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U-M Human Embryonic Stem Cell Line Placed On National Registry for Researchers

To: EDUCATION, MEDICAL AND NATIONAL EDITORS

Line is first from U-M accepted to the U.S. National Institutes of Health registry, now available for federally-funded research

ANN ARBOR, Mich., Feb. 14, 2012 /PRNewswire-USNewswire/ -- The University of Michigan's first human embryonic stem cell line will be placed on the U.S. National Institutes of Health's registry, making the cells available for federally-funded research. It is the first of the stem cell lines derived at the University of Michigan to be placed on the registry.

The line, known as UM4-6, is a genetically normal line, derived in October 2010 from a cluster of about 30 cells removed from a donated five-day-old embryo roughly the size of the period at the end of this sentence. That embryo was created for reproduction but was no longer needed for that purpose and was therefore about to be discarded.

"This is significant, because acceptance of these cells on the registry demonstrates our attention to details of proper oversight, consenting, and following of NIH guidelines established in 2009," says Gary Smith, Ph.D., who derived the line and also is co-director of the U-M Consortium for Stem Cell Therapies, part of the A. Alfred Taubman Medical Research Institute.

"It now makes the line available to researchers who can apply for federal funding to use it in their work; this is an important step."

The line is the culmination of years of planning and preparation and was made possible by Michigan voters' November 2008 approval of a state constitutional amendment permitting scientists here to derive embryonic stem cell lines using surplus embryos from fertility clinics or embryos with genetic abnormalities and not suitable for implantation.

"We expect these cells will be used by investigators worldwide to enhance our understanding of stem cell biology, and together with disease-specific lines, discover treatments and cures for genetic diseases," says Smith, who is a professor in the Department of Obstetrics and Gynecology at the University of Michigan Medical School.

U-M is among just a handful of U.S. universities creating human embryonic stem cell lines. There are only 147 stem cell lines available on the registry.

"We envision in the future that investigators will be able to use the genetically normal embryonic stem cell lines like UM4-6, together with disease-specific embryonic stem cell lines, as a model system to investigate what causes these diseases and come up with treatments," says Sue O'Shea, professor of Cell and Developmental Biology, and co-director of the Consortium for Stem Cell Therapies.

U-M also has two other human embryonic stem cells lines submitted to the national registry. Both are disease specific, the first carrying the genetic defect that causes hemophilia B, and the other carries the gene responsible for Charcot-Marie-Tooth disease, a hereditary neurological disorder.

Smith expects to soon submit eight additional human embryonic stem lines for consideration on the national registry: three genetically normal and five new disease specific lines.

This is a historic achievement that will lead to treatments and cures for serious, life-altering diseases and is more evidence that our University of Michigan researchers are leading the world in cutting-edge science that will impact health around the globe, says Eva Feldman, M.D., Ph.D., director of the A. Alfred Taubman Medical Research Institute.

"This is another major step forward for medical science in Michigan. This opens us another avenue for researchers to really begin exploring the causes and progression of those diseases, with the ultimate goal of finding new therapies for patients," says Feldman.

Contributors to the A. Alfred Taubman Medical Research Institute's Consortium for Stem Cell Therapies include the Taubman Institute; the Office of the Executive Vice President for Medical Affairs; the Office of the Medical School Dean; the Comprehensive Cancer Center; the Department of Pediatrics and Communicable Diseases; the Office of the Vice President for Research; the School of Dentistry; the Department of Pathology; the Department of Cell and Developmental Biology; the College of Engineering; the Life Sciences Institute; the Department of Neurology; and U-M's Michigan Institute for Clinical and Health Research.

A. Alfred Taubman, founder and chair of U-M's Taubman Institute, called the registry placement a tremendous step for stem cell research.

"I consider stem cells to be a modern medical miracle - the most exciting advance in medicine since antibiotics. The progress we have made throughout the state in stem cell research has been nothing short of remarkable," says Taubman.

"This milestone means much to the University of Michigan and the state of Michigan, but also to the world. It offers another route for researchers to move ahead in studying these horrible diseases. We hope it is the first of many lines that the University of Michigan can contribute to the global efforts to improve human health."

For more information about the A. Alfred Taubman Medical Research Institute at the University of Michigan Medical School, visit http://www.taubmaninstitute.org

For more information about stem cell research at U-M, visit http://www.umich.edu/stemcell

SOURCE University of Michigan Health System

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U-M human embryonic stem cell line placed on national registry

Public release date: 14-Feb-2012
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Contact: Mary F. Masson
mfmasson@umich.edu
734-764-2220
University of Michigan Health System

ANN ARBOR, Mich. ? The University of Michigan's first human embryonic stem cell line will be placed on the U.S. National Institutes of Health's registry, making the cells available for federally-funded research. It is the first of the stem cell lines derived at the University of Michigan to be placed on the registry.

The line, known as UM4-6, is a genetically normal line, derived in October 2010 from a cluster of about 30 cells removed from a donated five-day-old embryo roughly the size of the period at the end of this sentence. That embryo was created for reproduction but was no longer needed for that purpose and was therefore about to be discarded.

"This is significant, because acceptance of these cells on the registry demonstrates our attention to details of proper oversight, consenting, and following of NIH guidelines established in 2009," says Gary Smith, Ph.D., who derived the line and also is co-director of the U-M Consortium for Stem Cell Therapies, part of the A. Alfred Taubman Medical Research Institute.

"It now makes the line available to researchers who can apply for federal funding to use it in their work; this is an important step."

The line is the culmination of years of planning and preparation and was made possible by Michigan voters' November 2008 approval of a state constitutional amendment permitting scientists here to derive embryonic stem cell lines using surplus embryos from fertility clinics or embryos with genetic abnormalities and not suitable for implantation.

"We expect these cells will be used by investigators worldwide to enhance our understanding of stem cell biology, and together with disease-specific lines, discover treatments and cures for genetic diseases," says Smith, who is a professor in the Department of Obstetrics and Gynecology at the University of Michigan Medical School.

U-M is among just a handful of U.S. universities creating human embryonic stem cell lines. There are only 147 stem cell lines available on the registry.

"We envision in the future that investigators will be able to use the genetically normal embryonic stem cell lines like UM4-6, together with disease-specific embryonic stem cell lines, as a model system to investigate what causes these diseases and come up with treatments," says Sue O'Shea, professor of Cell and Developmental Biology, and co-director of the Consortium for Stem Cell Therapies.

U-M also has two other human embryonic stem cells lines submitted to the national registry. Both are disease specific, the first carrying the genetic defect that causes hemophilia B, and the other carries the gene responsible for Charcot-Marie-Tooth disease, a hereditary neurological disorder.

Smith expects to soon submit eight additional human embryonic stem lines for consideration on the national registry: three genetically normal and five new disease specific lines.

This is a historic achievement that will lead to treatments and cures for serious, life-altering diseases and is more evidence that our University of Michigan researchers are leading the world in cutting-edge science that will impact health around the globe, says Eva Feldman, M.D., Ph.D., director of the A. Alfred Taubman Medical Research Institute.

"This is another major step forward for medical science in Michigan. This opens us another avenue for researchers to really begin exploring the causes and progression of those diseases, with the ultimate goal of finding new therapies for patients," says Feldman.

Contributors to the A. Alfred Taubman Medical Research Institute's Consortium for Stem Cell Therapies include the Taubman Institute; the Office of the Executive Vice President for Medical Affairs; the Office of the Medical School Dean; the Comprehensive Cancer Center; the Department of Pediatrics and Communicable Diseases; the Office of the Vice President for Research; the School of Dentistry; the Department of Pathology; the Department of Cell and Developmental Biology; the College of Engineering; the Life Sciences Institute; the Department of Neurology; and U-M's Michigan Institute for Clinical and Health Research.

A. Alfred Taubman, founder and chair of U-M's Taubman Institute, called the registry placement a tremendous step for stem cell research.

"I consider stem cells to be a modern medical miracle ? the most exciting advance in medicine since antibiotics. The progress we have made throughout the state in stem cell research has been nothing short of remarkable," says Taubman.

"This milestone means much to the University of Michigan and the state of Michigan, but also to the world. It offers another route for researchers to move ahead in studying these horrible diseases. We hope it is the first of many lines that the University of Michigan can contribute to the global efforts to improve human health."

###

For more information about the A. Alfred Taubman Medical Research Institute at the University of Michigan Medical School, visit http://www.taubmaninstitute.org

For more information about stem cell research at U-M, visit http://www.umich.edu/stemcell


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Scientists concerned about antibiotic resistance in wastewater

by Stephanie Hemphill, Minnesota Public Radio

February 9, 2012

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St. Paul, Minn. — Scientists gather in St. Paul today to discuss a category of pollution called emerging contaminants — new substances they don't know enough about to label harmful to the environment and human health.

Researchers are particularly troubled by a contaminant that may flourish in wastewater treatment plants: antibiotic-resistant bacteria. Antibiotics are now so widely used — in medicine, in agriculture and cleaning products — that some bacteria are quickly evolving to defy treatment for deadly diseases.

Designed to protect the environment, wastewater treatment plants have dramatically cleaned up many rivers that were once open drains for human waste. They typically employ beneficial bacteria to consume wastes. But researchers say the bacteria used in the plants may be mixing with harmful bacteria.

"The idea is the bad bacteria generally die off," said Amy Pruden, an associate professor of civil and environmental engineering at Virginia Tech. "But the good bacteria are flourishing, and might be able pick up that genetic material, and then propagate it, and then it becomes a reservoir, and increases just the whole background pool of resistance that can go out in the environment and be a potential source of exposure."

Pruden said researchers are concerned about new strains of bacteria because people are showing up in emergency rooms with resistant infections for which doctors cannot identify a source.

She said her research shows the mix of good and bad bacteria in wastewater treatment plants probably creates bacteria that cannot be controlled with antibiotics.

Among the places scientists are studying is Duluth's treatment plant on the St. Louis River, located between Lake Superior, with its vast stretch of clean water, and an area upstream of the plant where the river bank is mostly undeveloped.

Timothy LaPara, an environmental engineer at the University of Minnesota, took water samples in several places to pinpoint where antibiotic-resistant bacteria were present at elevated levels.

"What we saw was resistance was very low upstream of the city," LePara said. "In the harbor it was higher, in the wastewater outfall it was much higher, and then out in Lake Superior it was very low again, which allowed us to — with a great deal of certainty — conclude that the wastewater treatment outfall was the primary source of antibiotic-resistant genes in the harbor."

One gene linked to antibiotic resistance was 20-times as common in the outflow of the treatment plant as in other samples.

LaPara said the bacteria-resistant genes can be captured by filtering the water thoroughly.

The Duluth plant uses a filter of anthracite coal, silica sand, fine garnet and gravel to trap harmful wastes.

La Para said that if resistant genes survive the multi-stage filter, other wastewater treatment plants probably are also creating pools of antibiotic-resistant bacteria. Most treatment plants in the United States don't have that level of treatment, he said.

If so, people could be exposed to such bad bugs by swimming in rivers and lakes where treatment plants discharge water, or even by drinking tap water.

Duluth gets its drinking water from Lake Superior. It is treated thoroughly, but La Para said tiny amounts of antibiotic-resistant material have been detected in drinking water in other studies.

La Para said the research is just beginning. He said scientists must assess how much of a threat the substances might pose to human health.

"Our technologies have gotten so good to detect a lot of these compounds," La Para said. "It's now a question of when does the risk become so significant that we want to further remove them? Is it a part per billion? A part per trillion?"

More research is needed to determine that risk, La Para and Pruden said. In the meantime, they say wastewater treatment plants could consider adding another layer of treatment such as membrane filters or chemicals to kill all the organisms.

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Siemens partners with drugmakers

SAN FRANCISCO – Siemens, Europe’s largest engineering company, is wading into the multibillion-dollar field of personalized medicine by announcing deals to develop companion tests with two drugmakers.

The Munich-based company will work with HIV drugmaker ViiV Healthcare and Tocagen, developer of an experimental brain tumor treatment, to create tests that determine which patients will benefit from the therapies, said Trevor Hawkins, head of Siemens’ next-generation diagnostics division.

“This is a major step forward for us, moving into this multibillion market, which we haven’t been in up until today,” Hawkins said in an interview last week.

Personalized medicine involves determining whether a patient is genetically susceptible to a particular disease or would be especially responsive to certain treatments. These new therapies often require special genetic tests, which are being created by separate companies, in some cases.

The market for molecular diagnostics, which includes personalized medicine tests, will more than double in the U.S. to $5.5 billion in 2016 from $2.5 billion in 2010, according to TriMarkPublications.com.

ViiV, a venture between London-based GlaxoSmithKline and New York-based Pfizer , the world’s biggest drugmaker, has an HIV drug called Selzentry that works with patients who have a specific form of the virus. Siemens will develop a test to help doctors determine which patients would benefit from the therapy.

Tocagen, based in San Diego, is working on a treatment for glioma, or brain cancer, called Toca 511 that’s in early human trials. Working with Siemens will give the company more credibility in discussions with the Food and Drug Administration, said Harry Gruber, chief executive officer of closely held Tocagen.

Siemens, Roche and Abbott Laboratories are seeking to form partnerships with drugmakers to develop these companion tests, said David Parker, vice president of the consulting firm Boston Healthcare.

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Not as Easy as it Sounds

The President's Council of Advisors on Science and Technology recently published a new report with seemingly simple recommendations to improve the state of science education in the US, reports ScienceInsider's Jeffrey Mervis. But educators say the recommendations are deceptively simple, and will actually be challenging to implement. PCAST's report says improving undergraduate education in STEM fields is a matter of making introductory courses more interesting and more active, and helping students find jobs in science and engineering, among other suggestions, Mervis says. However, the implementation of these recommendations will require changes in academic culture, according to experts.

"Education reformers say one of their biggest hurdles is an academic culture that prizes research over teaching and that traditionally has been geared more toward weeding out rather than attracting students into majoring in STEM fields," Mervis says. "In addition, the current system of US higher education, including community colleges and 4-year institutions as well as those offering graduate degrees in STEM fields, is so vast that it is inherently resistant to change."

The authors of the report say that their recommendations, if implemented, could result in a million additional students graduating with STEM degrees. In accordance with this report, the Obama administration has proposed spending $60 million on research into the best approaches to improve science and math education in the US, Mervis adds.

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Lab-Made Neurons Allow Scientists To Study A Genetic Cause Of Parkinson's

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Academic Journal
Main Category: Parkinson's Disease
Also Included In: Neurology / Neuroscience
Article Date: 09 Feb 2012 - 0:00 PST

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By reverse engineering human skin cells to become induced pluripotent stem cells (iPSCs) and then coaxing them to become neural dopamine cells, scientists in the US have developed a way to study a genetic cause of Parkinson's disease in lab-made neurons. Their findings, which they write about in the 7 February issue of Nature Communications, reveal some potential new drug targets for Parkinson's and a new platform to screen treatments that might mimic the protective functions of parkin, the gene they investigated.

Parkinson's disease is a progressive neurological disorder that results from the death of dopamine-secreting neurons in a region of the brain that controls movement. In the US there are 500,000 people with Parkinson's disease, and 50,000 new cases every year. There is no cure.

Most cases have no specific cause, but around 1 in 10 can be attributed to known genetic factors. One of these is mutations in the parkin gene.

To study the effect of the parkin gene in brain cells, you have to study live human neurons. But they are hard to study because they live in complex networks in the brain, ruling out the possibility of extracting them.

And you can't use animals, because when they lack the parkin gene, they don't develop Parkinson's disease: human neurons are thought to have "unique vulnerabilities" in this respect.

(The suggestion is that the larger human brain uses more dopamine to support the neural computation that is needed to enable us to walk on two legs, compared to the four-legged movement of almost all other animals.)

But in 2007, scientists in Japan described how they made human stem cells (iPSCs) without using embryos, and since then, lead author of the Nature Communications study, Dr Jian Feng from the University at Buffalo (UB) in New York, and colleagues, have been looking for a way to use the technology to study neurons with mutations in the parkin gene.

Feng, a professor of physiology and biophysics in the UB School of Medicine and Biomedical Sciences, said in a press statement that the advent of iPSCs was a "game-changer" for their field of work:

"Before this, we didn't even think about being able to study the disease in human neurons."

"The brain is so fully integrated. It's impossible to obtain live human neurons to study," he added.

For their study, Feng and colleagues reverse engineered human skin cells to make iPSCs. The skin cells came from four people: two with a rare type of Parkinson's disease where parkin causes the disease, and two healthy people who served as controls.

"Once parkin is mutated, it can no longer precisely control the action of dopamine, which supports the neural computation required for our movement," said Feng.

Feng and colleagues also found that mutations in parkin stop it being able to tightly control the production of monoamine oxidase (MAO), which catalyzes dopamine oxidation.

"Normally, parkin makes sure that MAO, which can be toxic, is expressed at a very low level so that dopamine oxidation is under control," said Feng.

But they found that when it is mutated, parkin loses the ability to regulate MAO, so the level goes up.

"The nerve cells from our Parkinson's patients had much higher levels of MAO expression than those from our controls. We suggest in our study that it might be possible to design a new class of drugs that would dial down the expression level of MAO," explained Feng, who noted that one of the drugs currently used to treat Parkinson's disease slows the activity of MAO and in trials has been shown to slow disease progression.

Fend said they discovered that a key reason for the death of dopamine neurons was oxidative stress due to there being too much MAO around. But before the neurons die, the precise action of dopamine in helping the neural computations that support movement, is disrupted by mutations in parkin.

"This paper provides the first clues about what the parkin gene is doing in healthy controls and what it fails to achieve in Parkinson's patients," said Feng.

When the researchers delivered normal parkin into the neurons with the mutations, the defects were reversed. This is what makes them think such neurons could be used as a platform for screening new drug candidates that could mimic the protective effect of normal parkin.

The University of Buffalo has applied for patent protection on the screening platform.

Although parkin mutations are responsible for a small proportion of Parkinson's cases, the researchers believe that understanding how the gene works could be relevant to all cases of the disease.

Written by Catharine Paddock PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Visit our parkinson's disease section for the latest news on this subject. "Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells"; Houbo Jiang, Yong Ren, Eunice Y. Yuen, Ping Zhong, Mahboobe Ghaedi, Zhixing Hu, Gissou Azabdaftari, Kazuhiro Nakaso, Zhen Yan & Jian Feng; Nature Communications 3:668; Published online 07 Feb 2012; DOI:10.1038/ncomms1669; Link to Abstract.
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