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Transplanted Stem Cells Migrate to Brain, Differentiate Into Neurons

http://www.medscape.com/viewarticle/448187

Jan 20, 2003
By Karla Gale
Reuters Health
NEW YORK

Adult bone marrow stem cells can cross the blood-brain barrier and differentiate into neurons, according to results of an autopsy study reported in the Proceedings of the National Academy of Sciences early edition.

"There are indeed cells in the blood that can enter the human brain and become neurons there," Dr. Eva Mezey, of the National Institute of Neurological Disorders and Stroke in Bethesda, told Reuters Health.

Dr. Mezey's group examined postmortem brain samples from four female patients who had received bone marrow transplants from male donors. The one patient with Omenn's syndrome underwent transplantation when she was 9 months old and survived a further 10 months. The other three patients had lymphoma or leukemia and died within about 2 months after transplantation.

The researchers labeled sections from the neocortex, striatum, hippocampus and cerebellum with antibodies against NeuN, a neuron-specific nuclear protein, with Kv2.1, a neuron-specific potassium channel, and with a radiolabeled Y chromosome probe.

All four patients exhibited Y-positive cells, most of which were non-neuronal. However, labeled neurons were found, primarily in the hippocampus and the neocortex. In the patient who had survived the longest after undergoing transplant, Dr. Mezey's team observed clusters of Y-positive cells, suggesting clonal expansion.

Based on findings from the two patients for whom they counted the number of labeled neurons, the authors estimate that out of every 2000 to 4000 neurons, one might derive from the bone marrow.

Dr. Mezey remarked that it is possible that if the patients had lived longer, more stem cells would have migrated into the brain, resulting in more neurogenesis.

In order for clinically relevant numbers of neurons to be developed from stem cells, Dr. Mezey noted that researchers will need to increase the number that migrate into the brain. "Cytokines are known to increase the number of circulating stem cells, but the factors that direct migration and differentiation of stem cells in the brain still have to be found," she added.

Proc Natl Acad Sci 2003. www.pnas.org/cgi/coi/10.1073/pnas.0336479100
 

© 2003 Reuters Ltd