Treatment of stroke in rat with intracarotid administration of marrow stromal cells

Objective: To measure the therapeutic efficacy for the treatment of stroke with intra-arterial administration of bone marrow stromal cells (MSC). Back ground: MSC have characteristics of stem and progenitor cells. The hypothes is that MSC injected into the internal carotid artery after stroke enter in to ischemic brain and improve neurologic recovery was tested. Methods: Twen ty-five adult Wistar rats were subjected to transient (2-hour) middle cereb ral artery occlusion alone (n = 9), or treated with intracarotid arterial i njection of 200 muL phosphate-buffered saline (n = 8) or 2 x 10(6) MSC in 2 00 muL phosphate-buffered saline (n = 8) 1 day after ischemia. MSC were har vested and isolated from additional adult rats and then cultured and labele d with bromodeoxyuridine. Rats were subjected to neurologic functional test s (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 MSG. Results: Bromodeoxyuridine-reactive cells (similar to 21% of 2 x 106 i njected MSG) distributed throughout the territory of the middle cerebral ar tery by 14 days after ischemia. Some bromodeoxyuridine-reactive cells expre ssed proteins characteristic of astrocytes and neurons. Rats with intra-art erial transplantation of MSC exhibited improvement on the adhesive-removal test (p < 0.05) and the modified neurologic severity scores (p < 0.05) at 1 4 days compared with controls. Conclusions: MSC injected intra-arterially a re localized and directed to the territory of the middle cerebral artery, a nd these cells foster functional improvement after cerebral ischemia.