Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats

Background and Purpose-We tested the hypothesis that intravenous infusion o f bone marrow derived-marrow stromal cells (MSCs) enter the brain and reduc e neurological functional deficits after stroke in rats. Methods-Rats (n=32) were subjected to 2 hours of middle cerebral artery occ lusion (MCAO). Test groups consisted of MCAO alone (group 1, n=6); intraven ous infusion of 1 x 10(6) MSCs at 24 hours after MCAO (group 2, n=6); or in fusion of 3x10(6) MSCs (group 3, n=7). Rats in groups 1 to 3 were euthanize d at 14 days after MCAO. Group 4 consisted of MCAO alone (n=6) and group 5, intravenous infusion of 3x10(6) MSCs at 7 days after MCAO (n=7). Rats in g roups 4 and 5 were euthanized at 35 days after MCAO. For cellular identific ation, MSCs were prelabeled with bromodeoxyuridine. Behavioral tests (rotar od, adhesive-removal, and modified Neurological Severity Score [NSS]) were performed before and at 1, 7, 14, 21, 28, and 35 days after MCAO. Immunohis tochemistry was used to identify MSCs or cells derived from MSCs in brain a nd other organs. Results-Significant recovery of somatosensory behavior and Neurological Sev erity Score (P<0.05) were found in animals infused with 3x106 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 marke r 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.