Bone marrow transdifferentiation in brain after transplantation: a retrospective study.
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.


RESULTS
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.


CONCLUSIONS
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.
Cogle
Christopher R
CR
Program in Stem Cell Biology and Regenerative Medicine, University of Florida Shands Cancer Center, Gainesville, FL 32610, USA.
Yachnis
Anthony T
AT
Laywell
Eric D
ED
Zander
Dani S
DS
Wingard
John R
JR
Steindler
Dennis A
DA
Scott
Edward W
EW
D000328:Adult; D001253:Astrocytes / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation; D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology; D012189:Retrospective Studies; D018183:Transplantation Chimera