Detection of bone marrow-derived cells expressing a neural phenotype in the human brain.
Animal studies suggest that adult bone marrow cells have the potential to migrate into the brain and generate new neural cells. Because data on this physiologic repair mechanism in humans are lacking, we investigated bone marrow engraftment into the brain of bone marrow recipients after sex-mismatched transplantation. Brain sections of seven allogeneic female bone marrow recipients were examined. The Y-chromosome, which served as a natural marker of donor bone marrow-derived cells after male-to-female transplantation, was identified by in situ hybridization. The neural phenotype of Y-chromosome-positive cells was determined using neural nuclear protein (NeuN) immunohistochemistry. Y-chromosome-positive cells expressing NeuN were found within the first 3 months after transplantation in both the cerebrum and the cerebellum at a frequency of 0.003% to 0.013% of all neurons. These cells were observed only in patients with cerebral lymphocytic infiltration and graft-versus-host disease. Our data suggest that adult bone marrow cells are capable of generating cells that express the neural marker NeuN early after transplantation. Cells with this specific phenotype may contribute to tissue repair in brain regions remote from neurogenic zones.
Sostak
Petra
P
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany. Petra.Sostak@med.uni-muenchen.de
Theil
Diethilde
D
Stepp
Herbert
H
Roeber
Sigrun
S
Kretzschmar
Hans A
HA
Straube
Andreas
A
D000328:Adult; D034961:Antigens, Nuclear / Q000096:biosynthesis / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D041322:Chromosomes, Human, Y; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006085:Graft Survival / Q000502:physiology*; D006086:Graft vs Host Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009416:Nerve Regeneration / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D013687:Telencephalon / Q000166:cytology / Q000378:metabolism; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods
D034961:Antigens, Nuclear; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; C506808:neuronal nuclear antigen NeuN, human