1 December 2000

Stem Cells Develop Into Neurons In Living Animals

by Kate Melville

For years, researchers studying stem cells have been intrigued by the possibility that these cells might be used to treat brain diseases. Recent studies have suggested that neural stem cells transplanted into the brain can migrate throughout the brain and develop into other types of cells. Now, two new studies show that bone marrow cells transplanted into mice can migrate into the brain and develop into cells that appear to be neurons. The studies suggest that bone marrow may be a readily available source of neural cells with potential for treating such neurological disorders as Parkinson's disease and traumatic brain injury.

While previous research has shown that bone marrow cells can develop into neuron-like cells in culture, the new studies are the first to show that this process can also happen in living animals. The two studies reached the same conclusion despite many differences in how the studies were performed. The results are reported in the December 1, 2000, issue of Science.

"These are extraordinarily important studies, carefully done, with clear implications for brain disorders and for basic developmental biology," says Gerald D. Fischbach, M.D., director of the National Institute of Neurological Disorders and Stroke (NINDS).

In the first study,(1) NINDS investigator éva Mezey, M.D., Ph.D., and colleagues injected bone marrow cells from normal male mice into newborn female mice that had no white blood cells of their own. Using marrow from male mice allowed the researchers to use the Y chromosomes in the transplanted cells as a marker to distinguish them from native cells. At different time intervals, the researchers examined cells from the brains of seven mice that had received the transplants and compared them to littermates that had not received the transplants. By 4 months after the transplants, they found a significant number of neuronal cells in several brain regions, including the cortex, the hypothalamus, and the striatum, that were descendants of the transplanted cells. This suggests that stem cells from elsewhere in the body can enter the brain and differentiate into neuronal cells, says Dr. Mezey.

In the second study,(2) Helen Blau, Ph.D., and colleagues from Stanford University injected bone marrow from adult mice that express a marker called green fluorescent protein (GFP) into adult mice that had been irradiated to eliminate their bone marrow. They found that bone marrow-derived cells migrated into several regions of the brain, including the olfactory bulb, the cortex, the hippocampus, and the cerebellum. Some of the marrow-derived neuronal cells also grew long fibers and produced a protein that indicates cell activity. These results suggest that the marrow-derived neurons not only entered the brain but also responded to their environment and began to function like the native ones.

These studies suggest that bone marrow, which is an easily available source of cells, could be used as a source of neurons to replace those damaged or lost in neurological disorders, the researchers say. It might also be possible to genetically engineer the cells in ways that would help them survive or work in beneficial ways. The fact that even bone marrow from adult mice generated neuronal cells shows an unexpected amount of flexibility in older cells and suggests that patients with brain disorders could be treated with their own cells, says Dr. Blau. Bone marrow cells taken from a patient's own body would not be rejected by the body's immune system.

While the results are very promising, researchers need to answer many remaining questions before marrow-derived neural cell therapies can be tested in humans. A key question is what growth factors and other signals prompt the bone marrow cells to develop into specific types of neurons. If researchers can describe how the normal process of cell differentiation works, they may be able to reproduce it in patients with disorders such as brain injury or Parkinson's disease where neurons are not normally replaced. Researchers might also be able to discover factors that help cells enter the brain or connect with other cells. "We need much more data, but I think it's a pretty encouraging start," says Dr. Mezey.

Since the studies used whole bone marrow, it is important to determine which population of bone marrow cells develop into neurons, the researchers say. Other questions for future studies include whether marrow-derived neurons function like normal neurons and if they can make appropriate connections with other cells. The findings in Science should speed the pace of research to answer these and other important questions, the researchers say. However, they believe it will be several more years before the results reported in these studies will lead to effective therapies.