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Researchers Report Stem Cell Advance

By Jeffrey Perkel

HealthDay Reporter
Thursday, September 25, 2008; 12:00 AM

THURSDAY, Sept. 25 (HealthDay News) — Researchers report that they have sidestepped a major technical hurdle in the generation of pluripotent stem cells from adult cells.

A team of Boston scientists developed a way to generate induced pluripotent stem cells (iPS) — which are functionally similar to embryonic stem cells, but which can be produced from adult cells, rather than via the creation or destruction of an embryo — more safely than ever.

Should the findings, which involved mouse cells, be repeated with humans,

they could pave the way for using iPS to delve into the biology of a wide range of genetic diseases. Longer term, they could lead to patient-specific stem-cell therapies.

“I think it’s a really important, landmark study,” said Kevin Eggan, an assistant professor of Stem Cell and Regenerative Biology and an assistant investigator of the Stowers Medical Institute at Harvard University. He was not involved in the study.

The results were published in the Sept. 25 online edition ofScience.

Shinya Yamanaka, of Kyoto University, Japan, first demonstrated in 2006 that adult mouse cells — for instance, skin cells — could be reprogrammed into something akin to an embryonic stem cell by the introduction of four specific genes. According to the lead author of this latest study, Matthias Stadtfeld, that “was like a gigantic, essentially quantum leap for biology.” The following year, Yamanaka and James Thomson, of the University of Wisconsin, Madison, demonstrated the same approach could create human iPS cells.

Normally, the four genes — all of which can induce cancer if left unchecked — are delivered using retroviruses, which integrate their viral DNA into the cells’ chromosomes; the worry is that these random insertions will introduce mutations into the cells that would alter their behavior, thus minimizing the cells’ potential usefulness as research tools. Should these cells ever be used to generate tissues that were transplanted into human patients, researchers fear they could inadvertently lead to cancer.

Konrad Hochedlinger, of Massachusetts General Hospital and the Harvard Stem Cell Institute, his postdoctoral fellow Stadtfeld, and their colleagues circumvented this problem by delivering the genes using adenoviruses instead, which do not insert their viral DNA into a cell’s chromosomes. iPS cells generated by this new approach appear indistinguishable from other iPS cells, carry some of the molecular hallmarks of embryonic stem cells, and can form multiple cell types when transplanted into mice (that is, they are pluripotent).

“My conclusion is that viral integration is not necessary for reprogramming to a pluripotent state, which is an important step toward safer patient-specific iPS cells, if it can be translated into humans,” said Stadtfeld.

Human iPS cells have several potential applications. On a research level, they may be used to study how particular genetic defects lead to disease. Pharmaceutical companies might be able to use these cells to design drugs that alter, circumvent or repair these behaviors. Ultimately, iPS cells could be used clinically to develop patient-specific transplants, for instance, of genetically repaired neurons in patients with neurodegenerative diseases.

Before any of that can happen, however, this new method must be optimized. Only about one in 1 million skin cells actually developed into an iPS by Stadtfeld’s method, compared to one in 10,000 using retroviruses. Using liver cells (hepatocytes), the efficiency was about one in 50,000 — better, but still worse than with retroviruses.

“For this to be translated into humans, we have to find ways to make the process more efficient and properly make it work in cell types which are more easily accessible than hepatocytes, such as skin cells, for example,” said Stadtfeld.

Dr. Rudolf Jaenisch, of the Whitehead Institute and Massachusetts Institute of Technology, who studies iPS cells, called the findings “clearly an advance.”

“They show that, although very inefficiently, they can get iPS cells, which apparently don’t have any genetic alterations,” he said.

Though he praised the study, Eggan noted several caveats. First, though adenoviruses do not normally integrate their DNA into the host cell’s chromosomes, sometimes they do. “There’s always going to be this lingering possibility that it can happen in some cases,” he said.

Yet Eggan also said that, given the success of this study, researchers may ultimately find that they can reprogram adult cells into iPS cells without using viruses at all, for instance, with chemicals or by delivering pure RNAs instead.

“All sorts of things like this become more of a reality due to the success of this experiment,” he said.

Eggan’s second caveat was that, despite their apparent similarity, iPS cells are not embryonic stem cells. It remains an open question as to whether the two are functionally equivalent.

“There are a variety of fundamental issues which haven’t been well addressed about the equivalence of iPS and embryonic stem cells,” he said, “I cannot say that strongly enough.”

For instance, no one has yet been able to grow a mouse from a single iPS cell — what Eggan calls the “gold standard” assay of embryonic stem cell pluripotency — and not for lack of trying, he said.

Questions aside, Stadtfeld said he anticipates no problems translating these findings to human cells, aside from the fact that human embryonic stem cell culture is inherently trickier than its murine counterpart.

“I believe it will be a technical hurdle, but I would expect people would take the hurdle in the next half-year or year — probably half-year,” he said. Then he added, “I think maybe people have taken the hurdle already. It’s possible.”

More information

For more about stem cells, visit the National Institutes of Health.

SOURCES: Matthias Stadtfeld, Ph.D., postdoctoral fellow, Massachusetts General Hospital Cancer Center and Harvard Stem Cell Institute, Boston;

Kevin Eggan Ph.D., assistant professor, Stem Cell and Regenerative Biology, and assistant investigator, Stowers Medical Institute, Harvard University; Rudolf Jaenisch, M.D., professor, biology, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology; Sept. 25, 2008,Science

Washingtonpost.com

September 28th 2008 Posted to Stem Cells, BioBanks, Biomedical Ethics, Fall 2008

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Personal Genetics Education Project - Tools for teachers

This series of lesson plans is intended to faciliate the inclusion of ethics and personal genomes in the high school and college classroom. Each unit can function as a stand-alone lesson, or all units can be taught as a series. Lessons include a set of PowerPoint slides, suggestions for further reading, and materials for in-class and homework activities.

At http://genepath.med.harvard.edu/WuLab/pgEd/curricula.html

September 11th 2008 Posted to Cloning, DNA Test & Personalized Medicine, Reproductive Medicine, Stem Cells, BioBanks, US, Health & Insurance & Privacy, Fall 2008

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Rep. Kennedy Revives Obama’s Personalized Medicine Bill for Next Congress; Adds Incentives

September 10, 2008 By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – A bill in this year’s US Congress that aimed to advance personalized medicine and pharmacogenomics will be replaced in the upcoming 111the Congress by another bill that includes a new tax incentive for personalized medicine research.

The Genomics and Personalized Medicine Act of 2008 (H.R.6498), introduced by Rep. Patrick Kennedy (D – RI), adds to the language of Senator Barack Obama’s (D – Ill.) 2007 version new tax and test credit incentives to lure researchers into the field. The bill has been introduced and has been referred to the House Ways and Means Committee and to the House Energy and Commerce Committee.

The Obama and the Kennedy bills share the same core four-part focus.

First, the act would create a Genomics and Personalized Medicine Interagency Working Group that would include the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, and other groups outside of the Department of Health and Human Services.

It also would start a National Biobanking Initiative that would create a database for collecting and integrating genomics data with environmental and clinical health information. It also would use funding to improve training for diagnosis of genetic diseases and disorders, and for treatment and counseling.

The final part of the bill, one which may overlap with another bill sponsored by Senator Edward Kennedy (D – Mass.), would implement an oversight matrix for regulating genetic tests and pharmacogenomic tests, and would encourage the development of companion diagnostics by drug sponsors and by device companies.

Representative Kennedy also has added to the 2008 bill a tax credit for research expenses incurred in the development of a companion diagnostic test.

September 10th 2008 Posted to DNA Test & Personalized Medicine, News, US, Fall 2008

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With GINA Now Law, Aide Reaffirms Obama’s Commitment to Genomics Bill

July 11, 2008 By Matt Jones

WASHINGTON, DC (GenomeWeb News) – The US Senate could later this year take up a genomics bill introduced last year by presumptive Democratic presidential nominee Sen. Barack Obama, according to Obama’s health policy advisor, Dora Hughes.

Hughes told a Genetic Alliance meeting on Capitol Hill yesterday that Obama “remains committed” to seeing that the bill, the Genomics and Personalized Medicine Act of 2007 (S. 976), which would focus on genetic testing, is passed, although she could not yet specify when it would make it into committee because of conflicts with the Laboratory Test Improvements Act (S. 736), a bill sponsored by Sen. Edward Kennedy (D – Mass).

The Genomics and Personalized Medicine Act of 2007, designed to “secure the promise of personalized medicine” by expanding and accelerating genomics research and initiatives, was introduced in March of last year by Sen. Obama (D – Ill) and co-sponsored by Sen. Richard Burr (R – NC). Both the Obama bill and the Kennedy bill were referred to the Senate Committee on Health, Education, Labor, and Pensions in March 2007, where they have remained.

After the passage of the Genetic Information Nondiscrimination Act in May, Hughes explained, Obama and his staff aimed to get the genomics and personalized medicine bill moving once again. Hughes said that when Obama “first said he wanted to do a genomics bill, he [also] said, ‘but I don’t want it to go anywhere until GINA passes.’” Kennedy’s absence from the senate over the past month due to illness could have slowed the progress of both bills, Hughes said, dampening hopes that either one could make it to a committee markup meeting before the Senate’s August recess.

Hughes spoke at the Genetic Alliance’s “Genetics Day on the Hill,” which was punctuated by a victory talk from Representative Louise Slaughter (D – NY), who first introduced GINA into Congress 13 years ago. Referring to the many years it took to get GINA passed, Slaughter said, “we had no idea that we would run into such a maelstrom” of difficulty and opposition. “Every two years we would introduce it … and at every juncture we would get more co-sponsors than we needed to pass the legislation,” she explained.

But, she lamented, “the Chambers’ of Commerce didn’t like it, the drug companies didn’t like it … it was almost impossible to believe the interference we got.” The Genomics and Personalized Medicine bill has four main parts. It would create a Genomics and Personalized Medicine Interagency Working Group made up of Department of Health and Human Services institutes and agencies such as the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, as well as groups outside of HHS. The bill also calls for a National Biobanking Initiative that would create a database for the collection and integration of genomics data and environmental and clinical health information.

Another section of the legislation calls for funding to improve training for genetic disease and disorder diagnosis, treatment, and counseling. The fourth part of the bill, which Hughes said contains “all of the contentious issues” that will require work with Kennedy, would encourage development of companion diagnostics by drug sponsors and by device companies. This section also calls for the creation and implementation of a decision matrix “to improve the oversight and regulation of genetic tests, including pharmacogenomic and pharmacogenetic tests,” the bill states. The Obama and Kennedy bills differ in their proposed regulation of genetic tests, an issue that is “contentious for many stakeholder groups,” Hughes said. But, she added, “We’ve been trying to move forward in terms of not bogging down the bill with those politics.” She said that Senator Burr’s office has been focused on measures in the bill that offer the most benefit and can find broad bipartisan support.

Hughes admitted that in spite of these efforts, there is no guarantee that the bill will move to a vote this year. She added, however, that “if Senator Obama is in the White House next year then a lot of this we can do without a bill.”

September 10th 2008 Posted to DNA Test & Personalized Medicine, News, US, Fall 2008

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Francis Collins forthcoming book on Personalized Medicine

Leading geneticist to write book on staying well

Tue Sep 2, 1:13 PM ET

Dr. Francis Collins, arguably the nation’s leading geneticist and author of the best-selling “The Language of God,” is working on a book that promises “stunning new revelations about why we get sick; what it means to be healthy; how we can prevent disease” and medical treatment.

HarperCollins will release “Body Language: How Personalized Medicine Will Change Your Life” in Fall 2009, the publisher announced Tuesday. Dr. Collins will write about “medical dilemmas his own family has experienced, among stories of patients from across the country, in every age group,” according to HarperCollins.

“Modern genetic research has revealed that we all are born with glitches in our DNA, glitches which have implications both for potential future disease and for day-to-day choices while we are still “healthy.” How much should you learn about your own glitches? How much should doctors be able to learn? The answers are shifting daily. This is the book that will explain it for all of us.”

Collins, who helped lead the breakthrough unraveling of the human genetic code — and found common ground between the belief in God and science — resigned last summer as head of the Human Genome Project at the National Institutes of Health. Writing a book was one reason he cited for stepping down.

The geneticist helped translate the complexities of DNA into everyday vernacular. Collins led the Human Genome Project that, along with a competing private company, mapped the genetic code — or “the book of human life,” as he famously called it.

http://news.yahoo.com

September 03rd 2008 Posted to DNA Test & Personalized Medicine, News, US, Fall 2008

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Researchers Report Stem Cell Advance

Personal Genetics Education Project - Tools for teachers

Rep. Kennedy Revives Obama’s Personalized Medicine Bill for Next Congress; Adds Incentives

With GINA Now Law, Aide Reaffirms Obama’s Commitment to Genomics Bill

Francis Collins forthcoming book on Personalized Medicine

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