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Working Mice Spun From Skin Cells

• July 25, 2009 • 12:25 AM

In demonstrating that embryonic stem cells may not be the experimental bottleneck as they are often seen, researchers have created live mice from mouse skin.

Embryonic cells are no longer the only cells that can produce live offspring. Two separate Chinese research teams reported this week that they have been able to reprogram skin tissue cells of mice into an embryonic-like state.

The cells, called induced pluripotent stem cells, were first produced in 2006 by a Japanese research team from Kyoto University. They have long been theorized to have pluripotent abilities (the potential to differentiate into any cell type in the body except placenta) that could be used in future degenerative and genetic disease treatment. But until now scientists have been unable to use the cells to produce live offspring and, as a result, show they are as versatile as embryonic stem cells.

The two studies, one published online in the journal Nature, the other in Cell Stem Cell, followed similar protocols.

To create the iPS cells, the teams used viral vectors to introduce four particular stem cell genes into mice fibroblast cells (the cells that create connective tissues in the body). From there the teams embedded the iPS cells into “tetraploid” embryos, which normally only develop external supportive tissues like placenta on their own, and not an actual offspring. Afterwards, the now complete embryos were implanted into surrogate mothers, and the scientists waited to see if viable infant mice developed.

According to their Cell Stem Cell article, it took the research team led by Lan Kang of the Chinese Academy of Medical Sciences and Peking Union Medical College some 187 iPS cell embryos to produce a single live mouse offspring. But skin cells harvested from pups that died shortly after cesarean section deliveries did produce more efficient iPS cells that were more likely to create viable embryos.

The researchers who published in Nature were able to produce 22 live offspring from 624 embryos, but observed relatively high death and physical abnormality rates in the infant mice. They were, however, able to mate 12 of the surviving offspring, and found that none of the second generation of mice had any abnormalities or tumors. While the sample size is still relatively small, this later result is important because some scientists fear the use of viral vectors in iPS cell production increase rates of cancer because the virus leaves its own DNA in the cell when inserting the stem cell genes.

While the results of these studies suggest a new avenue for stem cell research that side steps the ethical debate surrounding embryonic stem cell harvesting, both sets of authors are quick to downplay the results as evidence that iPS cell research could soon be applied to humans.

“Although these findings are an important proof of principle,” said the Kang group in their study, “It would be premature to make claims based on them about whether iPS cells in general are functionally equivalent to normal embryonic stem cells as we have only identified one iPSC line that possesses this capacity (in mice) and the process is still very inefficient.”

“It may be more complicated than what the current model will accommodate.”

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Julia Griffin
Julia Griffin is a master's candidate in environmental science and management at the University of California, Santa Barbara. A fellow at the Miller-McCune Center in 2009, before that she worked as a film researcher for John-Michel Cousteau's Ocean Future Society and a producer/writer in CNN's Science and Technology Unit. She has a degree in marine biology from Duke University, and hopes to pursue a career in science and environmental journalism.

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