By Rob Waters
Sept. 25 (Bloomberg) -- Ordinary cells from mice can be manipulated to acquire the power of embryonic stem cells in a way that's less likely to trigger cancer than the current method, Harvard University researchers said today in the journal Science.
The report adds momentum to efforts to create new kinds of stem cells that may one day be used as therapies for such hard- to-treat conditions as spinal-cord injuries, diabetes and Parkinson's disease.
The Harvard advance builds on the achievement of Shinya Yamanaka of Kyoto University, who electrified scientists two years ago with a method for inserting four genes into the skin cells of mice or people to make what he calls ``induced pluripotent stem cells.'' These multipurpose cells behave like those from embryos with the potential to replace or regenerate body tissue. Since that accomplishment, researchers have been searching for ways to make the technique safer.
``It's very exciting,'' said John Dimos, senior scientist at iZumi Bio Inc., a closely held company in Mountain View, California, formed last year to develop therapies using the new pluripotent cells. ``This paper confirms what we've seen recently -- that there are a number of ways to produce embryonic stem cell-like cells.''
The Harvard researchers, led by Konrad Hochedlinger, used a type of virus called an adenovirus, commonly employed in gene therapy, to ferry certain genes into ordinary cells and endow them with the power to act like embryonic stem cells. In contrast, Yamanaka used a type of virus called a retrovirus. Retroviruses lodge permanently in the DNA of cells they enter, which increases the risk of cancer. Adenoviruses don't.
Tails and Livers
The Harvard researchers took cells from the tail and livers of mice and exposed them to adenoviruses loaded with the same genes Yamanaka had used, said Hochedlinger, a scientist at the Cancer Center and Center for Regenerative Medicine at Massachusetts General Hospital in Boston. His laboratory is now trying the same thing in humans and he thinks it's likely they'll succeed, he said yesterday in a telephone interview.
After three to four weeks, colonies of cells that resembled embryonic stem cells began to appear and grow larger over time. When researchers injected the material into early mouse embryos removed from their mothers, then inserted the embryos into other females to be carried to term, the resulting pups had pluripotent stem cells in organs throughout their bodies. When these mice grew to adulthood and mated, they gave birth to offspring whose genes incorporated the DNA of the pluripotent stem cells, Hochedlinger said.
`Gold Standard'
``They can pass their chromosomes to the next generation,'' he said. ``That's the gold standard of a pluripotent stem cell.''
Hochedlinger and his colleagues performed other tests to be certain the stem cells they created acted like embryonic stem cells and to look for remnants of adenovirus in the cells.
Unlike retroviruses, adenoviruses are slowly diluted out of cells as they replicate, with each new daughter containing half the amount of its parent, Hochedlinger said. When his team analyzed the colonies six weeks after they'd formed, they found no sign of viral remnants.
Still, said iZumi Bio's Dimos, it would be preferable to find other methods to mimic the way Yamanaka's four genes reprogram cells and turn on their ability to morph into other cells.
Detecting risks
``They still used a virus and there is still a chance that it integrates into the genome,'' he said. ``They didn't see it, but absence of evidence is not the same as evidence of absence.''
Dimos's company was formed to use pluripotent cells to develop and test drugs and to create treatments. Researchers and companies hoping to use such therapies will need to prove the cells don't harbor any viral fragments. They'll also need to show that the genes used to transform the cells don't trigger cancer or cause other unwanted effects.
The best and safest way to accomplish this is not yet clear. Many scientists believe that chemicals may be found that will trigger the same changes as the genes and viruses do.
``It makes sense to pursue different approaches and then go with the one that is most efficient and gives rise to the safest stem cells,'' said Hochedlinger.
To contact the reporter on this story: Rob Waters in San Francisco at rwaters5@bloomberg.net.
Last Updated: September 25, 2008 14:00 EDT
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