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

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

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

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

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

His theory ran into a firestorm.

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

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

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

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

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

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

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

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

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

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Human eggs produced from stem cells

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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The above story is reprinted from materials provided by Massachusetts General Hospital.

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Journal Reference:

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

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

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

See the article here:
Egg-producing stem cells isolated from adult human ovaries

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

PICTURES: Human eggs: 9 fascinating facts

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

What happened? New egg cells formed within two weeks.

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

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

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

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

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

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

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

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

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

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

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

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

M I Walker / Getty Images

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Egg quality questions

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

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

Researchers watched through a microscope as new eggs grew in a lab dish. Then came the pivotal experiment: They injected the stem cells into pieces of human ovary. They transplanted the human tissue under the skin of mice, to provide it a nourishing blood supply.

Within two weeks, they reported telltale green-tinged egg cells forming.

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

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

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

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

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

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

Continue reading here:
Egg-producing stem cells found in women's ovaries

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

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

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

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

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

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

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

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

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

Mr. Tilly collaborated with scientists at Japan’s Saitama Medical University who were freezing ovaries donated for research by healthy 20-somethings who underwent a sex-change operation.

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

“Bang, it worked - cells popped right out” of the human tissue, Mr. Tilly said.

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

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

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

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

Excerpt from:
Report says women have egg-producing stem cells

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.

Read more:
Rare stem cells may produce new eggs, scientists say

In research that could have far-reaching implications for female fertility, U.S. scientists have isolated stem cells from human ovarian tissue that give rise to what appear to be normal egg cells.

The finding, published Sunday in the journal Nature Medicine, builds on earlier landmark papers by the Boston researchers, which suggest that female mammals continue producing egg cells, known as oocytes, into adulthood.

Since 2004, the scientists at Massachusetts General Hospital have produced a series of papers based on work in laboratory mice, which challenge the long-held belief that female mammals are born with a finite number of eggs that run out at a certain point in the life cycle.

The team was able to isolate stem cells from ovarian tissue taken from mice, from which they grew fully functional egg cells in the lab, which could then be fertilized and even produce healthy offspring.

"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," said lead author Jonathan Tilly, director of the Vincent Center for Reproductive Biology at Massachusetts General.

In their experiments, the team isolated the stem cells from ovarian tissue that had been removed from women in their 20s and early 30s.

When put in culture dishes in the lab, these stem cells gave rise to cells with the characteristic features of oocytes, including the physical appearance and gene expression patterns of those seen inside human ovaries.

"They spontaneously generate eggs in the dish," Tilly said in a phone interview, noting that they proliferate so well that a small number of stem cells could easily spawn a million egg cells in the lab.

The researchers next took stem cells they had genetically manipulated to glow green and injected them into snippets of human ovarian tissue. These prepared tissue bits were then grafted beneath the skin of specially bred mice, which have no immune system that can cause rejection of human tissue.

Within two weeks, researchers discovered the implanted ovarian tissue in the mice contained numerous immature human follicles with egg cells that originated from the injected stem cells. Follicles are small sacs within the ovary which contain maturing eggs.

Tilly said they knew the eggs cells had arisen from the injected stem cells "because they were all green."

Among the many potential clinical applications the researchers are exploring is whether these stem cells could produce oocytes that could play a role in in-vitro fertilization, as well as other applications to improve the outcomes of IVF and other infertility treatments.

"Can we use these cells for fertility reasons to maximize the opportunity for patients who are experiencing infertility to have different options available to them to have a genetically matched child?" asked Tilly.

"I think it's a fairly good possibility that at some point in the not-too-distant future there will be clinical protocols developed using some aspect of these cells or their properties that will have a significant impact on human reproduction."

Among them is the idea of extracting structures responsible for energy production in cells — called mitochondria — from the stem cells and injecting them into a woman's eggs at the time of in-vitro fertilization, with the hope of boosting the chances of conception and a successful birth.

But Tilly said another idea is to see whether these ovarian stem cells could be used to delay menopause — and the myriad health effects that can develop as women age.

"I've always been intrigued by the prospects of what if you could slow the rate at which the egg cell pool goes away and end up keeping an ovary functioning long past its normal time of failure," he said.

"With these egg stem cells, it raises the prospect that by harnessing the power of those cells, perhaps we can control the rate at which that precious reserve of egg cells is depleted and maybe even delay it ... And if you could achieve that, what would happen? Would we truly see a benefit or would there be unforeseen bad effects?"

More than a decade ago, Tilly's lab created a mouse through genetic manipulation that did not experience ovarian failure with age and was able to maintain an adequate reservoir of eggs.

"So it didn't undergo the equivalent of menopause," he said, or "mouseopause" as the scientists have dubbed it.

While normal mice as they reach old age experience health problems similar to those of postmenopausal women — including declining eyesight and hearing, hair loss, osteoporosis, diminished cognitive function and reduced muscle mass — these genetically modified mice did not. Nor did they have an increased risk of cancer.

So could these stem cells one day be used as the basis for an anti-aging treatment?

"There would be some pretty significant health benefits that would come out of it," said Tilly, if that were the case.

Even though every aspect of the human oocyte-producing stem cells have so far matched what the researchers have found in their mouse equivalents, Tilly conceded that "mouse is mouse — and perhaps human will be different."

"We don't know" if eggs generated from human ovarian stem cells will be normal and healthy, he said. "We will have to be very careful if and when we get to that stage."

Go here to read the rest:
Human ovarian stem cells may hold promise for treating infertility: study

Researchers have found that it is possible for stem cells in adult women to produce human eggs in the laboratory, according to the BBC.

The study, published in the journal Nature Medicine, said further experiments on mice showed that eggs derived in such a manner can be fertilized, potentially opening the door for creating an unlimited supply of eggs in order to treat infertility.

Bloomberg reported that the research was conducted by a team led by Jonathan Tilly, the director of Massachusetts General Hospital’s Vincent Center for Reproductive Biology, which is affiliated with Harvard University.

The research builds on a discovery in 2004, in which Tilly found that ovarian stem cells in mice could create new eggs, said Bloomberg. The study’s findings challenge the belief that a woman’s ovaries can’t make any more eggs after menopause.

More on GlobalPost: Stem cells used to heal heart attack damage

The New York Times said the research used a cell-sorting machine to target a special protein that marks the surface of reproductive cells. Using those cells, the team was able to generate eggs that could potentially be fertilized and then produce embryos.

Dr. Tilly said, "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."

More on GlobalPost: Scientists create brain cells from human skin in possible breakthrough for autism, Alzheimer's research

Below is the video from Nature Medicine explaining more about the procedure:

http://www.globalpost.com/dispatch/news/health/120226/researchers-used-stem-cells-produce-human-eggs

Originally posted here:
Researchers used stem cells to produce human eggs

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Read this article:
Report: Women have rare egg-producing stem cells

By The Associated Press

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

More here:
Report: Stem cells may create new eggs

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

See the article here:
Ovarian Stem Cells Produce Eggs in Method That May Aid Fertility

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

See the rest here:
Ovary stem cells can produce new eggs, researchers say

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

See the original post here:
Ovarian Stem Cells Make Human Eggs in Possible Aid to Fertility

By Ryan Flinn - Mon Feb 27 05:00:01 GMT 2012

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.

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

Read this article:
Ovarian Stem Cells Produce Eggs in Method That May Aid Fertility Therapy

Breakthrough stem cell research at Scripps Research Institute in La Jolla, Calif. has the potential to revive endangered species. Researchers at the Center for Regenerative Medicine are aiming to turn stem cells into gametes. Once new eggs and sperm are created, “test tube babies” can be born, possibly preserving a species.

In 1972, researchers preserved skin cells of certain endangered species at the Frozen Zoo, hoping that future technology would help to revive populations, and today Scripps researchers are combining the frozen skin cells with human stem cells to generate stem cells specific to the animal. Stem cells are turned into gametes through re-programming, a process in which retroviruses are used to bring the cells back to earlier stages of development. Last month, scientists created mouse sperm cells through this process.

Scientists view this method of species preservation as a last resort when cheaper, simpler means have failed. For instance, the white rhino, whose population is numbered at seven in the world, would benefit immensely since other methods of trying to save the species have failed. Scientists also hope to help the drill, a West African primate threatened by hunting and habitat degradation.

—compiled by Michelle Lim

Go here to read the rest:
One Response to “Rescuing the white rhino?”

An important new study by a team of scientists at RhinoCyte™ Inc., Louisville, Ky., details promising results on the effectiveness of olfactory (nasal) stem cells in repairing spinal cord damage resulting from the most common cause of these injuries — contusions (bruising) due to major trauma such as is seen in auto accidents, falls or combat. This could have major implication for the estimated 5 million people worldwide affected by spinal cord injuries – 1.275 million of them in the United States alone, where the cost of treatment exceeds $40.5 billion each year.

Louisville, Kentucky (PRWEB) February 22, 2012

An important new study released by a team of scientists at RhinoCyte™ Inc., Louisville, Ky., details promising results on the effectiveness of olfactory (nasal) stem cells in repairing spinal cord damage resulting from the most common cause of these injuries — contusions (bruising) due to major trauma. Their study is featured in the current issue of the Journal of Neurodegeneration and Regeneration.

The study, led by Dr. Fred Roisen, has great implication for the estimated 5 million people worldwide affected by spinal cord injuries – 1.275 million of them in the United States alone, where the cost of treatment exceeds $40.5 billion each year. Current treatment options are limited to retaining and retraining mobility; no drug therapies are available, but studies pertaining to stem cell treatments are showing great promise for these as well as other neurodegenerative conditions.

A previous study by the group made national headlines when lab rats whose spinal cords had been partially cut in the region of the animal’s neck in a way that disabled their front right paws were able to regain significant use of their paws after being injected with olfactory stem cells. The investigative team took the cells from the olfactory neurosensory epithelium — the part of the nose that controls the sense of smell — in adult volunteer donors who were already undergoing elective sinus surgery. The removal of the stem cells has no effect on the patients’ ability to smell. Also, the minimally invasive surgery is frequently done on an outpatient basis so the cells are readily available and, as such, are a potentially promising source of therapeutic stem cells.

The researchers isolated the stem cells and increased their numbers in the laboratory by growing them in an enriched solution. The cells were then injected into a group of lab rats. Twelve weeks later, these animals had regained control of their affected paws while a control group that received no cells had not.

This latest study continued that original work, by concentrating on contusions caused by blunt force trauma such as that resulting from an automobile accident or a fall. Spinal cord and head trauma are common among soldiers suffering serious combat injuries, too.

Two independent sets of experiments were conducted, beginning two weeks after the rats had received contusions administered in a computer-controlled surgery. In the first group, 27 out of 41 rats were injected with olfactory stem cells, while the remainder received none. In the second group, 16 rats were treated with olfactory stem cells, 11 received no treatment and 10 received stem cells grown from human skin to see how the olfactory cells compared with another stem cell source.

The results once again showed great promise, with 40 percent of the rats treated with the olfactory-derived stem cells showing significant improvement after just six weeks, compared to 30 percent of those treated with human skin-derived cells and only 9 percent of those receiving no treatment. In addition, the olfactory stem cell-treated rats showing the highest rate of improvement recovered much faster than the other groups.

“This is very exciting on numerous levels,” said Dr. Roisen. “As an autologous cell source — that is, the patient is both the donor and the recipient — olfactory stem cells bypass the time a patient must wait while a suitable donor is found, which can be critical to the outcome of the patient’s treatment. They also eliminate the need for immunosuppressive drugs, which have numerous negative side effects.

“And just as importantly, stem cells taken from the nose of an adult do away with the ethical concerns associated with using embryonic stem cells.”

The researchers are in the final stages of their enabling studies, which are scheduled to be completed by summer; Phase 1 safety studies could begin as soon as early next year.

Dr. Roisen is chief science officer and co-founder of RhinoCtye™, and a professor and chair of the University of Louisville School of Medicine’s Department of Anatomical Sciences and Neurobiology. The original work forming the basis for the contusion study was conducted by Dr. Roisen’s group at UofL and has been licensed to RhinoCtye™ (http://www.rhinocyte.com), a company he co-founded in 2005 with Dr. Chengliang Lu and Dr. Kathleen Klueber to develop and commercialize diagnostic tools and therapies for stem cell treatment of multiple degenerative and traumatic neurological diseases. RhinoCyte™ currently has three patents for olfactory stem cell treatments approved in the United States, Australia and Israel, with others pending worldwide.

###

Laurel Harper
Laurel92@msn.com
502-550-0089
Email Information

Read more:
Nasal Stem Cells Show Promise in Repairing Spinal Cord Damage Caused by Contusion

Monkeys suffering from Parkinson's disease show a marked improvement when human embryonic stem cells are implanted in their brains, in what a Japanese researcher said Wednesday was a world first.

A team of scientists transplanted the stem cells into four primates that were suffering from the debilitating disease.

The monkeys all had violent shaking in their limbs -- a classic symptom of Parkinson's disease -- and were unable to control their bodies, but began to show improvements in their motor control after about three months, Kyoto University associate professor Jun Takahashi told AFP.

About six months after the transplant, the creatures were able to walk around their cages, he said.

"Clear improvements were confirmed in their movement," he said.

Parkinson's disease is a progressive neurological illness linked to a decrease in dopamine production in the brain. There is currently no medical solution to this drop off in a key neurotransmitter.

The condition, which generally affects older people, gained wider public recognition when Hollywood actor Michael J. Fox revealed he was a sufferer.

Takahashi said at the time of the implant about 35 percent of the stem cells had already grown into dopamine neuron cells, with around 10 percent still alive after a year.

He said he wants to improve the effectiveness of the treatment by increasing the survival rate of dopamine neuron cells to 70 percent.

"The challenge before applying it to a clinical study is to raise the number of dopamine neuron cells and to prevent the development of tumours," he said.

"I would like to make this operation more effective and safe" before clinical trials, Takahashi said.

Takahashi said so far he had used embryonic stem cells, which are harvested from foetuses, but would likely switch to so-called Induced Pluripotent Stem (iPS) cells, which are created from human skin, for the clinical trial.

His team, which has also transplanted iPS cells into monkeys, are now looking to see if the primates with Parkinson's disease show similar improvements in their motor control.

Scientists say the use of human embryonic stem cells as a treatment for cancer and other diseases holds great promise, but the process has drawn fire from religious conservatives, among others.

Opponents say harvesting the cells, which have the potential to become any cell in the human body, is unethical because it involves the destruction of an embryo.

The Japanese government currently has no guidelines on the use of human stem cells in clinical research.

In October last year, the Court of Justice of the European Union banned the patenting of stem cells when their extraction causes the destruction of a human embryo, a ruling that could have repercussions on medical research.

Scientists warned that the ruling would damage stem cell research in Europe, while the Catholic church hailed it as a victory for the protection of human life.

See more here:
Stem cell implants boost monkeys with Parkinson's

SCOTTSDALE, Ariz., Feb. 21, 2012 /PRNewswire-USNewswire/ -- Makucell, Inc., a new life science company that utilizes an innovative proprietary regenerative medicine technology to address aging skin, hair and nail conditions, has presented important pre-clinical and clinical information on its proprietary molecule, Asymmtate, at the 36th Annual Hawaii Dermatology Seminar, Waikoloa, Hawaii.  Asymmtate™ is the active key ingredient in Makucell's new topical skin care line Renewnt™ (pronounced "Re-new-int").

Asymmtate™ is a selective modulator of the Wnt (pronounced "wint") signaling pathway that encourages optimal signaling to stimulate skin stem cells to replenish themselves, keratinocytes, fibroblasts and other dermal cells, which produce collagen, elastic tissue, matrix and other substances to foster a more healthy, rejuvenated appearing skin.  Renewnt™ will be available through aesthetic dermatology professionals in April 2012.

Mark Dahl, M.D. Makucell's, Vice President and Chief Medical Officer, presented the two scientific poster presentations.   The presentation titles and conclusions are summarized below.

The Safety and Efficacy of Asymmtate – Asymmtate™ penetrates into human epidermis and dermis and remains active.  Asymmtate in its cream vehicles is non-mutagenic, non-irritating, and non-sensitizing.  Asymmtate™ Analog Mitigates Photoaging Effects of UVB in Mice – An analog of Asymmtate applied topically can mitigate the subsequent visible appearance of photoaging changes in mice after exposures of their skin to UVB.

In addition to the pre-clinical/clinical information presented this week, Makucell has initiated a 100 subject Use Study to evaluate the safety and efficacy of Renewnt™ for Hydration Day and Night Moisturizer in a real world setting.  This four-week study will include 12 investigator sites across the U.S.  "This large multicenter study is very important to validate aspects of clinical product performance of Asymmtate™ under real world conditions.  The diverse geographical study sites will allow us to evaluate effects on unique skin types in different climates," said Lawrence A. Rheins, President and CEO of Makucell.

The innovative technology that resulted in the formulation of Renewnt was developed by distinguished research scientist Michael Kahn, Ph.D. and colleagues at the Eli & Edythe Broad Center for Stem Cell and Regenerative Medicine at the University of Southern California, Keck School of Medicine. "This is an exciting time for Makucell," said Makucell co-founder and inventor Michael Kahn, Ph.D.  "This technology will be utilized for commercial topical applications to address the challenges of photoaging skin and other hair and nail conditions."

For media and investment inquiries please contact please contact Lawrence Rheins, lrheins@makucellinc.com or 1-855-MAKUCELL.

About Makucell
Makucell (www.makucell.com) is a new life science technology transfer company that utilizes an innovative proprietary regenerative medicine technology to address aging skin, hair and nail conditions in an entirely new way. Using a patent-pending new molecule, Asymmtate, Makucell has developed the Renewnt brand of non-prescription products that work with the skin's own stem cells to produce healthier, and more youthful appearing skin. This innovative technology was developed by researchers at the Eli & Edythe Broad Center for Stem Cell and Regenerative Medicine at the University of Southern California Keck School of Medicine.  Makucell is financed through private investors and is not in receipt of government funding.

About the USC Stevens Institute for Innovation
The USC Stevens Institute for Innovation (http://stevens.usc.edu) is a university-wide resource in the Office of the Provost at the University of Southern California that helps identify, nurture, protect, and transfer to the market the most exciting innovations from USC.  It also provides a central connection for industry seeking cutting-edge innovations in which to invest. As part of this role, the USC Stevens Institute manages the university's intellectual property portfolio stemming from its $560M annual research program. Furthermore, the USC Stevens Institute develops the innovator as well as innovations, through educational programs, community-building events, and showcase opportunities.

Media Contact:
Lawrence Rheins
lrheins@makucellinc.com
1-480-305-2061

SOURCE USC Stevens Institute for Innovation

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RELATED LINKS
http://www.stevens.usc.edu
http://www.makucell.com/

Original post:
Makucell™ Announces Key Scientific Presentations and Launch of a Large, Multicenter Use Study of Asymmtate™

To: HEALTH, MEDICAL AND NATIONAL EDITORS

SCOTTSDALE, Ariz., Feb. 21, 2012 /PRNewswire-USNewswire/ -- Makucell, Inc., a new life science company that utilizes an innovative proprietary regenerative medicine technology to address aging skin, hair and nail conditions, has presented important pre-clinical and clinical information on its proprietary molecule, Asymmtate, at the 36th Annual Hawaii Dermatology Seminar, Waikoloa, Hawaii. Asymmtate(TM) is the active key ingredient in Makucell's new topical skin care line Renewnt(TM) (pronounced "Re-new-int").

Asymmtate(TM) is a selective modulator of the Wnt (pronounced "wint") signaling pathway that encourages optimal signaling to stimulate skin stem cells to replenish themselves, keratinocytes, fibroblasts and other dermal cells, which produce collagen, elastic tissue, matrix and other substances to foster a more healthy, rejuvenated appearing skin. Renewnt(TM) will be available through aesthetic dermatology professionals in April 2012.

Mark Dahl, M.D. Makucell's, Vice President and Chief Medical Officer, presented the two scientific poster presentations. The presentation titles and conclusions are summarized below.

-- The Safety and Efficacy of Asymmtate - Asymmtate(TM) penetrates into human epidermis and dermis and remains active. Asymmtate in its cream vehicles is non-mutagenic, non-irritating, and non-sensitizing. -- Asymmtate(TM) Analog Mitigates Photoaging Effects of UVB in Mice - An analog of Asymmtate applied topically can mitigate the subsequent visible appearance of photoaging changes in mice after exposures of their skin to UVB.

In addition to the pre-clinical/clinical information presented this week, Makucell has initiated a 100 subject Use Study to evaluate the safety and efficacy of Renewnt(TM) for Hydration Day and Night Moisturizer in a real world setting. This four-week study will include 12 investigator sites across the U.S. "This large multicenter study is very important to validate aspects of clinical product performance of Asymmtate(TM) under real world conditions. The diverse geographical study sites will allow us to evaluate effects on unique skin types in different climates," said Lawrence A. Rheins, President and CEO of Makucell.

The innovative technology that resulted in the formulation of Renewnt was developed by distinguished research scientist Michael Kahn, Ph.D. and colleagues at the Eli & Edythe Broad Center for Stem Cell and Regenerative Medicine at the University of Southern California, Keck School of Medicine. "This is an exciting time for Makucell," said Makucell co-founder and inventor Michael Kahn, Ph.D. "This technology will be utilized for commercial topical applications to address the challenges of photoaging skin and other hair and nail conditions."

For media and investment inquiries please contact please contact Lawrence Rheins, lrheins@makucellinc.com or 1-855-MAKUCELL.

About Makucell

Makucell (www.makucell.com) is a new life science technology transfer company that utilizes an innovative proprietary regenerative medicine technology to address aging skin, hair and nail conditions in an entirely new way. Using a patent-pending new molecule, Asymmtate, Makucell has developed the Renewnt brand of non-prescription products that work with the skin's own stem cells to produce healthier, and more youthful appearing skin. This innovative technology was developed by researchers at the Eli & Edythe Broad Center for Stem Cell and Regenerative Medicine at the University of Southern California Keck School of Medicine. Makucell is financed through private investors and is not in receipt of government funding.

About the USC Stevens Institute for Innovation

The USC Stevens Institute for Innovation (http://stevens.usc.edu) is a university-wide resource in the Office of the Provost at the University of Southern California that helps identify, nurture, protect, and transfer to the market the most exciting innovations from USC. It also provides a central connection for industry seeking cutting-edge innovations in which to invest. As part of this role, the USC Stevens Institute manages the university's intellectual property portfolio stemming from its $560M annual research program. Furthermore, the USC Stevens Institute develops the innovator as well as innovations, through educational programs, community-building events, and showcase opportunities.

Media Contact:

Lawrence Rheinslrheins@makucellinc.com1-480-305-2061

SOURCE USC Stevens Institute for Innovation

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Makucell(TM) Announces Key Scientific Presentations and Launch of a Large, Multicenter Use Study of Asymmtate(TM)