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Reprogrammed stem cells have genetic mutations, studies show

March 03, 2011|By Eryn Brown, Los Angeles Times

Two studies released Wednesday by the journal Nature show that work remains before so-called induced pluripotent stem (iPS) cells are ready for use in laboratory studies or clinical therapies.

iPS cells are body cells that are programmed to unwind back into an embryonic state.  Like embryonic stem cells, they have potential to develop into any other type of cell in the body.

But they don't reprogram perfectly, researchers are showing.  About a month ago, a team at the Salk Institute showed that iPS cells hold on to "memory" of their past identity.  They reported changes in the cells' epigenomes, chemical markers attached to DNA that regulate the way genes dial on and off.

The papers released this week show that the processes through which iPS cells are reprogrammed also can create significant abnormalities in the DNA itself -- places where the cells' basic genetic blueprint is altered.  

Such reprogramming errors could affect the cells' usefulness in the future, the authors wrote.

"These mutations could alter the properties of the stem cells, affecting their applications in studying degenerative conditions and screening for drugs to treat diseases," said coauthor Dr. Andras Nagy of the Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Toronto, in a press release.
Nagy said that the discovery of the mutations also had "important implications" for the use of iPS cells in medical therapies.

Researcher Kun Zhang of the University of San Diego, a coauthor on the other paper, referred to abnormalities as "permanent genome scars."

The teams suggested that iPS cells should undergo careful genetic screening before they're used -- by scientists in the lab or by doctors at the bedside.

Scientists have held out great hope for iPS cells.  Because they aren't generated from embryos, they don't present the same ethical concerns as ES cells. Also, because they can be generated from a patient's own cells, it is thought that iPS cells won't pose the risk of rejection that tissues created out of embryonic stem cells do.   

In a separate study researchers at Stanford University reported a new method to prevent immune system rejection in human embryonic stem cells transplanted in mice.  Their results, which suggest there may be options that avoid the side effects of traditional immunosuppressant drugs, were published Thursday in the journal Cell Stem Cell.

RELATED: The Times interviewed iPS cell pioneer Shinya Yamanaka last year. RELATED: The Times reports on epigenetic changes in iPS cells.

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