Journal
EXPERIMENTAL NEUROLOGY
Volume 195, Issue 1, Pages 16-26Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2005.03.018
Keywords
experimental autoimmune encephalomyelitis; human bone marrow stromal cells; oligodendrocyte progenitor cell; brain-derived neurotrophic factor; mice
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Funding
- NINDS NIH HHS [R01 NS45041, P01 NS042345, R01 NS045041, P01 NS42345] Funding Source: Medline
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We investigated the treatment of remitting-relapsing experimental autoimmune encephalomyclitis (EAE) in mice with human bone marrow stromal cells (hBMSCs). hBMSCs were injected intravenously into EAE mice upon onset of paresis. Neurological functional tests were scored daily by grading clinical signs (score 0-5). lmmunohistochemistry was performed to measure the transplanted hBMSCs, cell proliferation (bromodeoxyuridine, BrdU), oligodendrocyte progenitor cells (NG2), oligodendrocytes (RIP), and brain-derived neurotrophic factor (BDNF). The maximum clinical score and the average clinical scores were significantly decreased in the hBMSC-transplanted mice compared to the phosphate-buffered-saline-treated EAE controls, indicating a significant improvement in function. Demyelination significantly decreased, and BrdU(+) and BDNF+ cells significantly increased in the hBMSC-treated mice compared to controls. Some BrdU+ cells were colocalized with NG2(+) and RIP+ immunostaining. hBMSCs also significantly reduced the numbers of vessels containing inflammatory cell infiltration. These data indicate that hBMSC treatment improved functional recovery after EAE in mice, possibly, via reducing inflammatory infiltrates and demyelination areas, stimulating oligodendrogenesis, and by elevating BDNF expression. (c) 2005 Elsevier Inc. All rights reserved.
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