishing blood supply.  Within two weeks, they observed green-tinged cells forming.

While the work of the Harvard scientists does show potential, there are still questions as to whether the cells are capable of growing into mature, usable eggs.

If so, researchers said, it might be possible one day to use the stem cells in order to grow eggs in lab dishes to help preserve cancer patients’ fertility, which can be harmed by chemotherapy.

Now, I just want to say, while this would be a remarkable discovery – if it pans out – I do have a few concerns. 

I think for specific patients in prime, childbearing ages, who are at risk of losing their fertility for one reason or another, this could be a fruitful discovery for them.

Be that as it may, I am totally against commercializing this technology to the point where women going through menopause look at this as another way of getting pregnant.  For many, this could create incredibly high-risk pregnancies, among other medical problems.

While science is capable of great discovery and innovation – particularly in the field of stem cells – I believe that with reproductive medicine, we should move forward with great caution to minimize any risk to mother and baby.

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Stem cell fertility treatments could be risky for older women

NEWARK, Calif., Feb. 27, 2012 (GLOBE NEWSWIRE) -- StemCells, Inc. (Nasdaq:STEM - News) today announced that it will participate in the Qatar International Conference on Stem Cell Science and Policy, which is being held in Qatar from February 27 to March 1, 2012. The Company, which is the leader in development of cell-based therapeutics for central nervous system disorders, was specifically invited by the conference's sponsors, the State of Qatar and Amir of Qatar His Highness Sheikh Hamad bin Khalifa Al-Thani, as well as the James A. Baker III Institute for Public Policy of Rice University, and is the only company to be invited.

Ann Tsukamoto, Ph.D., StemCells' Executive Vice President, Research and Development, will make a presentation on the clinical translation of human neural stem cells. StemCells was the first company to receive authorization from the US Food and Drug Administration to conduct a clinical trial of purified human neural stem cells, and the Company is currently conducting two clinical trials with a third anticipated to start later this year. Dr. Tsukamoto will also be the moderator of the panel session on neurological disorders, which is scheduled to be held on March 1 from 9:30 a.m. to 11:00 a.m. Arabian Standard Time (AST).

In addition, Irving Weissman, M.D., Chairman of StemCells' Scientific Advisory Board, will make a keynote presentation to the conference on Tuesday, February 28 at 9:00 a.m. AST. Dr. Weissman, who is Virginia and Daniel K. Ludwig Professor of Cancer Research, Professor of Pathology and Professor of Developmental Biology at the Stanford School of Medicine, and Director of the Stanford Institute of Stem Cell Biology and Regenerative Medicine, will speak on normal and neoplastic stem cells. Dr. Weissman will also participate in a panel discussion on the opportunities and challenges for stem cell research, and will moderate a panel discussion on pluripotent stem cells.

The Qatar International Conference on Stem Cell Science and Policy will bring together more than 400 international participants from industry, academia and public policy, including leading experts from each of these sectors. The conference's objectives are to showcase the latest stem cell research from around the world, while promoting discussion and awareness of scientific, ethical and regulatory issues related to this innovative and dynamic field.

About StemCells, Inc.

StemCells, Inc. is engaged in the research, development, and commercialization of cell-based therapeutics and tools for use in stem cell-based research and drug discovery. The Company's lead therapeutic product candidate, HuCNS-SC(R) cells (purified human neural stem cells), is currently in development as a potential treatment for a broad range of central nervous system disorders. The Company recently completed a clinical trial in Pelizaeus-Merzbacher disease (PMD), a fatal myelination disorder in children, and expects to report the trial results soon. The Company is also conducting a Phase I/II clinical trial in chronic spinal cord injury, and expects to initiate a Phase I/II clinical trial in dry age- related macular degeneration in the near future. In addition, the Company is pursuing preclinical studies of its HuCNS-SC cells in Alzheimer's disease. StemCells also markets stem cell research products, including media and reagents, under the SC Proven(R) brand, and is developing stem cell-based assay platforms for use in pharmaceutical research, drug discovery and drug development. Further information about StemCells is available at http://www.stemcellsinc.com.

The StemCells, Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=7014

Apart from statements of historical fact, the text of this press release constitutes forward-looking statements within the meaning of the U.S. securities laws, and is subject to the safe harbors created therein. These statements include, but are not limited to, statements regarding the clinical development of its HuCNS-SC cells; the Company's ability to commercialize drug discovery and drug development tools; and the future business operations of the Company. These forward-looking statements speak only as of the date of this news release. The Company does not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Such statements reflect management's current views and are based on certain assumptions that may or may not ultimately prove valid. The Company's actual results may vary materially from those contemplated in such forward-looking statements due to risks and uncertainties to which the Company is subject, including those described under the heading "Risk Factors" in the Company's Annual Report on Form 10-K for the year ended December 31, 2010 and in its subsequent reports on Form 10-Q and Form 8-K.

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StemCells, Inc. to Participate in Qatar International Conference on Stem Cell Science and Policy 2012

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’

Public release date: 26-Feb-2012
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital

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. Tilly is a co-founder of OvaScience, Inc. (www.ovascience.com), which has licensed the commercial potential of these and other patent-protected findings of the MGH-Vincent team for development of new fertility-enhancing procedures.

Massachusetts General Hospital (www.massgeneral.org), founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $750 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

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Mass. General researchers isolate egg-producing stem cells from adult human ovaries

27 February 2012 Last updated at 00:06 ET

Hydrogen sulphide, the gas famed for generating the stench in stink bombs, flatulence and bad breath, has been harnessed by stem cell researchers in Japan.

Their study, in the Journal of Breath Research, investigated using it to help convert stem cells from human teeth into liver cells.

The scientists claimed the gas increased the purity of the stem cells.

Small amounts of hydrogen sulphide are made by the body.

It is also produced by bacteria and is toxic in large quantities.

Therapy

A group in China has already reported using the gas to enhance the survival of mesenchymal stem cells taken from the bone marrow of rats.

Researchers at the Nippon Dental University were investigating stem cells from dental pulp - the bit in the middle of the tooth.

They said using the gas increased the proportion of stem cells which were converted to liver cells when used alongside other chemicals. The idea is that liver cells produced from stem cells could be used to repair the organ if it was damaged.

Dr Ken Yaegaki, from Nippon Dental University in Japan, said: "High purity means there are less 'wrong cells' that are being differentiated to other tissues, or remaining as stem cells."

One of the concerns with dental pulp as a source of stem cells is the number that can be harvested.

However, the study did not say how many cells were actually produced.

Prof Chris Mason, a specialist in regenerative medicine at University College London, said: "It would be interesting to see how hydrogen sulphide works with other cells types."

See more here:
Bad breath used as stem cell tool

Public release date: 26-Feb-2012
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Contact: Joe Winters
joseph.winters@iop.org
44-794-632-1473
Institute of Physics

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 today, Monday 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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From Monday 27 February, this paper can be downloaded from http://iopscience.org/1752-7163/6/1/017103

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Dental pulp stem cells transformed by 'bad breath' chemical

Washington, Feb 27 (ANI): The odorous compound responsible for halitosis - otherwise known as bad breath - may play a key role in harvesting stem cells taken from human dental pulp, a new study has suggested.

In the study, Japanese scientists 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. 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," Dr. Yaegaki added.

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.

The study has been published in IOP Publishing's Journal of Breath Research. (ANI)

Originally posted here:
'Bad breath' chemical may fuel development of dental pulp stem cells

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

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.

Mr. 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. Mr. 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, Mr. 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 Sunday in the journal Nature Medicine.

Mr. Tilly 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.

Mr. 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, Mr. 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 and transplanted the human tissue under the skin of mice. Within two weeks, they reported telltale green-tinged egg cells forming.

More work also is needed to tell exactly what these cells are and whether they’ll mature in usable eggs, cautioned reproductive biologist Kyle Orwig of the University of Pittsburgh Medical Center, who has watched Mr. Tilly’s work with great interest.

But if they’re really competent stem cells, Mr. 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 Ms. Woodruff.

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

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Report says women have egg-producing stem cells