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Human skin cells turned to stem cells

The Baltimore Sun

Scientists in the U.S. and Japan have converted human skin cells into stem cells like the ones found in embryos, a breakthrough that could yield regenerative therapies without igniting the ethical debates that have embroiled the field for nearly a decade.

Yesterday's announcements raise the possibility that cells taken from sick patients could be reprogrammed and used to repair tissues damaged by heart disease, diabetes and other illnesses.

The technique, achieved earlier this year in mice, holds two potential advantages. Because cells would originate with a patient's own body, they wouldn't be likely to trigger rejection once they are transplanted back.

But scientists said they were just as enthusiastic that the method, if it clears technical hurdles ahead, could sidestep moral objections over techniques involving cloning, the use of donated eggs or the destruction of human embryos.

Such objections caused President Bush to restrict federal funding for embryonic stem cell research in 2001.

Religious conservatives have voiced objections since the field burgeoned in 1998.

"This does not eliminate that controversy, but I believe that it's the beginning of the end of the controversy," said Dr. James Thomson of the University of Wisconsin, one of two centers publishing results this week.

Richard Doerflinger, deputy director of anti-abortion activities for the U.S. Conference of Catholic Bishops, called the work "a very significant breakthrough in finding morally unproblematic alternatives to cloning."

"I think this is something that would be readily acceptable to Catholics," Doerflinger, a longtime opponent of embryonic stem cell research, told the Associated Press.

Separate teams in the two countries achieved similar results using the same technique. The Wisconsin scientists reprogrammed cells taken from an infant's foreskin, publishing their findings in the journal Science. The Japanese researchers, publishing in Cell, used skin cells from the face of a 36-year-old woman.

Thomson said he doubts that embryonic stem cell researchers would abandon their work for "direct reprogramming," the phrase applied to the new technology.

In fact, he said, it could be another year or so before scientists confirm that the reprogrammed cells are identical to embryonic stem cells -- which are prized because they can turn into every cell type in the human body. This property is called pluripotency.

Days-old embryos, called blastocysts, develop a pocket of stem cells that later develop into bone, heart, muscle, hair and everything else in the body.

In the recent studies, scientists reset the clock on development, turning mature cells back into stem cells much like those in embryos.

Scientists widely hailed the papers as important discoveries that could change the face of stem cell research.

"It furthers the notion that you can take a cell that isn't pluripotent and turn it into one that is," said Michael Shamblott, a stem cell researcher at the Johns Hopkins School of Medicine.

"It opens up the doors to people like myself wanting to make cell therapies."

Shamblott has been researching ways to harness stem cells to conquer diabetes, a disease caused by the destruction of pancreatic "islet" cells.

"The biggest drag on embryonic stem cell research in the past is that you could make an islet, but if you put it into a patient, he's going to reject it," Shamblott said.

The researchers used a retrovirus to deliver four genes that were known to transform an ordinary adult cell into a stem cell. It was the same technique used earlier to convert mouse skin cells into stem cells.

But scientists said a major hurdle will be ensuring that direct reprogramming doesn't trigger cancer -- a concern anytime a cell's DNA is altered. Most cancers are caused by the inappropriate activation of genes, said Hopkins' Shamblott.

Retroviruses are also known to produce tumors, which come about when cells divide without letup.

"This is an exciting advance, and it's likely to be very valuable," said Douglas A. Melton, co-director of the Harvard Stem Cell Institute, in a statement. But "we have to remember this is still using retroviruses, which are a real limitation."

"We have to get rid of the viruses," said Konrad Hochedlinger, another Harvard stem cell researcher who published the results of similar work with mouse cells last summer.

"They could activate oncogenes or be turned on inappropriately in mature cells and cause cancer." Oncogenes are cancer-causing genes.

Biologist Kevin Eggan, scientific director of the New York Stem Cell Foundation, called the advance "tremendously exciting." But he said "it remains to be determined whether reprogramming can be achieved without using cancer-causing genes."

Speaking at a news briefing yesterday, Thomson said that direct reprogramming might provide a rejection-free source of stem cells that is also free of moral debate. But he said it doesn't solve the problem of turning those cells into safe and effective therapies.

"The hard thing is understanding the disease you're trying to cure and putting those cells in the body in a way that actually corrects the disease and allows [the right] genes to flourish," Thomson said.

jonathan.bor@baltsun.com frank.roylance@baltsun.com

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