Image: Science/Dr. EVA MEZEY, NINDS
In recent years research into stem cells has demonstrated their remarkable ability to become different types of cellseven after they have already started down a particular developmental path. Scientists are especially interested in harnessing this versatility to repair damaged spinal cords and brains. Studies have shown that neural stem cells transplanted into the brain migrate throughout that organ and apparently develop into the kinds of cells that exist in the brain. And additional work has revealed that even bone marrow stem cells can become neuronlike--at least in culture. Now two new studies, described today in the journal Science, demonstrate for the first time that bone marrow cells can perform this feat in living animals. The research suggests that bone marrow could provide a readily available source of neurons to replace those lost or damaged as a result of central nervous system injury, or neurodegenerative diseases like Parkinson's.
In the first study, Eva Mezey of the National Institute of Neurological Disorders and Stroke (NINDS) and her colleagues transplanted bone marrow cells from normal male mice into newborn female mice that could not produce immune system cells. Four months after the transplant, the brains of the female mice were examined. To their surprise, the researchers found in several regions of the brain neuronlike cells clearly descended from the transplanted cells. (The Y-chromosome in the male-derived cells acted as a natural marker.) On reaching the brain, it appears, the bone marrow cells transformed into neurons (above; green spot indicates the Y-chromosome).
In the second study, Helen Blau and her colleagues at Stanford University took bone marrow that expressed a marker called green fluorescent protein from adult mice and injected it into other adults that had been irradiated to eliminate their bone marrow. There, too, the transplanted bone marrow cells made their way into various regions of the brain. Moreover, some of these cells sprouted long fibers and produced a protein that signifies activity, suggesting that they were functioning like native neurons.
That bone marrow from adult mice yielded neuronal cells suggests that patients in need of replacement neurons could be treated with their own cells, which would not be rejected by the immune system, Blau says. Researchers still have fundamental questions to address before bone marrow cells can be tested in humans, however. For example, which population of bone marrow cells develops into neurons remains to be determined. And whether the marrow-derived neurons function entirely normally is not yet clear. But these new results will likely spur further research. "These are extraordinarily important studies," NINDS director Gerald D. Fischbach remarks, "carefully done, with clear implications for brain disorders and for basic developmental biology."