Bone marrow-derived cells that populate the adult mouse brain preserve their hematopoietic identity.
Cytogenesis in the adult brain can result from the recruitment of circulating precursors, but the proposal that some such cells transdifferentiate into neural elements is controversial. We have reinvestigated this issue by following the phenotypic fate of bone marrow cells expressing the green fluorescent protein transplanted into the systemic circulation of irradiated mice. Thousands of donor-derived cells were detected throughout brains of recipients killed 1-12 months after transplantation, but none displayed neuronal, macroglial, or endothelial characteristics, even after injury. Among those that crossed the endothelium of the cerebral cortex, >99.7% were identified as perivascular macrophages. Newly formed parenchymal microglia were found in significant numbers only in the cerebellum and at injury sites. Therefore, bone marrow does supply the mature brain with new specialized cells; however, mesenchymal precursors neither adopt neural phenotypes nor contribute to cerebral vascular remodeling. This continuous traffic of macrophages across the blood-brain barrier provides a vehicle to introduce therapeutic genes into the nervous system.
Vallières
Luc
L
Laboratoire d'Endocrinologie Moléculaire, Centre de Recherche du Centre Hospitalier de l'Université Laval, Université Laval, Québec, Québec, G1V 4G2, Canada. Luc.Vallieres@crchul.ulaval.ca
Sawchenko
Paul E
PE
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D001921:Brain / Q000166:cytology*; D001930:Brain Injuries / Q000473:pathology / Q000628:therapy; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019070:Cell Lineage; D002541:Cerebral Decortication; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006413:Hematopoietic System / Q000166:cytology*; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology / Q000473:pathology; D010641:Phenotype; D013995:Time
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins