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From the Departments of Neurology (Drs. Li, Chen, Wang, and Chopp) and Biostatistics and Research Epidemiology (Dr. Lu), Henry Ford Health Sciences Center, Detroit; and the Department of Physics (Dr. Chopp), Oakland University, Rochester, MI.
Address correspondence and reprint requests to Dr. Michael Chopp, Department of Neurology (E&R3056), Henry Ford Health Sciences Center, 2799 West Grand Boulevard, Detroit, MI 48202; e-mail: chopp{at}neuro.hfh.edu
OBJECTIVE: To measure the therapeutic efficacy for the treatment of stroke with intra-arterial administration of bone marrow stromal cells (MSC).
BACKGROUND: MSC have characteristics of stem and progenitor cells. The hypothesis that MSC injected into the internal carotid artery after stroke enter into ischemic brain and improve neurologic recovery was tested.
METHODS: Twenty-five adult Wistar rats were subjected to transient (2-hour) middle cerebral artery occlusion alone (n = 9), or treated with intracarotid arterial injection of 200 µL phosphate-buffered saline (n = 8) or 2 x 106 MSC in 200 µL phosphate-buffered saline (n = 8) 1 day after ischemia. MSC were harvested and isolated from additional adult rats and then cultured and labeled with bromodeoxyuridine. Rats were subjected to neurologic functional tests (adhesive-removal, modified neurologic severity scores) before and at 1, 7, and 14 days after middle cerebral artery occlusion. Immunohistochemistry was used to identify cell-specific proteins of bromodeoxyuridine-reactive MSC.
RESULTS: Bromodeoxyuridine-reactive cells (
21% of 2 x 106 injected MSC) distributed throughout the territory of the middle cerebral artery by 14 days after ischemia. Some bromodeoxyuridine-reactive cells expressed proteins characteristic of astrocytes and neurons. Rats with intra-arterial transplantation of MSC exhibited improvement on the adhesive-removal test (p < 0.05) and the modified neurologic severity scores (p < 0.05) at 14 days compared with controls.
CONCLUSIONS: MSC injected intra-arterially are localized and directed to the territory of the middle cerebral artery, and these cells foster functional improvement after cerebral ischemia.
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