December 16, 2010

Using Chemicals to Reprogram iPS Cells



     Induced pluripotent stem (iPS) cells

The field of induced pluripotent stem (iPS) cells continues to move rapidly. It was only 2006 when Yamanaka published the first paper showing that a normal cell, such as a skin cell, could be reprogrammed to behave like an embryonic stem cell, by adding four genes through the use of viruses. In 2007, Yamanaka's lab and Thomson's lab independently showed that the technique could work with human cells. Since that time there have been numerous reports of different tissues, different species, and variations on the reprogramming (here is a brief review.) One goal has been eliminating use of DNA as a tool for the reprogramming, eventually using only simple chemicals.

Recently a Scripps lab has come close to using only chemicals for reprogramming normal cells to iPS cells. The report, published in the journal Cell Stem Cell, describes the use of a few drug-like chemicals to replace all but one (Oct-4) of the added genes. A future goal is to replace Oct-4, a master regulator of pluripotency, in the chemical cocktail.

Senior author Sheng Ding says:

"That would be the last step toward achieving the Holy Grail. Our latest discovery brings us one step closer to this dream. We are working toward creating drugs that are totally chemically defined, where we know every single component and precisely what it does, without causing genetic damage."

Because iPS cells can be made without the use of embryos, eggs or cloning, the technique provides an ethical route to pluripotent (embryonic-like) stem cells. Using only a chemical mixture would eliminate one other ethical problem–some of the tools used (some genes, viruses, and cell lines used) are derived from human tissue. This leaves some of the tools as ethically-tainted, even if the technique itself is not problematic.

Still, there remains a problem with any pluripotent stem cell–their propensity to grow, leading to tumors. Meanwhile, adult stem cells are already treating thousands of patients now.

Contact: 
David Prentice
Source: FRC Blog
Publish Date: December 15, 2010