Transplanted Bone Marrow Generates New Neurons in Human Brains

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 100; no. 3; pp. 1364 - 1369
• Main Authors: Mezey, Éva, Key, Sharon, Vogelsang, Georgia, Szalayova, Ildiko, Lange, G. David, Crain, Barbara
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 04.02.2003; National Acad Sciences; The National Academy of Sciences
• Subjects: Adult; Biological Sciences; Bone marrow; Bone marrow cells; Bone Marrow Cells - cytology; Bone Marrow Transplantation; Brain; Brain - metabolism; Brain - physiology; Cell Differentiation; Cell Division; Child; Endothelial cells; Female; Hepatocytes; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Infant; Male; Microscopy, Confocal; Microscopy, Fluorescence; Neural stem cells; Neurons; Neurons - metabolism; Neurons - pathology; Pyramidal cells; Stem cells; Transplants & implants
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0336479100

Adult bone marrow stem cells seem to differentiate into muscle, skin, liver, lung, and neuronal cells in rodents and have been shown to regenerate myocardium, hepatocytes, and skin and gastrointestinal epithelium in humans. Because we have demonstrated previously that transplanted bone marrow cells can enter the brain of mice and differentiate into neurons there, we decided to examine postmortem brain samples from females who had received bone marrow transplants from male donors. The underlying diseases of the patients were lymphocytic leukemia and genetic deficiency of the immune system, and they survived between 1 and 9 months after transplant. We used a combination of immunocytochemistry (utilizing neuron-specific antibodies) and fluorescent in situ hybridization histochemistry to search for Y chromosome-positive cells. In all four patients studied we found cells containing Y chromosomes in several brain regions. Most of them were nonneuronal (endothelial cells and cells in the white matter), but neurons were certainly labeled, especially in the hippocampus and cerebral cortex. The youngest patient (2 years old), who also lived the longest time after transplantation, had the greatest number of donor-derived neurons (7 in 10,000). The distribution of the labeled cells was not homogeneous. There were clusters of Y-positive cells, suggesting that single progenitor cells underwent clonal expansion and differentiation. We conclude that adult human bone marrow cells can enter the brain and generate neurons just as rodent cells do. Perhaps this phenomenon could be exploited to prevent the development or progression of neurodegenerative diseases or to repair tissue damaged by infarction or trauma.