Journal
LANCET
Volume 363, Issue 9419, Pages 1432-1437Publisher
LANCET LTD
DOI: 10.1016/S0140-6736(04)16102-3
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Funding
- NCI NIH HHS [T32CA09126-25] Funding Source: Medline
- NHLBI NIH HHS [HL70738, HL70813, HL70143] Funding Source: Medline
- NINDS NIH HHS [NS37556] Funding Source: Medline
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Background End-organ repair by adult haemopoietic stem cells is under great scrutiny with investigators challenging the notion of these cells' plasticity. Some investigations of animals and short-term human bone marrow transplants suggest that bone marrow can repair brain. We looked for evidence of clinically relevant marrow-derived restorative neurogenesis: long-term, multilineage, neural engraftment that is not the result of cell-fusion events. Methods We examined autopsy brain specimens from three sex-mismatched female bone-marrow-transplantation patients, a female control, and a male control. We did immunohistochemistry, fluorescence in-situ hybridisation, and tissue analysis to look for multilineage, donor-derived neurogenesis. Findings Hippocampal cells containing a Y chromosome were present up to 6 years post-transplant in all three patients. Transgender neurons accounted for 1% of all neurons; there was no evidence of fusion events since only one X chromosome was present. Moreover, transgender astrocytes and microglia made up 1-2% of all glial cells. Interpretation Postnatal human neuropoiesis happens, and human haemopoietic cells can transdifferentiate into neurons, astrocytes, and microglia in a long-term setting without fusing. Transplantable human haemopoietic cells could serve as a therapeutic source for long-term regenerative neuropoiesis.
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