Published online 30 November 2007 | Nature | doi:10.1038/news.2007.219

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A simpler recipe for human stem cells

Adult skin cells turned to pluripotent stem cells without a cancer-causing agent.

Cell reprogramming taken one step further.National Institutes of Health

Shinya Yamanaka of Kyoto University in Japan has followed the announcement last week of his startling success in turning human skin cells to embryo-like stem cells, by reporting that he has done the same without the cancer-causing agent used in his original recipe.

The work brings scientists perhaps one step closer to the goal of being to use patient-matched stem cells for therapy.

Yamanaka first demonstrated his method for ‘reprogramming’ cells in mice. Last year he showed that he could produce pluripotent cells — cells that can turn into any of the roughly 220 cell types in the body — by using retroviruses to carry four genes into mouse skin cells1. The four genes reprogrammed the mouse cells to a state similar to those in the early embryo. He named the cells induced pluripotent stem (iPS) cells. But one of those genes, c-myc, is known as an oncogene, which can cause cancer. When Yamanaka produced live mice from embryos injected with these pluripotent cells, 20% of them developed tumours.

When last week Yamanaka reported similar success using human cells2, the announcement was tempered by the fact that such cells, made using c-myc, would pose a danger to transplant recipients.

In the further work published by Nature Biotechnology today3, Yamanaka shows that he can make both human and mouse iPS cells with just three factors, without using c-myc.

Last week James Thomson of the University of Wisconsin in Madison and his colleagues also reported a success with four factors that did not include c-myc4. But Thomson's result needs further work. He created his pluripotent cells using fetal not adult cells, whereas medical applications will require that adult cells be used. And Thomson's method has not tested in mice, he says. "We've tested these cells in mice and we know they are safe," says Yamanaka.

Before any pluripotent cells will be ready for use in human transplant therapies, however, much more work needs to be done. To reduce risks to recipients, the introduced genes may have to be eliminated altogether, perhaps by simulating their function with a small molecule, or the genes will have to be introduced in a way that does not require viral vectors. 

  • References

    1. Takahashi, K. & Yamanaka, S. Cell. 126, 663-676 (2006). | Article | PubMed | ISI | ChemPort |
    2. Takahashi, K. et al. Cell 131, 861-872 doi:10.1016/j.cell.2007.11.019 (2007). | PubMed |
    3. Nakagawa M. et al, Nature Biotechnol. doi: 10.1038/nbt1374 (2007).
    4. Yu, J. et al. Science doi: 10.1126/science.1151526 (2007).
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