Stem Cell Clinic

Seminar to focus on stem cell research development

The latest discoveries and promises of stem cell research and the development of new therapeutic approaches for a variety of diseases will be in focus at the Qatar International Conference on Stem Cell Science and Policy 2012 which begins today.
The four-day event, being held at Qatar National Convention Centre, is a milestone in Qatar Foundation’s ongoing collaboration with the James A Baker III Institute for Public Policy at Rice University, Houston, Texas, US.
The aim of QF’s joint initiative with the Baker Institute’s International Programme on Stem Cell Science Policy is to develop stem cell research in Qatar as well as to find ways to address the shared challenges of community support for stem cell research in Doha and Houston.
To accomplish this goal, the programme has supported several events since its inception, including meetings, workshops, and training programmes in both cities.
The conference, which brings together eminent international as well as regional scientists, ethicists and policymakers, will also present the developed policy options that account for cultural, ethical and religious factors.
The event will draw attention to Qatar’s position in the development of stem cell research in the region and the world, given that research on stem cell as a national priority has already been initiated in the country’s best research institutions.
The conference objectives are to raise the awareness about Qatar’s initiative in promoting stem cell research, present the latest developments, and highlight the different religious views regarding stem cell research specifically the Islamic view.
The pros and cons of various options for regulating stem cell research and how scientists should address conflicting and confusing national policies and assess the different models of international collaboration will be discussed.
The conference also intends to interface with other institutions outside Qatar and contribute to the exchange of scientific knowledge to enhance the promotion of a scientific culture in the region and globally.
The keynote speakers are ambassador Edward P Djerejian (Baker Institute), Irving Weissman (Stanford University), Alan Trounson (president, California Institute for Regenerative Medicine), David Baltimore (president emeritus, Robert Andrews Millikan Professor of Biology, California Institute of Technology), Roger Pedersen (Department of Surgery, University of Cambridge) and Lawrence Corey (president and director, Fred Hutchinson Cancer Research Centre).
The conference, supported by Qatar Biomedical Research Institute, will also feature a number of invited speakers from across the world.

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Seminar to focus on stem cell research development

Bad breath used as stem cell tool

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."

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Bad breath used as stem cell tool

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

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

Massachusetts General researchers discover stem cell that makes eggs

By Carolyn Y. Johnson, Globe Staff

Massachusetts General Hospital researchers reported today they have discovered a rare stem cell in women’s ovaries that they hope one day might be used to make eggs, a claim already generating vigorous debate among scientists familiar with the research.

For decades, it has been thought that women are born with a finite supply of eggs, limiting their reproductive years. Doctors have sought ways of extending the fertility of women, especially as many wait later in life to begin having children.

The research, led by Jonathan Tilly of Mass. General and appearing in the journal Nature Medicine, opens the door to the possibility of taking tissue from a woman’s ovaries, harvesting stem cells from that tissue, and then creating eggs.

But scientists not involved with the Mass. General research said such an approach -- if it is even possible -- sits far in the future and will require considerably more work. Several scientists said Tilly, who co-founded a company focused on developing novel infertility treatments, had not yet made a convincing case that the stem cells he discovered can yield viable eggs, a critical first step.

Tilly has been a lightning rod in the field of fertility medicine since 2004, when he challenged the orthodoxy that women do not produce new eggs. In a research paper published that year, Tilly laid the foundation for the findings reported yesterday.

“There was a lot of backlash. It wasn’t surprising, given the magnitude of the paradigm shift that was being proposed -- this was one of the fundamental beliefs in our field,” Tilly said. “The subsequent eight years have been a long haul.”

In his new study, Tilly extended research by Chinese scientists published in 2009. He developed a technique that allowed scientists to sift out rare stem cells within the ovaries of mice that were tagged and implanted into the ovaries of normal mice. In the mouse ovaries, the stem cells produced eggs, which were removed and fertilized in a laboratory dish. They developed into embryos, although scientists did not use the embryos to produce mice.

Tilly and his team then wanted to know if such cells existed in humans, too.

The research team obtained ovarian tissue removed from young women undergoing sex change operations in Japan and performed the same experiment they’d done with the mouse ovaries. Much to their excitement, they discovered the rare, egg-producing cells in humans.

In later experiments, the human stem cells were used to produce cells that appeared to be eggs. In part because of ethical limitations, researchers were not able to show that the eggs could be used to create human embryos.

Tilly said that he has patented the stem cells and licensed the technology to OvaScience, the startup he co-founded.

Outside researchers described the findings as intriguing and provocative but also raised many questions. Scientists said it was still far from certain that the eggs created in the experiments could be used to produce babies. And they expressed concern that the findings could falsely inflate the hopes of women struggling with infertility.

Dr. David Keefe, chairman of obstetrics and gynecology at New York University Langone Medical Center, said he and other clinicians who see patients would like more than anything to have greater options for women to overcome infertility. But he said the Mass. General researcher had a history of leaping ahead from basic research findings to suggest clinical possibilities.

“Those of us who take care of patients are extremely protective of their hopes,” Keefe said. He noted that a few years ago, he saw half-a-dozen patients who wanted to delay their fertility decisions because of earlier research at Mass. General.

Even if the new findings are immediately replicated in labs around the world, Keefe said, “it’s so far from being clinical that it’s predatory to not be circumspect about it. Humility is an absolute requirement in this field. You’re dealing with people’s hopes and dreams.”

A 2005 study led by Tilly and done in mice suggested bone marrow transplants might offer a way to restore fertility. A year later, a separate group of Harvard researchers showed that this was unlikely to be true. Tilly himself no longer believes this is a way to restore fertility.

“The big difference in that work, now in retrospect, is these non-ovarian sources [of stem cells] don’t appear to do the job,” he said.

Tilly’s work in the past has divided researchers and failed to persuade many in the field that his interpretations are correct.

“We’ve not really been able to repeat his work, as a field,” said Teresa Woodruff, a professor of obstetrics and gynecology at the Feinberg School of Medicine at Northwestern University, who said she had already drawn up a chart of the claims made in the paper, the evidence to support those claims, and the questions they raise. Still, she said, “I do think he’s pushing the envelope in a way that does push all of us to think more broadly.”

Evelyn Telfer, a cell biologist at the University of Edinburgh, who criticized some of Tilly’s earlier work, said she is excited about the new findings. Tilly said that next month, he will fly to Scotland to begin a collaboration with Telfer.

“What he’s saying is we can get these cells,” Telfer said, “and I think it’s pretty convincing.”

The new paper doesn’t offer evidence that such stem cells are active in the ovary, supplying eggs during a woman’s lifetime. But the powerful cells could provide new insights into the important and poorly understood process in biology of egg-formation and allow scientists to look for drugs that might increase the activities of these stem cells, in order to overcome fertility problems.

Skeptics and supporters agreed on one thing: much work lies ahead.

“That’s science,” said Hugh Clarke, a professor in the department of obstetrics and gynecology at McGill University. “Of course, dogma should be challenged, but we shouldn’t assume dogma has been overturned based on a single report.”

Carolyn Y. Johnson can be reached at cjohnson@globe.com. Follow her on Twitter @carolynyjohnson.

Read the original:
Massachusetts General researchers discover stem cell that makes eggs

Stem Cell Finding Could Expand Women's Lifetime Supply of Eggs

SUNDAY, Feb. 26 (HealthDay News) -- Researchers report that they've isolated stem cells from adult human ovaries that can mature into eggs that may be capable of fertilization.

The lab findings, which upend longstanding scientific theory, could potentially lead to new reproductive technologies and possibly extend the years of a woman's fertility.

It was long believed that women were born with a lifetime supply of eggs, which was depleted by menopause. But a growing body of research -- including a new paper from Massachusetts General Hospital -- suggests egg production may continue into adulthood. The study is published in the March issue of Nature Medicine.

"Fifty years of thinking, in every aspect of experiments, of interpreting the results, and of the clinical management of ovarian function and fertility in women was dictated by one simple belief that turns out to be incorrect," said lead study author Jonathan Tilly, director of the hospital's Vincent Center for Reproductive Biology. "That belief was the egg cell pool endowed at birth is a fixed entity that cannot be renewed."

Dr. Avner Hershlag, chief of the Center for Human Reproduction at North Shore-LIJ Health System in Manhasset, N.Y., said the study is "exciting" but emphasized the work is still very preliminary.

"This is experimental," Hershlag said. "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."

The same team at Mass General caused a stir in 2004 when it published a paper in Nature reporting that female mice retain the ability to make new egg cells well into adulthood.

In both mice and humans, the vast majority of egg cells die through a process called programmed cell death, or apoptosis, the body's way of eliminating unneeded or damaged cells. For humans, that process is dramatic. Female fetuses have about 6 to 7 million eggs at about 20 weeks' gestation, a little more than 1 million at birth, and about 300,000 by puberty.

Studying mice egg cells and follicles, the tiny sacs in which stem cells become eggs, the Mass General researchers discovered something that didn't make mathematical sense.

Most prior research had focused on counting the healthy eggs in the ovaries, and then made assumptions about how many had died from that, Tilly said. But his lab looked at it the opposite way and focused on cell death.

"We found far too many eggs were dying than could be accounted for by the net change in the healthy egg pool," Tilly said. "We reasoned that maybe the field had missed something." They wondered if stem, or precursor cells, were repopulating the ovaries with new eggs.

Initially, the findings were met with skepticism, according to the study authors, but subsequent research bolstered the conclusions.

Those included a 2009 study from a team in China, published in Nature Cell Biology, that isolated, purified and cultured egg stem cells from adult mice, and subsequently introduced them into mice ovaries that were rendered infertile. The infertile mice eventually produced mature oocytes that were fertilized and developed into healthy baby mice.

Studies showing that women had the same capacity as mice were lacking, however.

In this study, Tilly's team used tissue from Japanese women in their 20s and 30s with gender identity disorder, who had their ovaries removed as part of gender reassignment surgery.

The researchers isolated the egg precursor cells and inserted into them a gene from a jellyfish that glows green, then inserted the treated cells into biopsied human ovarian tissue. They then transplanted the human tissue into mice. The green fluorescence allowed researchers to see that the stem cells generated new egg cells.

Tilly said the process makes evolutionary sense. "If you look at this from an evolutionary perspective, males have sperm stem cells that continually make sperm. Because species propagation is so important, we want to make sure it's the best sperm, so don't want sperm sitting around for 60 years waiting to get used," he said. It makes no sense from an evolutionary perspective that "females will be born with all the eggs they will have and let them sit there," he noted.

Hershlag, meanwhile, said much remains to be overcome.

"Ultimately, in our field only one thing counts," he said, "and that is if you can make an egg that can make a healthy baby."

More information

The U.S. National Library of Medicine has more on how human embryos develop.

Read more from the original source:
Stem Cell Finding Could Expand Women's Lifetime Supply of Eggs

First researcher joins The Jackson Lab for Genomic Medicine in Conn.

Bar Harbor – Yijun Ruan, Ph.D., an American geneticist who has pioneered new techniques to sequence and map DNA to better understand cancer growth and stem cell properties, will be the first scientist to join the new Jackson Laboratory for Genomic Medicine (JAX Genomic Medicine) in Farmington, Conn.

Ruan is currently associate director and senior group leader at the Genome Institute of Singapore and professor of biochemistry at the National University of Singapore. He is also an investigator with the Encyclopedia of DNA Elements (ENCODE) project, an international consortium of research groups funded by the National Human Genome Research Institute.
Ruan said he was attracted by The Jackson Laboratory’s famously collaborative research environment, and plans to “take a community approach to tackle genomic questions through intensive collaboration.” Through innovating new technologies and studying how the human and mouse genomes are regulated, he said his goal is to translate research findings into personalized medicine. Ruan has also been appointed director of JAX Genomic Sciences, and will be bringing his current research program and team with him to JAX Genomic Medicine.
JAX Genomic Medicine will unite doctors, patients, scientists and industry to find new ways to tailor disease diagnosis, prevention and treatment to each person’s unique genetic makeup, or genome. Ruan and other recruits will begin initial operations this year in leased space while a 173,000-square-foot permanent facility is designed and built. Construction will begin in 2013, and the new facility will open in 2014.
“Yijun’s broad interests in genome biology, coupled with his innovative approach to developing new research techniques, make him an ideal member of the new JAX Genomic Medicine research team,” said Bob Braun, Ph.D., Jackson’s associate director and chair of research.
After earning BS and MS degrees in microbiology from Huazhong Agricultural University in Wuhan, China, Ruan obtained his Ph.D. in plant molecular biology from the University of Maryland, College Park, where he also conducted postgraduate research. Following scientific appointments at Monsanto Co. in St. Louis and Large Scale Biology Corp. in Vacaville, Calif., Ruan was recruited to the Genome Institute of Singapore (GIS) in 2002. Edison Liu, M.D., former director of GIS and now president and CEO of The Jackson Laboratory, credits Ruan for building the institute’s state-of-the-art genomic technology platforms and its award-winning genome biology programs.
Ruan is an author of 70 research papers and holds patents in Japan, Singapore and the United Kingdom for the DNA analysis techniques he helped to develop. A U.S. citizen, Ruan is married and has two children.
In addition to recruiting research faculty, JAX Genomic Medicine is currently hiring a site director, science coordinator, senior human resources manager, facilities manager and senior financial analyst in Connecticut. Job announcements are on The Jackson Laboratory’s website at http://www.jax.org/careers/connecticut.html.
Braun notes that The Jackson Laboratory is expanding the research faculty at its headquarters campus in Bar Harbor, Maine, as well as recruiting faculty in Connecticut.
The Jackson Laboratory is an independent, nonprofit biomedical research institution and National Cancer Institute-designated Cancer Center based in Bar Harbor, Maine, with a facility in Sacramento, Calif., afuture institute in Farmington, Conn., and a total staff of about 1,400. Its mission is to discover the genetic basis for preventing, treating and curing human disease, and to enable research and education for the global biomedical community.

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First researcher joins The Jackson Lab for Genomic Medicine in Conn.