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Archive for February, 2012

Penn State Launches Personalized Medicine Institute

By Matt Jones

NEW YORK (GenomeWeb News) – The Penn State Milton S. Hershey Medical Center and the Penn State College of Medicine have launched a new institute that will focus on personalized medicine and engage in interdisciplinary research with other institutes at the campus.

The Penn State Hershey Institute for Personalized Medicine will connect faculty, resources, and programs currently at the school to advance research areas that could translate into clinical applications, Penn State Hershey said late last week.

The institute will collaborate with departments and institutes around the Penn State Hershey campus, including the Penn State Clinical and Translational Science Institute, to translate research findings into clinical applications.

The institute, which will move into its permanent lab space in the College of Medicine in June, will obtain blood and other biosamples from consenting patients at the Medical Center which will then be stored in a biorepository, also housed on campus.

Along with the samples, information about the patients' treatments and outcomes stored on electronic medical records will be deposited in a database for use in correlation studies, James Broach, who chairs the department of biochemistry and molecular biology at Penn State College of Medicine and who will be the inaugural director of the institute, told GenomeWeb Daily News on Monday.

"This has the potential to expand to the nearly a million people who come through the hospital and the associated clinics under the umbrella of the Hershey Medical Center," he said.

Depending on the disease interest, the samples can be pulled from the repository and analyzed in any number of ways, including conducting SNP analyses using Illumina's SNP arrays, and in-house deep sequencing studies with the Illumina HiSeq and other next-generation sequencing platforms, Broach said.

The large volumes of data the institute expects to generate will be analyzed by researchers at Penn State's University Park campus using the Galaxy software package to identify relevant SNPs for each individual patient. Developed by Penn State and Emory University, Galaxy is an open source system for data integration and analysis that was developed for genomics research and now is used as a general bioinformatics workflow management system.

The institute will then seek to compare the genomic information with the outcome and treatment data found in the EMRs.

Establishing correlations between genotype and outcomes is the hard part, Broach explained, because of the large number of patients that are required to identify parts of the genome that are correlated to diseases with any statistical significance.

"Our approach will be much in the way that people are beginning to think about doing clinical trials with limited a number of patients – where you keep redirecting the cohort as the information comes in," Broach said.

The early phases of research will focus on this type of study, with the longer aim of generating knowledge linking genes and variants with outcomes in ways that could be used in treatment.

"Ultimately, the goal will be that when the patient comes in, we take their blood samples, we do the sequence, we get the SNPs, and on the basis of our previous correlations, you can make the prediction that this person would respond to one treatment versus another treatment," he said.

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Penn State Launches Personalized Medicine Institute

Kalorama: "Personalized Medicine" May Not Be New, but It Is Growing

NEW YORK, NY--(Marketwire -02/27/12)- Personalized medicine, or matching an individual patient to an individual treatment, has long been part of diagnostic testing, according to healthcare market research publisher Kalorama Information. But Kalorama estimates that new proven biomarkers, and a desire to better target cancer therapy, have grown personalized medicine testing to a $28 billion market in 2011. This finding was made in Kalorama's latest report: World Market for Personalized Medicine Diagnostics.

"The excitement over personalized medicine is reminiscent of the dot-com era, but the concept is not completely new," says Kalorama's lead diagnostic analyst Shara Rosen. She notes in the report that matching a drug's effectiveness with a patient's genetics has been considered since the 1950s. Blood testing, transplant tissue testing, microbial identification and AST susceptibility are examples of individualized testing that Rosen notes have been part of medicine for decades and these are considered in the report's analysis.

However, the study acknowledges that the current excitement in IVD, and a share of the growth in this market, is coming from new molecular tests and the profiling of solid cancer tumors, which the report says are creating an entirely new paradigm for diagnosing and choosing treatment options. These new tests are driving the market to better-than-average growth rates compared to other segments of the IVD market. Kalorama sees the primary growth drivers in the market are the discovery of biomarkers with clinical utility and better reimbursement for testing. But as the author of the report notes, the missing piece that is making the concept a reality is recent technology improvements.

"Cost-effective multiplex platforms, high powered software, assays using saliva, urine, and blood instead of biopsied tissue, these are the technological tools that make more sensitive and specific tests possible," says Rosen.

Kalorama also notes in the report that healthcare delivery trends and novel therapeutics help refocus the role of laboratory medicine in disease management to the patient by helping individualize diagnoses and treatments. Decentralization and wider availability of PMx (personalized medicine) tests can only happen with the conversion of lab-developed tests (LDTs) to CE Marked and FDA-cleared molecular testing methods. Advances in cancer therapies and the allure of personalized medicine provide another compelling argument for growth in the routine use of these tests.

In the full study, World Market for Personalized Medicine Diagnostics, Kalorama Information defines the current opportunity and realistic future potential of personalized medicine in clinical testing. In addition to analysis of tests currently on the market and in development, the report profiles key competitors and discusses trends that are important for understanding this much-discussed growth area of the diagnostic industry. It also profiles scores of companies that are involved in making tests for this market.

About Kalorama Information
Kalorama Information, a division of MarketResearch.com, supplies the latest in independent medical market research in diagnostics, biotech, pharmaceuticals, medical devices and healthcare; as well as a full range of custom research services. We routinely assist the media with healthcare topics. Follow us on Twitter, LinkedIn and our blog.

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Kalorama: "Personalized Medicine" May Not Be New, but It Is Growing

Olympian Mary Alison Milford is a True to Herself Athlete

When she was just three years old, Mary Alison Milford suffered a spinal cord injury that left her paralyzed from the waist down. A year later, with her frail physique still too small for the wheelchairs made for basketball, Mary began playing anyway. Milford watched the Olympic Games throughout her elementary and high school years, fantasizing about what it would be like to be a Paralympic athlete.

By the time she was 10; Mary had begun competing in wheelchair basketball at her elementary school, and had already set her goal of playing on the American Paralympic Team. In March of 2007 at age 19, Milford moved one-step closer to accomplishing that goal by helping to win the silver medal at the 2006 wheelchair Basketball World Championships, earning her the right to try out for the American Paralympic team. In 2007, she made the final cut along with three of her teammates.

That was just the beginning for the dedicated athlete. The following year she helped win gold in two separate world events, one in Rio de Janeiro, Brazil, and the other in Birmingham, Alabama. That same year her dream of playing in the Paralympics was realized during the 2008 Beijing Games; and America won gold for the third time that year. In 2010 and 2011, the champion kept the streak going, helping the team win gold in two more championship events.

2012 finds the 26-year-old star preparing for the upcoming London extravaganza. Now a seasoned pro and considered one of the best in her sport, Milford is excited about the upcoming competition. The American Team will be attempting to reign as the best in the world at the Paralympic Games for the third time in a row.

Mary displays the quintessential aspects of a true team player. More concerned about the team than her own stats, Milford focuses on defense and makes sure other players are free to shoot and score. Her unselfish habits on the court have made her one of the most appreciated members of the team.

Holding a degree from the University of Alabama in Spanish and public relations, Mary holds the keys to a bright future long after her basketball career has ended. Until that time arrives, we Americans are fortunate to have her on our side of the basketball court, and wish her success in London.

Note: This article was written by a Yahoo! contributor. Sign up here to start publishing your own sports content.

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Olympian Mary Alison Milford is a True to Herself Athlete

Harvard Bioscience, Inc. Schedules Fourth Quarter 2011 Conference Call for March 1, 2012

HOLLISTON, Mass., Feb. 27, 2012 (GLOBE NEWSWIRE) -- Harvard Bioscience, Inc. (Nasdaq:HBIO - News), a global developer, manufacturer and marketer of a broad range of specialized products used to advance life science research and regenerative medicine, will announce results for its fourth quarter and year ended December 31, 2011 before market trading hours on Thursday, March 1, 2012.

A conference call to discuss the company's fourth quarter and year ended December 31, 2011 financial results is scheduled for Thursday, March 1, 2012 at 11:00 a.m. Boston time. In addition, management may answer questions concerning business and financial developments and trends, the Company's view on earnings forecasts, update on its regenerative medicine device business, and other business and financial matters affecting the Company. Some of the information to be presented on the call or provided in response to questions may contain information that has not previously been disclosed.

The conference call will be simultaneously broadcast over the Internet and can be accessed through the Harvard Bioscience, Inc. website. To listen to the conference call, log on to our website at http://www.harvardbioscience.com and click on the Earnings Call icon. Financial and other statistical information presented on the call, including our earnings release, will also be available on the investor relations section of our website. Click on the investor relations button and then click on the press release or webcast icon, as appropriate. If you are unable to listen to the live webcast, the call will be archived in the investor relations section of our website. The live conference call is also accessible by dialing toll-free 877-303-7611, or toll 970-315-0445, and referencing the pass code of "50805769".

Date: March 1, 2012
Time: 11:00 AM ET

Listen via Internet: http://www.harvardbioscience.com/

Schedule this webcast into MS-Outlook calendar (click open when prompted): http://apps.shareholder.com/PNWOutlook/t.aspx?m=51987&k=66A501E5

A replay of this conference call will be available from approximately 2:00 p.m. on March 1, 2012 through March 10, 2012 and will be accessible by dialing toll-free 855-859-2056, or toll 404-537-3406, and referencing the pass code of "50805769".

About Harvard Bioscience

Harvard Bioscience ("HBIO") is a global developer, manufacturer and marketer of a broad range of specialized products, primarily apparatus and scientific instruments, used to advance life science research and regenerative medicine. HBIO sells its products to thousands of researchers in over 100 countries primarily through its 850 page catalog (and various other specialty catalogs), its website, through distributors, including GE Healthcare, Thermo Fisher Scientific and VWR, and via our field sales organization. HBIO has sales and manufacturing operations in the United States, the United Kingdom, Sweden, Germany and Spain with additional facilities in France and Canada.

For more information, please visit http://www.harvardbioscience.com.

The Harvard Bioscience, Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=8160

The statements made in this press release that are not statements of historical fact are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These statements involve known and unknown risks, uncertainties and other factors that may cause the Company's actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Factors that may cause the Company's actual results, performance or achievements to differ materially from those in the forward-looking statements include, but are not limited to, those factors set forth under the heading "Item 1A. Risk Factors" in the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2010 or described in the Company's other public filings. The Company's results may also be affected by factors of which the Company is not currently aware. The Company may not update these forward-looking statements, even though its situation may change in the future, unless it has obligations under the federal securities laws to update and disclose material developments related to previously disclosed information.

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Harvard Bioscience, Inc. Schedules Fourth Quarter 2011 Conference Call for March 1, 2012

Bad breath used as stem cell tool

27 February 2012 Last updated at 00:06 ET

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

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

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

Small amounts of hydrogen sulphide are made by the body.

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

Therapy

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

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

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

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

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

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

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

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Bad breath used as stem cell tool

'Bad breath' chemical may fuel development of dental pulp stem cells

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

In the study, Japanese scientists showed that hydrogen sulphide (H2S) increased the ability of adult stem cells to differentiate into hepatic (liver) cells, furthering their reputation as a reliable source for future liver-cell therapy.

This is the first time that liver cells have been produced from human dental pulp and, even more impressively, have been produced in high numbers of high purity.

"High purity means there are less 'wrong cells' that are being differentiated to other tissues, or remaining as stem cells. Moreover, these facts suggest that patients undergoing transplantation with the hepatic cells may have almost no possibility of developing teratomas or cancers, as can be the case when using bone marrow stem cells," said lead author of the study Dr. Ken Yaegaki.

The remarkable transforming ability of stem cells has led to significant focus from research groups around the world and given rise to expectations of cures for numerable diseases, including Parkinson's and Alzheimer's.

In this study, Dr. Yaegaki and his group, from Nippon Dental University, Japan, used stem cells from dental pulp - the central part of the tooth made up of connective tissue and cells - which were obtained from the teeth of dental patients who were undergoing routine tooth extractions.

Once the cells were sufficiently prepared, they were separated into two batches (a test and a control) and the test cells incubated in a H2S chamber.

They were harvested and analysed after 3, 6 and 9 days to see if the cells had successfully transformed into liver cells.

To test if the cells successfully differentiated under the influence of H2S, the researchers carried out a series of tests looking at features that were characteristic of liver cells.

In addition to physical observations under the microscope, the researchers investigated the cell's ability to store glycogen and then recorded the amount of urea contained in the cell.

"Until now, nobody has produced the protocol to regenerate such a huge number of hepatic cells for human transplantation. Compared to the traditional method of using fetal bovine serum to produce the cells, our method is productive and, most importantly, safe," Dr. Yaegaki added.

Hydrogen sulphide (H2S) has the characteristic smell of rotten eggs and is produced throughout the body in the tissues.

Although its exact function is unknown, researchers have been led to believe that it plays a key role in many physiological processes and disease states.

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

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'Bad breath' chemical may fuel development of dental pulp stem cells

Report says women have egg-producing stem cells

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Report says women have egg-producing stem cells

Rare stem cells may produce new eggs, scientists 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.

 

Link:
Rare stem cells may produce new eggs, scientists say

Ovarian Stem Cells Make Human Eggs in Possible Aid to Fertility

February 27, 2012, 12:41 AM EST

By Ryan Flinn

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

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

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

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

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

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

7-Million Eggs

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

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

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

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

‘Practical Applications”

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

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

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

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

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

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

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

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

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

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Ovarian Stem Cells Make Human Eggs in Possible Aid to Fertility

Gene may be culprit in SIDS for boys

Sudden infant death syndrome (SIDS) may sometimes have a genetic component, a team of German researchers reports.

DNA analysis from a small group of infants who succumbed to SIDS revealed that many of the male children carried a particular enzyme mutation that may have impaired their ability to breath properly. This was not the case for female SIDS patients.

Study author Dr. Michael Klintschar, director of the Institute for Legal Medicine at Medical University Hannover in Germany, said his team tried to build upon previous research suggesting that "abnormalities in the brain stem, the part of the brain that regulates breathing and other basic functions, lead to SIDS."

"The reasons for these abnormalities are unclear," he noted, "but some scientists believe that the genes inherited by the parents might be one of several factors."

Klintschar and his colleagues found indications that SIDS risk might be higher among male infants who carry a mutation of an enzyme -- called MAOA -- that appears to impede key neurotransmitter function.

"Babies that have this variant inherited might have an impaired breathing regulation," he said. "But the risk conveyed by this gene variant is relatively small compared to other factors, like sleeping position (or exposure to) smoking. Moreover, the findings have to be replicated in another population sample."

The study appears online and in the March issue of Pediatrics.

The authors noted that SIDS is one of the great mysteries in pediatric medicine, with efforts to pin down the root cause for the sudden loss of children under the age of 1 year falling short of a definitive answer.

The new study focused on 156 white infants (99 boys and 57 girls) who were born in the Lower Saxony region of Germany and died while sleeping.

The deaths took place between the second and the 51st week of life, and all remained "unexplained" despite full autopsies, clinical history reviews and analyses of the circumstances of death.

DNA samples were taken from all the deceased, as well as from another 260 male adults between the ages of 18 and 30.

The result: MAOA mutations were more commonly found among male SIDS children than among their healthy male counterparts. This did not hold true with female SIDS children.

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Gene may be culprit in SIDS for boys

Osamu Honmou, “Transplantation of bone marrow stem cells” – Video

22-02-2012 04:19 Osamu Honmou, Sapporo Medical University, Sapporo, "Transplantation of bone marrow stem cells" at the International Conference of Stem Cells and Regenerative Medicine for Neurodegenerative Diseases to be held at the Tzu-Chi Hospital in Hualien, Taiwan on April 22-24, 2010.

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Osamu Honmou, "Transplantation of bone marrow stem cells" - Video

Dental pulp stem cells transformed by ‘bad breath’ chemical

Public release date: 26-Feb-2012
[ | E-mail | Share ]

Contact: Joe Winters
joseph.winters@iop.org
44-794-632-1473
Institute of Physics

Japanese scientists have found that the odorous compound responsible for halitosis ? otherwise known as bad breath ? is ideal for harvesting stem cells taken from human dental pulp.

In a study published today, Monday 27 February, in IOP Publishing's Journal of Breath Research, researchers showed that hydrogen sulphide (H2S) increased the ability of adult stem cells to differentiate into hepatic (liver) cells, furthering their reputation as a reliable source for future liver-cell therapy.

This is the first time that liver cells have been produced from human dental pulp and, even more impressively, have been produced in high numbers of high purity.

"High purity means there are less 'wrong cells' that are being differentiated to other tissues, or remaining as stem cells. Moreover, these facts suggest that patients undergoing transplantation with the hepatic cells may have almost no possibility of developing teratomas or cancers, as can be the case when using bone marrow stem cells," said lead author of the study Dr. Ken Yaegaki.

The remarkable transforming ability of stem cells has led to significant focus from research groups around the world and given rise to expectations of cures for numerable diseases, including Parkinson's and Alzheimer's.

In this study, Dr. Ken Yaegaki and his group, from Nippon Dental University, Japan, used stem cells from dental pulp ? the central part of the tooth made up of connective tissue and cells ? which were obtained from the teeth of dental patients who were undergoing routine tooth extractions.

Once the cells were sufficiently prepared, they were separated into two batches (a test and a control) and the test cells incubated in a H2S chamber. They were harvested and analysed after 3, 6 and 9 days to see if the cells had successfully transformed into liver cells.

To test if the cells successfully differentiated under the influence of H2S, the researchers carried out a series of tests looking at features that were characteristic of liver cells. In addition to physical observations under the microscope, the researchers investigated the cell's ability to store glycogen and then recorded the amount of urea contained in the cell.

"Until now, nobody has produced the protocol to regenerate such a huge number of hepatic cells for human transplantation. Compared to the traditional method of using fetal bovine serum to produce the cells, our method is productive and, most importantly, safe" continued Dr. Yaegaki.

Hydrogen sulphide (H2S) has the characteristic smell of rotten eggs and is produced throughout the body in the tissues. Although its exact function is unknown, researchers have been led to believe that it plays a key role in many physiological processes and disease states.

###

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

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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

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Dental pulp stem cells transformed by 'bad breath' chemical

Under the Microscope #10 – Video

20-02-2012 04:06 (Watch in 720p if possible) Here we can see the underside of mouse tail skin. Under the Microscope is a collection of videos that show glimpses of the natural and man-made world in stunning close-up. They are released every Monday and Thursday and you can see them here: bit.ly Claire Cox: "The epidermis, which is the outer layer of mammalian skin, is maintained by numerous stem cell populations. The identification of the factors involved in controlling these populations and thus epidermal maintenance is highly valuable. Not only will it provide information as to how a complex tissue is organised and controlled, the principles that are learnt can be applied to other tissues. Through the work that I am completing, I hope that I can also gain a perspective as to what goes wrong in disease processes such as skin cancer. Skin cancer is one of the most prevalent cancers in the world, and understanding what goes wrong and the factors involved could potentially lead to new ideas as to prevention and treatment." The image is 700µm in width - this is about the size of the full stop in this sentence. About 5000 cells would fit on the surface of a full stop. Many thanks to: Dr Michaela Frye, Frye Lab members, Peter Humphreys, Margaret McLeish. More info: Wellcome Trust Centre For Stem Cell Research http://www.cscr.cam.ac.uk Department of Physiology Development and Neuroscience http Claire Cox's profile: http://www.cscr.cam.ac.uk Graduate School of Life Sciences and its annual Poster and Image ...

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Under the Microscope #10 - Video

Report says women have egg-producing stem cells

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Report says women have egg-producing stem cells

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24-02-2012 13:31 Spinal Cord Injury - http://www.projectwalk.org exists to provide an improved quality of life for people with spinal cord injuries through intense exercise-based recovery programs, education, support and encouragement.

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Researchers used stem cells to produce human eggs

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

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Researchers used stem cells to produce human eggs

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. 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.

See the original post here:
Report: Stem cells may create new eggs

Ovary stem cells can produce new eggs, researchers say

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

Ogden family at center of ethics debate in genetics research

Ogden • By the time Camilla Black Grondahl became pregnant with her second child in 2010, she had already watched two older sisters bury sons who were born with a congenital affliction that gave them the appearance of “little old men.” Various health problems made their survival impossible.

The young mother did not know whether she, too, could pass the condition to her unborn son. But a Utah researcher, who had been sequencing her family’s genes, did know.

Gholson Lyon’s research team had detected a mutation in her genome that gave any boy she conceived a 50-50 chance of sharing the heartbreaking fate of his cousins and two uncles.

“My jaw dropped open. Who would have thought that another mother would get pregnant during this research and it would be a boy?” said Lyon, then a professor of psychiatry leading the University of Utah’s genetic research into the disease.

He found himself in an ethical quandary that is bound to become more common in biomedical research. As technology advances and costs come down, gene sequencing is becoming routine — yet no system is in place to alert study volunteers about results that could have crucial bearing on their health.

Lyon is a physician, but he was not comfortable with warning the Grondahl family. He was not Camilla Grondahl’s doctor. And the gene sequencing, like almost all testing done for biomedical research, was not done in a clinically certified manner.

What if the data were wrong and the young woman terminated her pregnancy?

Nor was he comfortable not sharing the results with the family, who had welcomed him into their home.

Story continues below

Last February, the Grondahls’ son Max was born with the telltale signs of the then-unknown disease: wrinkled skin, hernias and facial deformities. By the time “our valiant hero,” as his parents called Max, died four months later, U. researchers had a name for the disease: Ogden syndrome.

In a commentary published this week in the top-shelf science journal Nature, Lyon describes the ethical dilemma that he and other genetic researchers face when they find genes with medical consequences for those they are studying.

“At the moment, human-genetics researchers operate in a totally unregulated environment, following their own protocols to obtain, store, track and analyze DNA — creating many opportunities for error,” Lyon wrote. “But when the result can mean the difference between life and death, mistakes are not an option.”

He proposes requiring that all sequencing of human genes follow strict federal guidelines known as Clinical Laboratory Improvement Amendments, or CLIA. The move would add physicians to each study, who would order certified testing and ensure volunteers received genetic counseling to explain the results.

“In this way, when participants want to know what we know, we will feel confident that what we tell them is correct,” wrote Lyon, now a research scientist at the Children’s Hospital of Philadelphia. Next month, he is moving to Cold Spring Harbor Laboratory, a leading genetics research institution on Long Island.

But Lyon concedes there are no simple answers, although he believes his proposal could save society money in the long run since the resulting information could prevent disease in some cases and improve treatment outcomes in others. And sequencing DNA in centralized certified-facilities could be less costly, thanks to economies of scale, and avoid unnecessary duplication of sequencing.

But if all laboratories that might make discoveries related to volunteers’ health were required to be CLIA-certified, research costs could be driven up, said Lynn Jorde, the chairman of the U.’s human genetics department and the past president of the American Society of Human Genetics.

“It would cost a great deal of extra money,” Jorde said, “at a time when research funding is rapidly vanishing.”

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Ogden family at center of ethics debate in genetics research

Dental pulp stem cells transformed by 'bad breath' chemical

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

Japanese scientists have found that the odorous compound responsible for halitosis ? otherwise known as bad breath ? is ideal for harvesting stem cells taken from human dental pulp.

In a study published today, Monday 27 February, in IOP Publishing's Journal of Breath Research, researchers showed that hydrogen sulphide (H2S) increased the ability of adult stem cells to differentiate into hepatic (liver) cells, furthering their reputation as a reliable source for future liver-cell therapy.

This is the first time that liver cells have been produced from human dental pulp and, even more impressively, have been produced in high numbers of high purity.

"High purity means there are less 'wrong cells' that are being differentiated to other tissues, or remaining as stem cells. Moreover, these facts suggest that patients undergoing transplantation with the hepatic cells may have almost no possibility of developing teratomas or cancers, as can be the case when using bone marrow stem cells," said lead author of the study Dr. Ken Yaegaki.

The remarkable transforming ability of stem cells has led to significant focus from research groups around the world and given rise to expectations of cures for numerable diseases, including Parkinson's and Alzheimer's.

In this study, Dr. Ken Yaegaki and his group, from Nippon Dental University, Japan, used stem cells from dental pulp ? the central part of the tooth made up of connective tissue and cells ? which were obtained from the teeth of dental patients who were undergoing routine tooth extractions.

Once the cells were sufficiently prepared, they were separated into two batches (a test and a control) and the test cells incubated in a H2S chamber. They were harvested and analysed after 3, 6 and 9 days to see if the cells had successfully transformed into liver cells.

To test if the cells successfully differentiated under the influence of H2S, the researchers carried out a series of tests looking at features that were characteristic of liver cells. In addition to physical observations under the microscope, the researchers investigated the cell's ability to store glycogen and then recorded the amount of urea contained in the cell.

"Until now, nobody has produced the protocol to regenerate such a huge number of hepatic cells for human transplantation. Compared to the traditional method of using fetal bovine serum to produce the cells, our method is productive and, most importantly, safe" continued Dr. Yaegaki.

Hydrogen sulphide (H2S) has the characteristic smell of rotten eggs and is produced throughout the body in the tissues. Although its exact function is unknown, researchers have been led to believe that it plays a key role in many physiological processes and disease states.

###

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

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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Go here to see the original:
Dental pulp stem cells transformed by 'bad breath' chemical

Study says women's ovaries harbour rare egg-producing stem cells, a step in fertility research

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 harbour 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 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.

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.

Go here to see the original:
Study says women's ovaries harbour rare egg-producing stem cells, a step in fertility research

Women have rare egg-producing stem cells

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 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.

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

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Women have rare egg-producing stem cells

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

###

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

The study was supported by a 10-year MERIT Award to Tilly from the National Institute on Aging, a Ruth L. Kirschstein National Research Service Award from the National Institutes of Health, the Henry and Vivian Rosenberg Philanthropic Fund, the Sea Breeze Foundation, and Vincent Memorial Hospital Research Funds. Tilly is a co-founder of OvaScience, Inc. (www.ovascience.com), which has licensed the commercial potential of these and other patent-protected findings of the MGH-Vincent team for development of new fertility-enhancing procedures.

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

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

Pioneering lab work aims to smash women's fertility barrier

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.

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Pioneering lab work aims to smash women's fertility barrier

Report: Women have rare egg-producing stem cells

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.

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Report: Women have rare egg-producing stem cells

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