Japanese researchers who reprogrammed pluripotency into adult human skin cells say they have improved the technique, according to a paper published online today (Nov. 30) in Nature Biotechnology.

Shinya Yamanaka of Kyoto University and his colleagues originally used four transcription factors to induce pluripotency in mouse embryonic and adult fibroblast cells, and most recently, adult human skin cells. But the process caused tumors in a significant percentage of the chimeric mice generated from the cells - a problem the researchers attributed to one of the four genes, c-Myc, which induces proliferation.

In the current study, the researchers showed that pluripotent cells can be made from both mouse and human adult cells without introducing the c-Myc gene, by transducing just the other three. It's not that Myc isn't needed in the process, the authors noted in the paper; rather, they suggest that the other three genes may be spurring endogenous Myc activity. None of the 26 chimeras made from cells generated without c-Myc developed tumors within 100 days, compared to six out of 36 chimeras made from cells using all four genes.

James Thomson's group at the University of Wisconsin, Madison, also reported reprogramming human cells last week, using a set of four transcription factors that did not include c-Myc. So far, though, they have used their approach in neonatal cells, but not adult cells.

The Yamanaka group's study "suggests that tumour formation was indeed due to abnormal cMyc expression rather than some general problem of the reprogramming method," Robin Lovell-Badge of the MRC National Institute for Medical Research in London, wrote in an Email to The Scientist. "However, they did not look thoroughly for tumours and screened relatively few animals, so more work is needed on this."

So far, too, efficiency with this triple-gene method is much lower than with the original four genes; half of the experiments without c-Myc did not produce pluripotent cells at all, while experiments using the four genes almost always yielded pluripotent colonies. "Does this mean that it now only works with a rare cell type?" Lovell-Badge wrote. "As always, many more questions are posed than answered."