06 June 2007

Adult Fibroblasts Reprogrammed to Become Embryonic Stem Cells?

This research appears to confirm earlier research published last year, that differentiated cells from adult mice can be induced to revert to the pluripotency of an embryonic stem cell.
Now, scientists at Whitehead Institute have demonstrated that embryonic stem cells can be created without eggs. By genetically manipulating mature skin cells taken from a mouse, the scientists have transformed these cells back into a pluripotent state, one that appears identical to an embryonic stem cell in every way. No eggs were used, and no embryos destroyed.

“These reprogrammed cells, by all criteria that we can apply, are indistinguishable from embryonic stem cells,” says Whitehead Member and MIT professor of biology Rudolf Jaenisch, senior author of the paper that will appear online June 6 in Nature.

What’s more, these reprogrammed skin cells can give rise to live mice, contributing to every kind of tissue type, and can even be transmitted via germ cells (sperm or eggs) to succeeding generations. “Germline transmission is the final and definitive proof that these cells can do anything a traditionally derived embryonic stem cell can do,” adds Jaenisch.

Two additional papers report similar findings. The first, by Shinya Yamanaka of Kyoto University, will be published in the same issue of Nature. The second, from Konrad Hochedlinger, formerly of the Jaenisch lab and now at Center for Regenerative Medicine at Massachusetts General Hospital and Harvard Stem Cell Institute, will appear in the inaugural issue of the journal Cell Stem Cells. Additionally, another paper in Nature from Kevin Eggan, also of the Harvard Stem Cell Institute and a former member of the Jaenisch lab, describes using mouse zygotes, rather than eggs, for somatic cell nuclear transfer.

Jaenisch cautions that “all these results are preliminary and proof of principle. It will be a while before we know what can and can’t be done in humans. Human embryonic stem cells remain the gold standard for pluripotent cells, and it is a necessity to continue studying embryonic stem cells through traditional means.”

In August 2006, a team of researchers at Kyoto University led by Yamanaka reported a landmark discovery that by activating four genes in a mouse skin cell, they could reprogram that cell into a pluripotent state resembling an embryonic stem cell. However, the resulting cells were limited when compared with real embryonic stem cells, and the Kyoto team was unable to generate live mice from these cells.

A team of researchers decided to replicate this experiment, while refining certain technical aspects.

The approach taken by the researchers is intriguing, and so far appears to show that these reprogrammed mature fibroblasts are functionally and genetically indistinguishable from pluripotent ESCs.

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