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Targeting gene-modified hematopoietic cells to the central nervous system: Use of green fluorescent protein uncovers microglial engraftment

Item Type:Article
Title:Targeting gene-modified hematopoietic cells to the central nervous system: Use of green fluorescent protein uncovers microglial engraftment
Creators Name:Priller, J., Fluegel, A., Wehner, T., Boentert, M., Haas, C.A., Prinz, M., Fernandez-Klett, F., Prass, K., Bechmann, I., de Boer, B.A., Frotscher, M., Kreutzberg, G.W., Persons, D.A. and Dirnagl, U.
Abstract:Gene therapy in the central nervous system (CNS) is hindered by the presence of the blood-brain barrier, which restricts access of serum constituents and peripheral cells to the brain parenchyma. Expression of exogenously administered genes in the CNS has been achieved in vivo using highly invasive routes, or ex vivo relying on the direct implantation of genetically modified cells into the brain. Here we provide evidence for a novel, noninvasive approach for targeting potential therapeutic factors to the CNS. Genetically-modified hematopoietic cells enter the CNS and differentiate into microglia after bone-marrow transplantation. Up to a quarter of the regional microglial population is donor-derived by four months after transplantation. Microglial engraftment is enhanced by neuropathology, and gene-modified myeloid cells are specifically attracted to the sites of neuronal damage. Thus, microglia may serve as vehicles for gene delivery to the nervous system.
Keywords:Blood-Brain Barrier, Bone Marrow Cells, Bone Marrow Transplantation, Brain Ischemia, Cell Differentiation, Gene Targeting, Gene Therapy, Genetic Vectors, Green Fluorescent Proteins, Luminescent Proteins, Microglia, Recombinant Proteins, Retroviridae, Animals, Mice
Source:Nature Medicine
ISSN:1078-8956
Publisher:Nature Publishing Group
Volume:7
Number:12
Page Range:1356-1361
Date:1 December 2001
Official Publication:https://doi.org/10.1038/nm1201-1356
PubMed:View item in PubMed

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