While research on human embryonic stem cells gets most of the press, scientists are also investigating the potential therapeutic uses of adult stem cells. Although less controversial, this research faces other difficulties. Adult stem cells are extremely difficult to isolate and multiply in the lab.
Now, as reported in the May 6 issue of Cell, researchers led by Rudolf Jaenisch of the Whitehead Institute have discovered a mechanism that might enable scientists to multiply adult stem cells quickly and efficiently.
"These findings provide us with a new way of looking at adult stem cells and for possibly exploiting their therapeutic potential," says Jaenisch, who also is a professor of biology at MIT.
This research focuses on a gene called Oct4, a molecule that is known to be active in the early embryonic stage of an organism. Oct4's primary function is to keep an embryo in an immature state. It acts as a gatekeeper, preventing the cells in the embryo from differentiating into tissue-specific cells. While Oct4 is operating, all the cells in the embryo remain identical, but when Oct4 shuts off, the cells begin growing into, say, heart or liver tissue.
Konrad Hochedlinger, a postdoctoral researcher in Jaenisch's lab, was experimenting with the Oct4 gene, curious to see what would happen in laboratory mice when the gene was reactivated in adult tissue in which it had long been dormant. Hochedlinger found that when he switched the gene on, the mice immediately formed tumors in the gut and in the skin where the gene was active. When he switched the gene off, the tumors subsided, demonstrating that the process is reversible.
Discovering that simply flipping a single gene on and off had such an immediate effect on a tumor was unexpected, even though Oct4 is known to be active in certain forms of testicular and ovarian cancer. Still, the most provocative finding was that "Oct4 causes tumors by preventing adult stem cells in these tissues from differentiating," says Hochedlinger. In other words, with Oct4 active, the stem cells could replicate themselves indefinitely, but could not produce mature tissue.