Scripps Research Institute researchers have found a molecule that will convert adult differentiated adult muscle cells into undifferentiated stem cells.

La Jolla, CA. December 22, 2003—A group of researchers from The Scripps Research Institute has identified a small synthetic molecule that can induce a cell to undergo dedifferentiation—to move backwards developmentally from its current state to form its own precursor cell.

This compound, named reversine, causes cells which are normally programmed to form muscles to undergo reverse differentiation—retreat along their differentiation pathway and turn into precursor cells. These precursor cells are multipotent; that is, they have the potential to become different cell types. Thus, reversine represents a potentially useful tool for generating unlimited supply of such precursors, which subsequently can be converted to other cell types, such as bone or cartilage.

"This [type of approach] has the potential to make stem cell research more practical," says Sheng Ding, Ph.D. "This will allow you to derive stem-like cells from your own mature cells, avoiding the technical and ethical issues associated with embryonic stem cells."

Ding, who is an assistant professor in the chemistry department at Scripps Research conducted the study—to be published in an upcoming issue of the Journal of the American Chemical Society—with Peter G. Schultz, Ph.D., who is a professor of chemistry and Scripps Family Chair of Scripps Research's Skaggs Institute of Chemical Biology, and their colleagues.

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Stem cell therapy would be most effective if you could use your own stem cells, since using one's own cells would avoid potential complications from immune rejection of foreign cells. However, in general it has proven very difficult to isolate and propagate stem cells from adults. Embryonic stem cells (ESCs) offer an alternative, but face both practical and ethical hurdles associated with the source of cells as well as methods for controlling the differentiation of ESCs. A third approach is to use one's own specialized cells and dedifferentiate them.

This is excellent news. The ability to use one's own cells as a starting point for making stem cells to treat one's own illnesses would avoid the immune rejection problems that make stem cells from non-self sources so problematic.

This molecule reversine is not the only molecule discovered recently that is useful for controlling the differentiation state of cells. Currently human embryonic stem cells have to be grown on top of mouse cells in order to prevent the stem cells from differentiating. The mouse cells release compounds that prevent the cells from differentiating. The problem with doing this is that the human cells may get contaminated in some way that could make them risky to be used in human therapy. Well, Ali Brivanlou of Rockefeller University has identified a compound extracted from sea snails that prevents stem cell differentiation.

Ali Brivanlou of Rockefeller University in New York says that he and his colleagues may have found a partial solution to these problems. Brivanlou treated ES cells with a chemical, nicknamed BIO, from a sea snail.

BIO stopped ES cells turning into specialized adult cells, Brivanlou and his colleagues found. BIO works by activating a set of protein signals - called the Wnt pathway - in the ES cells1.

Slowly but surely more tools and techniques are being developed to make stem cell growth and differentiation and dedifferentiation controllable.