In the heated ethical debates over embryonic stem cells, Parkinson's disease often figures large. Advocates hope that scientists can turn these cells into ones that produce dopamine, replacing those lost in the disease. Now, a new paper suggests that mouse embryonic stem cells can indeed accomplish this feat and lead to a partial recovery for animals with brain damage akin to Parkinson's. But some of the animals also developed deadly tumors.
For the new finding, a team led by Ole Isacson of Harvard Medical School in Boston took a surprisingly straightforward route: They simply injected untreated embryonic stem cells into the rats' brains. In previous experiments, Isacson and his colleagues had found that undifferentiated embryonic stem cells, when injected into animals, seemed eager to become neurons; the problem was they frequently grew out of control and formed tumorous growths. Suspecting that the differentiating cells were sending conflicting signals to each other that promoted tumors, the team decided to test whether diluting the cells would encourage development into neurons.
The team injected about 2000 mouse embryonic stem cells each into the brains of 25 rats who had previously had their dopamine-producing neurons damaged, which causes a characteristic tendency to move in circles. Six rats showed no evidence that the transplanted cells survived, and five died with tumors. But 14 rats had surviving mouse cells in their brains 4 months after surgery, the team reported in a report published online by the Proceedings of the National Academy of Sciences. All of these grafts contained at least some dopamine-producing neurons, and many of those neurons expressed a protein marker called AHD2, a marker typical of the specific kinds of neurons lost in Parkinson's disease. In the rats that received transplants, Parkinson-like symptoms improved by an average of 40% after 9 weeks.
"What this work shows is that you can easily get dopamine-producing neurons in the brain," even from undifferentiated embryonic stem cells, says developmental neurobiologist Ron McKay of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland. But both McKay and Isacson caution that the work does not mean doctors will soon be injecting human embryonic stem cells into Parkinson's patients. "This shows that it can be done," Isacson says. "But there are big obstacles to bring this to clinical fruition."