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

Excerpt from:
Ovarian Stem Cells Produce Eggs in Method That May Aid Fertility

An experiment that produced human eggs from stem cells could one day be a boon for women who are desperate to have a baby, according to a study published on Sunday.

The work sweeps away the belief that a woman has only a limited stock of eggs and replaces it with the theory that the supply is continuously replenished from precursor cells in the ovary, its authors said.

"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," said 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 that they had only been conducted on lab mice.

But the new work, said Tilly, not only confirms his controversial idea, but takes it farther.

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 work needs to be done to test the viability of the eggs, and little is known about the hormones or other mechanisms by which oocytes emerge from the stem cells.

But the impact could be far-reaching, Tilly said.

"If we can guide the process correctly, I think it opens up a chance that sometime in the future, we might get to the point of actually having an unlimited source of human eggs," Tilly said in a video recording released to the press.

"A woman could come in, have a small biopsy taken from her ovary for us to retrieve these cells. Once we get these cells out, we can take a hundred of them and make a million of them.

"If we can get to the stage of generating functional human eggs outside the body, it would rewrite essentially human assisted reproduction."

According to a press release issued by Massachusetts General Hospital, Tilly's team are already exploring the idea of banks where oocyte stem cells can be frozen and stored, and then retrieved when a woman wants to have a baby.

Human eggs are extremely delicate and likely to suffer damage when frozen and thawed, but this risk does not apply to the egg cells that make them, it said.

Previous work has shown that around one in 10 women of reproductive age is at risk of premature ageing of the ovaries, a finding with repercussions in societies where women opt ever later to become mothers.

Continued here:
Pioneering lab work aims to smash women's fertility barrier

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.

Read more:
Report: Stem cells may create new eggs

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.

Read more from the original source:
Ovary stem cells can produce new eggs, researchers say

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