The Other Stem Cells
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The process that Svendsen and other researchers are using—harvesting a differentiated adult cell, returning it to a pluripotent state in the lab, then sending it down the path to specialization—has achieved remarkable results. But other scientists have been exploring whether a shortcut might be possible. What if the transformation could happen in the body? In a study published in October 2008, Melton showed that it was possible to take an exocrine cell in the pancreas of a live mouse and turn it into an insulin-producing beta cell without first going back to an undifferentiated iPS state. He added only three transcription factors, and the process took just three days instead of the three weeks needed to produce an iPS cell. In people with diabetes, beta cells don’t function well, but Melton and his team were able to use the new beta cells to improve the glucose state of diabetic mice.
The potential for that approach remains to be established. And indeed all the research involving iPS cells is still at an early stage. No one yet knows what’s actually going on in cells when they’re reprogrammed, and cancer is still a very real problem, with most rodents that get iPS cells developing the disease. What’s more, iPS cells are not perfect models for every disease. “They are good for developmental disorders such as SMA,” says Svendsen, but scientists don’t yet know if they will work as well with diseases that develop over many decades. “Alzheimer’s disease doesn’t strike most people until they’re at least in their seventies, so you might have to leave the cells in the dish for 70 years until they show any symptoms,” he says. “That’s a little longer than my NIH grant.”
Moreover, research to be published soon might show small but perhaps crucial differences between induced pluripotent stem cells and the embryonic variety that could affect potential applications. Yet such issues have done little to dampen scientists’ enthusiasm. “Certain boundaries that we thought were there really aren’t,” says Hochedlinger. “And it may be possible to overcome problems we thought could never be solved.”
