Oct. 13, 2008
Researchers at Harvard announced October 12 that they have produced flexible, embryonic-like iPS cells (induced pluripotent stem cells) by adding only two genes and "sprinkling" a helping chemical onto cells. The iPS cell method, first developed by Dr. Shinya Yamanaka of Japan in 2006, involves adding four genes (via viruses) to "reprogram" normal cells so that they behave like embryonic stem cells, but without the use of embryos, eggs, or cloning. The first human iPS cells were announced in November 2007 by Yamanaka and by Dr. James Thomson. The race has been on to simplify the reprogramming process, using fewer genes and safer viruses, or no viruses at all. Over the last ten months, numerous groups have reported improved methods and use of fewer genes, including a recent published report using safer viruses that deliver the genes and then disappear. Yamanaka has just published results showing that iPS reprogramming can be done completely without viruses for the gene additions. Meanwhile other researchers have been attempting to use simple chemicals or proteins to accomplish reprogramming, rather than using any DNA. Previous work has used soluble proteins with three genes, and a combined genetic and chemical approach. Now Doug Melton's group, building on their previous work with making mouse iPS cells, has demonstrated that human iPS cells can be produced by adding only two key genes along with a simple chemical. They eliminated the need for potential cancer causing genes, adding only the two genes Oct-4 and Sox-2, both master regulators of stem cell gene expression. The chemical additive, valproic acid, acts on the DNA-protein complex in the nucleus of cells to open its structure, making reprogramming easier. While the method they used for this study still involves viruses to deliver the genes, Melton noted that "This study demonstrates there's a possibility that instead of using genes and viruses to reprogram cells, one can use chemicals," and "These results support the possibility of reprogramming through purely chemical means." With the rapidly-increasing number of researchers moving into the cell reprogramming field and away from use of embryos and cloning, it shouldn't be long before the possibility is realized.