Published online 1 March 2009 | 458, 19 (2009) | doi:10.1038/458019a

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Virus-free pluripotency for human cells

Stem-cell advance could bring tailored treatments closer.

Researchers are close to making safer stem cells.K. Woltjen et al.

For the first time, specialized human cells have been transformed into a state similar to that seen in embryonic stem cells, without using viruses. The advance edges stem-cell biologists closer to clearing a barrier to using reprogrammed cells for therapies and drug screening.

"The field has been waiting for these papers," says Marie Csete, chief scientific officer at the California Institute for Regenerative Medicine in San Francisco.

Embryonic stem cells are pluripotent — capable of generating all the body's specialized cell types — and creating tailor-made cell lines might allow scientists to better study human diseases and test possible treatments. That looked difficult until 2006, when Shinya Yamanaka and his colleagues at Kyoto University in Japan reported that they had reprogrammed mouse skin cells into an embryonic-like state by infecting them with a virus containing four genetic factors. Yamanaka called the reprogrammed cells induced pluripotent stem (iPS) cells.

Since then, scientists have used various viral vectors to reprogram human cells with the 'Yamanaka factors', and have used non-viral methods to reprogram mouse cells. No one had been able to reprogram human cells without using viruses — which integrate unpredictably into the genome — until now.

Stem-cell researchers led by Andreas Nagy, of the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in Toronto, Canada, and Keisuke Kaji, of the University of Edinburgh, UK, inserted genes encoding Yamanaka's factors into a piece of DNA, or cassette, that also contained a jumping gene known as piggyBAC. The teams showed that this cassette could be inserted into the DNA of mouse and human skin cells and could reprogram them back to an embryonic-like state (K. Kaji et al. Nature doi:10.1038/nature07864; 2009, K. Woltjen et al. Nature doi:10.1038/nature07863; 2009).

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The teams then used an enzyme called transposase to remove the cassette from the mouse cells. But some scientists say that until the cassette is removed from human cells, the technique is not a major advance over viral methods.

Nagy, however, is confident that he will be able to use transposase to remove the cassette from human cells. He is currently trying to use his method to reprogram cat and dog cells. 

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