Therapeutic Benefit of Intravenous Administration of Bone Marrow Stromal Cells After Cerebral Ischemia in Rats

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Abstract
Background and Purpose —We tested the hypothesis that intravenous infusion of bone marrow derived–marrow stromal cells (MSCs) enter the brain and reduce neurological functional deficits after stroke in rats. Methods —Rats (n=32) were subjected to 2 hours of middle cerebral artery occlusion (MCAO). Test groups consisted of MCAO alone (group 1, n=6); intravenous infusion of 1×10 6 MSCs at 24 hours after MCAO (group 2, n=6); or infusion of 3×10 6 MSCs (group 3, n=7). Rats in groups 1 to 3 were euthanized at 14 days after MCAO. Group 4 consisted of MCAO alone (n=6) and group 5, intravenous infusion of 3×10 6 MSCs at 7 days after MCAO (n=7). Rats in groups 4 and 5 were euthanized at 35 days after MCAO. For cellular identification, MSCs were prelabeled with bromodeoxyuridine. Behavioral tests (rotarod, adhesive-removal, and modified Neurological Severity Score [NSS]) were performed before and at 1, 7, 14, 21, 28, and 35 days after MCAO. Immunohistochemistry was used to identify MSCs or cells derived from MSCs in brain and other organs. Results —Significant recovery of somatosensory behavior and Neurological Severity Score ( P 6 MSCs at 1 day or 7 days compared with control animals. MSCs survive and are localized to the ipsilateral ischemic hemisphere, and a few cells express protein marker phenotypic neural cells. Conclusions —MSCs delivered to ischemic brain tissue through an intravenous route provide therapeutic benefit after stroke. MSCs may provide a powerful autoplastic therapy for stroke.