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The Journal of Neuroscience, June 15, 2003, 23(12):5197-5207
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Bone Marrow-Derived Cells that Populate the Adult Mouse Brain Preserve Their Hematopoietic Identity
Luc Vallières1 andPaul E. Sawchenko2 1Laboratoire d'Endocrinologie Moléculaire, Centre de Recherche du Centre Hospitalier de l'Université Laval, Université Laval, Québec, Québec, G1V 4G2, Canada, and 2Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies, La Jolla, California 92037
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.
Key words: postnatal neurogenesis; gliogenesis; vasculogenesis; bone marrow stem cells; lineage restriction; transdifferentiation; GFP mice
Received Jan. 13, 2003; revised Apr. 7, 2003; accepted Apr. 14, 2003.
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