StemCell Therapy

February 27, 2012, 12:41 AM EST

By Ryan Flinn

Feb. 27 (Bloomberg) -- Stem cells taken from human ovaries were used to produce early-stage eggs by scientists in Boston who may have created a new method to help infertile women.

Females have a fixed number of eggs from birth that are depleted by the time of menopause. The finding, published today in the journal Nature Medicine, challenges the belief that their ovaries can’t make more. The research was led by Jonathan Tilly, the director of Massachusetts General Hospital’s Vincent Center for Reproductive Biology.

Tilly reported in 2004 that ovarian stem cells in mice create new eggs, or oocytes, in a way similar to how stem cells in male testes produce sperm throughout a man’s life. His latest work, if reproduced, would suggest the same is true for human ovaries, potentially pointing at new ways to aid fertility by delaying when the ovaries stop functioning.

“The 50-year-old belief in our field wasn’t actually based on data proving it was impossible, or not ongoing,” Tilly said in a telephone interview. “It was simply an assumption made because there was no evidence indicating otherwise. We have human cells that can produce new oocytes.”

In the study, healthy ovaries were obtained from consenting patients undergoing sex reassignment surgery. The researchers were able to identify ovarian stem cells because they express a rare protein that’s only seen in reproductive cells.

The stem cells from the ovaries were injected into human ovarian tissue that was then grafted under the skin of mice, which provided the blood supply that enabled growth. Within two weeks, early stage human follicles with oocytes had formed.

7-Million Eggs

A female is most endowed with oocytes, or eggs, as a fetus, when she has about 7 million. That number that drops to 1 million by birth, and around 300,000 by puberty. By menopause, the number is zero. Since the 1950’s, scientists thought that ovarian stem cells capable of producing new eggs are only active during fetal development.

“This paper essentially opens the door to the ability to control oocyte development in human ovaries,” Tilly said.

About 10 percent of women of child-bearing age in the U.S., or 6.1 million, have difficulty getting pregnant or staying pregnant, according to the Centers for Disease Control and Prevention. Most cases of female infertility are caused by problems with ovulation, hormone imbalance or age.

The study by Tilley and his colleagues offers “a new model system for understanding the human egg cell,” said David F. Albertini, director of the Center for Reproductive Services and professor in the department of molecular and integrative physiology at Kansas University, in a telephone interview.

‘Practical Applications”

Still, “there’s a long way to go before this has real practical applications. I’ve spent 35 years of my life studying egg cells and this is a cell that is at least as complicated as a neuron in the brain, if not more,” Albertini said.

The work needs to be reproduced and expanded by other scientists “to make it into something that will make us confident the cells are safe to use and we could actually use them to repopulate an egg-depleted ovary,” he said.

Tilly’s team is exploring the development of an ovarian stem-cell bank that can be cryogenically frozen and thawed without damage, unlike human eggs, he said. The researchers are also working to identify hormones and other growth factors for accelerating production of eggs from human ovarian stem cells and ways to improve in-vitro fertilization.

“The problem we face with IVF is we don’t have many eggs to work with,” he said. “These cells are renewable. If we are successful -- and it’s a big if -- in generating functioning eggs from these cells, we can generate as many eggs as we need to on a per patient basis.”

Tilly is also collaborating with researchers at the University of Edinburgh in the U.K. to determine whether the oocytes can be developed into fully mature human eggs for fertilizing. The U.S bans creating or fertilizing embryos for experimental purposes, he said.

A company Tilly co-founded, Boston-based OvaScience Inc., has licensed the technology for potential commercial applications.

--With assistance from Sarah Frier in New York. Editors: Angela Zimm, Andrew Pollack

To contact the reporter on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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Ovarian Stem Cells Make Human Eggs in Possible Aid to Fertility

1:00 AM
If confirmed, harnessing such cells may lead to better treatments for women left infertile by disease or age.

The Associated Press

WASHINGTON - For 60 years, doctors have believed that women were born with all the eggs they'll ever have. Now Harvard scientists say they've found that the ovaries of young women harbor rare stem cells capable of producing new eggs.

FOR MORE

READ A SUMMARY of the report on how women's stem cells can be turned into eggs: tinyurl.com/6w6kass

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.

A next step is to see whether other laboratories can verify the work. If so, then it would take years of further study 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.

"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.

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 first challenged that notion in 2004, reporting that the ovaries of adult mice harbor some egg-producing stem cells.

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

Tilly collaborated with scientists at Japan's Saitama Medical University, who were freezing ovaries donated for study by healthy 20-somethings who underwent sex-change operations.

He had to figure out how to tell if he was finding true stem cells or just very immature eggs.

His team latched on to 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.

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Rare stem cells may produce new eggs, scientists say

20-02-2012 01:33 Many of our patients travel to Guangzhou from all over the world for medical treatment and tourism. China medical tourism can help with becoming a patient, travel arrangements and language assistance. If you want to know more about our services, please browse the web:htttp://www.medicaltourism.hk/ or mail to us: giels-x@medicaltourism.hk firstcare-china@hotmail.com Adult stem cells provide real improvement for cirrhosis patients Breakthrough adult stem cell research has shown that stem cells are able to regenerate and repair damaged or destroyed liver cells. For patients with cirrhosis, this means improved liver function, decreased pain and a significantly improved quality of life. Stem cell therapy offers the safest and most effective treatment alternative for liver cirrhosis and it is quickly becoming a preferred treatment in Asia. China medical tourism offers unique access to the best stem cell therapies available at leading medical facilities. Supporting data and statistics Three out of every four patients treated experienced a significant improvement in their condition following stem cell treatment. The following clinical results were observed: •Improved liver function •Decreased pain •Improved values for liver function, PLT (blood platelet) and blood ammonia You may see improvements during your hospitalization due to neurotrophic factors released during the stem cell transplantation, which stimulate nerve activity; new cells will grow for up to six months after you ...

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China medicdal tourism-- Cirrhosis--Stem cells therapy 3.mp4 - Video

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."

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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.

###

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

The compound that causes bad breath could help fuel the development of stem cells from dental pulp, according to a study.

Hydrogen sulphide (H2S) - which has the characteristic smell of rotten eggs - appears to help teeth stem cells transform into liver cells, which could prove a valuable treatment for patients, researchers found.

H2S is a major cause of halitosis or bad breath, which is of concern to millions of people worldwide.

A team of experts took stem cells from dental pulp - the central part of the tooth made up of connective tissue and cells - obtained from the teeth of dental patients undergoing routine tooth extractions.

The cells were separated into two groups, with one group incubated in a H2S chamber and the other group acting as a control. The cells were analysed after three, six and nine days to see if they had transformed into liver cells. Their ability to function as liver cells was also tested, including the ability to store glycogen and collect urea.

The study, published in the Journal of Breath Research, from the Institute of Physics, suggested liver cells could be produced in high numbers of high purity.

Lead author of the study, 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. Moreover, these facts suggest that patients undergoing transplantation with the hepatic (liver) cells may have almost no possibility of developing teratomas (tumours) or cancers.

"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."

Professor Anthony Hollander, head of cellular and molecular medicine at Bristol University, said much more research was needed.

He said: "This is interesting work in a new direction but there's a long way to go to see if it is usable therapeutically. This is potential evidence but the real test of the liver cell is whether it metabolises specific toxins," he said, adding that that requires enzyme function tests."

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Teeth 'transform into liver cells'

Discovery of stem cells in human ovaries overturns dogma

Web edition : Sunday, February 26th, 2012

A newly discovered type of stem cell in the ovary could mean big things for women’s health, possibly leading to new fertility treatments and maybe even a way to delay menopause.

Since the 1950s it has been thought that women are born with all of the egg cells they will ever have. But with the discovery of egg-producing stem cells in mice and humans, it now appears that the ovary can replenish its egg supply. Researchers led by Jonathan Tilly, a reproductive biologist at Massachusetts General Hospital in Boston, report the finding online February 26 in Nature Medicine.

Other researchers hail the discovery as a genuine breakthrough with huge implications. “This is like discovering a new planet in our solar system that has a bacterium on it,” says Kutluk Oktay, a reproductive biologist at the New York Medical College in Valhalla. At the very least, he says, the cells offer hope for extending a woman’s reproductive life span.

Tilly didn’t set out to overturn the accepted dogma that women don’t make new eggs. As part of their research into the onset of menopause, he and his colleagues developed ways to track the death of egg cells over time. When the researchers counted the number of healthy egg cells in mouse ovaries, they saw a steady decline with age as expected. But the team also found that dying cells greatly outnumber the starting population of eggs. “What we had was a math problem,” Tilly says. “We refocused all of our efforts on this glaring mathematical dilemma.”

In 2004, Tilly’s group reported the answer to their math problem: There are more dying eggs than healthy ones because stem cells in mouse ovaries are constantly making more eggs, which then die off. The discovery didn’t go over well. “The vast majority of our colleagues were not very receptive,” Tilly says. Many of those who did accept the existence of egg-forming stem cells in mice didn’t think humans would have similar cells.

Tilly and his colleagues isolated stem cells from ovaries that had been removed from six women during sex reassignment surgeries at Saitama Medical Center in Japan. Only about 1.5 percent of cells in the ovaries fit the stem cell profile. The researchers compiled molecular profiles of the cells and demonstrated that the stem cells are able to make precursors to eggs when transplanted into other ovaries. 

Tilly’s group convincingly demonstrates that stem cells in human ovaries can make egg cell precursors. But it remains to be seen if the cells can make mature gametes, says Evelyn Telfer, a reproductive biologist at the University of Edinburgh.

Stopping the depletion of eggs or keeping ovaries functioning could help stave off many of the health problems women experience after menopause, Tilly says. “If we can somehow control this biological clock, to me, the possibilities are endless.”

Found in: Genes & Cells

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Eggs may be made throughout adulthood

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

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.

More here:
Seminar to focus on stem cell research development

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.

Teresa Woodruff, a professor of obstetrics and gynecology at the Feinberg School of Medicine at Northwestern University 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.

See the rest here:
Massachusetts General researchers discover stem cell that makes 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 the original here:
Stem Cell Finding Could Expand Women's Lifetime Supply of Eggs

by: John Phillip

Researchers publishing in the Canadian Journal of Physiology and Pharmacology (CJPP) have found that a diet enhanced with vitamin and mineral supplementation can lower the risk of developing precancerous colon cancer lesions by up to 84%. Colon cancer is the second most common form of the disease affecting men and women in the US, with nearly 150,000 new diagnoses each year.

Nutrition experts and alternative practitioners understand that cancer is largely a disease caused by poor lifestyle behaviors including a diet lacking an optimal intake of vitamins and minerals. Chronic illnesses including colon cancer are the result of many years and decades of low nutritional status, as support for a healthy immune response is suppressed. Scientists now provide compelling evidence in support of whole-food based vitamin and mineral supplementation to dramatically lower the risk of colorectal cancer. Read more...

AyurGold for Healthy Blood

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Source: Data Sneak Peek: Groups Involved in Patient Adherence Teams

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http://microarray.wordpress.com/feed/

Via Scoop.it – inPharmatics

Companies on the forward edge are putting a heavy emphasis on digital in their commercial models — but how can mobile technologies assist pharmaceutical and biotech firms in this transition?   Tablets to support the sales force – While sales forces are shrinking, they still play a vital role in educating prescribers on new medications. The pharma industry, taking the lead of companies like GSK, is starting to incent sales reps based on quality of service versus amount of sales (read more here in the WSJ). One of the tools that is helping deliver better service is the tablet. Reps with an iPad can deliver more interactive and engaging product information, capture signatures for compliance and make the most of a few quick minutes with a doctor in the time it would take a laptop to boot up.   Online and mobile drug sampling programs – Companies now have the ability to leverage PDMA-compliant mobile apps and websites that allow physicians to request free product samples that they can distribute to their patients to gauge efficacy and assist with adherence. Because the Internet never sleeps, physicians can do this no matter what shifts they are working, independent of time zone or location, 24 hours a day.   Direct-to-HCP mobile advertising – It used to be that most online and mobile advertisements for drugs were placed only in industry magazines, blogs and online communities geared toward healthcare professionals and general consumer websites. We see this changing, with emergence of mobile networks focused on healthcare such as Tomorrow Networks, which is comprised of more than 50 medical apps. Pharma companies can now buy ad placements in mobile apps made exclusively for physicians and other healthcare professionals. A physician can be looking up treatment information at the point of care and see an ad for a medication that is relevant to their patient’s ailment. That’s incredibly powerful for the physician and advantageous for the advertiser.   mDetails – Physicians want to learn about the best drugs and treatments for their patients. mDetails are multimedia mobile product presentations that provide information about drugs in a way that allows physicians to absorb detailed information at their own pace — and in their own time. Because mDetails are distributed on smartphones – it lets physicians fit pharma product education into ‘found time’ at any point during their day that’s convenient for them.   By employing a multi-channel approach and by helping healthcare professionals do their jobs better instead of just selling to them, pharmaceutical companies can reach their target audiences and develop deeper value-based relationships. The aforementioned examples are just a few of the ways that pharmaceutical companies can leverage the ever-growing mobile channel; there are many more evolving every day.
Via http://www.mhimss.org

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Via Scoop.it – inPharmatics
UK Government launches G-Cloud store with 257 cloud computing suppliers. Offering the public sector around 1,700 cloud computing services for year-long contracts. The G-Cloud initiative, dubbed CloudStore, aims to bring a broader range of cloud computing suppliers to the government market and increase the flexibility in procurement contracts
Via http://www.govstore.net

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The $3 billion California stem cell agency, which is facing its possible demise in five years, is exploring an afterlife that dips into "venture philanthropy" on a national level as well as investment ties with Big Pharma.

The Golden State's unprecedented research program laid out those possibilities in a "transition plan" sent this week to Gov. Jerry Brown and the state legislature. The plan was required under a law passed two years ago. The agency's future direction was also aired at a meeting last month in Los Angeles.

The California Institute for Regenerative Medicine(CIRM) will run out of funds for new grants in 2017. Its only real source of funding is cash that the state borrows (bonds). CIRM says that only $864 million remains for new research awards, and some of its recent grant rounds exceed $200 million. The current position of the agency is that it is "premature" to consider asking voters in financially strapped California to approve another multi-billion dollar bond measure.

The venture philanthropy effort involves creation of a nonprofit organization. CIRM Chairman Jonathan Thomas said in January that he is "test-driving (the proposal) with some high net worth donors we know to be interested in the stem cell space." Thomas was addressing the Citizens Financial Accountability and Oversight Committee, the only state entity specified charged with overseeing the agency and its directors. He said,

"We're busily putting together in conjunction with a national organization called the Alliance for Regenerative Medicine the plans for a nonprofit venture philanthropy fund."

He said it would "would accept applications for awards from researchers and companies all over the country, not just those funded by CIRM, but those funded by NIH or the New York Stem Cell Foundation or the state of Maryland or whatever."

The Alliance for Regenerative Medicine is an industry-dominated lobbying group, based in Washington, D.C.  The group's executive director and co-founder is Michael Werner, a longtime pharma and health industry lobbyist, who is also a partner in the influential Washington law firm of Holland and Knight.

The "biopharma investment fund" proposed by CIRM is less well developed. CIRM said it plans to explore opportunities with companies to fund stem cell research in California. The transition document uses as an example an $85 million deal between Pfizer and UC San Francisco, which gives the company special access to biomedical research.

The transition plan also touches on other issues such as winding down grants after its new grant money runs out, along with protecting intellectual property.

The plan could be considered a marketing tool for the agency's afterlife efforts. The document devotes a good portion of its nine pages to recounting the history of CIRM and touting its accomplishments.

Thomas used the occasion of the submission of the plan as a springboard for a piece yesterday on the CIRM research blog.He concluded his item by quoting from the plan itself. CIRM's achievements during the past seven years, he wrote, "will allow California to continue world (stem cell) leadership in the coming decades."

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

With the $700,000 Institute of Medicine inquiry into the performance of the California stem cell agency half complete – at least publicly – the blue-ribbon panel seems to be coming up short on comments from outside of the agency itself.

The major public effort by the IOM to secure comments is the passive posting of forms to be filled out on the IOM web site.

How many responses has the IOM received on those forms? The IOM has not disclosed that information despite two inquiries earlier this month by the California Stem Cell Report.

The prestigious institute is undertaking the study of $3 billion agency under contract with CIRM, which is paying the IOM $700,000. Some CIRM directors have expressed hope that the IOM findings will help build support for another multi-billion dollar state bond measure to renew financing for CIRM. It is scheduled to run out of money for new grants in five years.

So far, the IOM panel has held two public meetings, one in Washington, D.C., and one in the San Francisco area. The final California hearing is scheduled for April 10 in Irvine with the last public meetings scheduled for later this year in Washington.

So far, the panel has heard only from CIRM employees or directors as well as researchers who have received tens of millions of dollars in CIRM grants. The IOM has not heard publicly from a single independent witness.

The IOM has posted on its web site forms seeking comments from the public, grant recipients, beneficiary institutions and businesses. However, passive postings of forms are unlikely to generate more than a relative handful of responses. To produce significant numbers requires aggressive and targeted follow-up.

It is also unclear exactly what the IOM is doing to seek information from biotech businesses and unsuccessful grant applicants. Some businesses have complained publicly about the tiny share of funding that industry has received. And some CIRM directors have expressed concern for several years about the inadequacies of business funding.

On Feb. 12, the California Stem Cell Report queried the IOM about its efforts at outreach, asking for specifics on what is being done. Christine Stencel, a spokeswoman for the IOM, replied,

"The IOM has been obtaining and compiling lists of organizations and people to circulate the questionnaires as widely as possible among target groups. For example, IOM has sent a notice to some 300 stakeholder groups encouraging participation."

Other specifics were not forthcoming. (The full text of the questions and responses can be found here.)

On Feb. 15, the California Stem Cell Report followed up with these additional questions,

"Regarding the 300 stakeholder groups, how are those defined? Please give me a few examples.

"Based on your response, is it correct to say that the IOM is not sending out questionnaires directly to all CIRM grant applicants, including those who were rejected?

"Is it correct to say that no special effort -- other than that described in your response -- is being made to seek responses from stem cell businesses?

"The failure to provide numbers on the responses so far would indicate that the numbers are so small that the IOM is choosing not to disclose them. If that is not the case, please email me the numbers."

As of this writing, the IOM has not responded to those questions. We will carry its response verbatim when we receive it.

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

Here is the text of the questions submitted Feb. 12 by the California Stem Cell Report to the Institute of Medicine concerning its attempts to secure comments on the operation of the $3 billion California stem cell agency along with the IOM response.

The response from Christine Stencel, a spokeswoman for the IOM, follows these questions from the California Stem Cell Report.

"I will be writing a piece on Wednesday dealing with the online surveys that IOM has posted. For that piece, please tell me very, very  specifically what the IOM is doing to generate responses. For example, is the IOM buying ads in newspapers or online, asking the public to fill out the forms? Is it hiring a polling firm to call households for responses?  Also please tell me exactly what is being done to generate responses on all the other surveys that have been posted.

"Additionally, please tell me how many responses that the IOM has received so far in each category on the survey forms for CIRM grantees, industry partners and leadership. Thank you."

The IOM response on Feb. 15:

"The IOM has been obtaining and compiling lists of organizations and people to circulate the questionnaires as widely as possible among target groups. For example, IOM has sent a notice to some 300 stakeholder groups encouraging participation. We do not have the resources to hire a polling firm or place ads.

"The purpose of these questionnaires is to extend the committee's information gathering beyond in-person meetings and the standard listing of an email address or phone number for the study on the project website. Not all people who might have useful experiences or perspectives on CIRM may be able to attend the in-person meetings and not all may visit the project website and find the study contact information. This is a proactive effort to reach more people.

"Anyone who knows of individuals or organizations with information on CIRM that would be useful for the committee's knowledge can share the links to the questionnaires with them. This will help spread the word and get the committee insights they need.

"I don't have information on the number of responses so far. Ultimately, as noted at the top of each survey, the responses will be aggregated and de-identified and placed in the public access file in addition to being shared with the committee.

"I trust this will be useful for your readers."

The California Stem Cell Report then asked the following questions on Feb. 15.

"Thank you for your response. A few follow-up questions:
Regarding the 300 stakeholder groups, how are those defined? Please give me a few examples.

"Based on your response, is it correct to say that the IOM is not sending out questionnaires directly to all CIRM grant applicants, including those who were rejected?

"Is it correct to say that no special effort -- other than that described in your response -- is being made to seek responses from stem cell businesses?

"The failure to provide numbers on the responses so far would indicate that the numbers are so small that the IOM is choosing not to disclose them. If that is not the case, please email me the numbers. Thank you."

The IOM had not responded to the follow-up questions as of this writing on Feb. 21.

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

by: John Phillip

Researchers publishing in the Canadian Journal of Physiology and Pharmacology (CJPP) have found that a diet enhanced with vitamin and mineral supplementation can lower the risk of developing precancerous colon cancer lesions by up to 84%. Colon cancer is the second most common form of the disease affecting men and women in the US, with nearly 150,000 new diagnoses each year.

Nutrition experts and alternative practitioners understand that cancer is largely a disease caused by poor lifestyle behaviors including a diet lacking an optimal intake of vitamins and minerals. Chronic illnesses including colon cancer are the result of many years and decades of low nutritional status, as support for a healthy immune response is suppressed. Scientists now provide compelling evidence in support of whole-food based vitamin and mineral supplementation to dramatically lower the risk of colorectal cancer. Read more...

AyurGold for Healthy Blood

Source:
http://feeds.feedburner.com/integratedmedicine