A team of Japanese researchers has changed epithelial cells from the livers and stomachs of adult mice into pluripotent cells that resemble embryonic stem cells, according to a paper in this week's Science.

In 2006, the Kyoto University team, led by Shinya Yamanaka, used retroviruses to transfect adult mouse fibroblasts and embryonic cells with four transcription factors, reprogramming them into pluripotent cells. Last year they used the technique to reprogram human fibroblasts into pluripotent stem cells, setting off a whirlwind of research attention focused on reprogramming fibroblasts into stem cells that might grow into specific tissues and organs for transplant.

But the current study suggests that stem cells generated from adult epithelial cells rather than adult fibroblasts may provide better raw material for patient-specific tissues and organs.

Lorenz Studer, of the Memorial Sloan-Kettering Cancer Center, said that the Yamanaka study may shift the stem cell research community's focus on fibroblasts. "Everyone wanted to use fibroblasts," he told The Scientist. "But people will now go back and ask, 'Is this the right population to make patient-specific cells?'"

Yamanaka and his collaborators used retroviral vectors to introduce four transcription factors - Oct 3/4, Sox2. Klf4, and c-Myc - into mouse hepatic and gastric cells, and the resulting cells grew into several different cell types.

The authors compared epithelial cell-derived to fibroblast-derived pluripotent cells and found that the former were more similar to embryonic stem cells and were less likely to cause tumors in chimeric mice grown from the cells. This last feature appeared to result from the fact that pluripotent cells generated from liver or stomach cells needed only one to four specific insertion sites for each gene transfected via retrovirus, whereas reprogramming fibroblasts requires many more so-called integration sites. This increased retroviral integration can activate oncogenes and increase cancer risk in reprogrammed fibroblasts.

"If you can make [stem] cells with fewer integration sites, that would be the cell of choice to do pre-clinical trials in animals," Studer, who was not involved with the Yamanaka study, said. That's why "this paper is important for future reprogramming studies," he added.

Editor's Note (posted Feb. 14, 2007): A link to the Science paper has been added.