Researchers Report Stem Cell Advance

by Jeffrey Perkel ,  Washingtonpost.com | 2008-09-25

Researchers report that they have sidestepped a major technical hurdle in the generation of pluripotent stem cells from adult cells.

A team of Boston scientists developed a way to generate induced pluripotent stem cells (iPS) -- which are functionally similar to embryonic stem cells, but which can be produced from adult cells, rather than via the creation or destruction of an embryo -- more safely than ever.

Should the findings, which involved mouse cells, be repeated with humans, they could pave the way for using iPS to delve into the biology of a wide range of genetic diseases. Longer term, they could lead to patient-specific stem-cell therapies.

"I think it's a really important, landmark study," said Kevin Eggan, an assistant professor of Stem Cell and Regenerative Biology and an assistant investigator of the Stowers Medical Institute at Harvard University. He was not involved in the study.

The results were published in the Sept. 25 online edition of Science.

Shinya Yamanaka, of Kyoto University, Japan, first demonstrated in 2006 that adult mouse cells -- for instance, skin cells -- could be reprogrammed into something akin to an embryonic stem cell by the introduction of four specific genes. According to the lead author of this latest study, Matthias Stadtfeld, that "was like a gigantic, essentially quantum leap for biology." The following year, Yamanaka and James Thomson, of the University of Wisconsin, Madison, demonstrated the same approach could create human iPS cells.

Normally, the four genes -- all of which can induce cancer if left unchecked -- are delivered using retroviruses, which integrate their viral DNA into the cells' chromosomes; the worry is that these random insertions will introduce mutations into the cells that would alter their behavior, thus minimizing the cells' potential usefulness as research tools. Should these cells ever be used to generate tissues that were transplanted into human patients, researchers fear they could inadvertently lead to cancer.

Konrad Hochedlinger, of Massachusetts General Hospital and the Harvard Stem Cell Institute, his postdoctoral fellow Stadtfeld, and their colleagues circumvented this problem by delivering the genes using adenoviruses instead, which do not insert their viral DNA into a cell's chromosomes. iPS cells generated by this new approach appear indistinguishable from other iPS cells, carry some of the molecular hallmarks of embryonic stem cells, and can form multiple cell types when transplanted into mice (that is, they are pluripotent).



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