Protective effects of MCI-186 on transplantation of bone marrow stromal cells in rat ischemic stroke model.

Transplantation of bone marrow stromal cells (BMSCs) is a potential therapy for ischemic stroke, but poor environmental conditions in brain lesions, such as insufficient nutrition and oxygen free radical toxicity, limit the efficacy of stem cell therapy. Here, we hypothesized that MCI-186, a free radical scavenger, would have protective effects on transplantation of BMSCs in a rat ischemia model. In vitro, flow cytometry showed the apoptotic rates of BMSCs after simulated ischemia-reperfusion (I/R) injury was significantly decreased when treated with MCI-186 (P<0.01). In vivo, rat transient middle cerebral artery occlusion (MCAO) model was established. Two separate MCAO groups were administered with either MCI-186 or phosphate-buffered solution (PBS) immediately after artery occlusion. MCI-186 significantly up-regulated the secretion of brain-derived neurotrophic factor, vascular endothelial growth factor and superoxide dismutase in ischemic brain, while malondialdehyde decreased and neuronal apoptosis was inhibited. Furthermore, another four MCAO groups were administered with either PBS, MCI-186, BMSCs (2×10(6)) or a combination of MCI-186 and BMSCs. When compared with BMSCs or MCI-186 monotherapy, combination therapy significantly improved functional restoration, decreased infarct volume, and increased the number of engrafted-BMSCs and neurons in ischemic brain. The number of engrafted-BMSCs and neurons was significantly correlated with functional outcomes. This study suggests that MCI-186 may improve the environment of the injured brain, enhance the survival of engrafted-BMSCs and neurotization in ischemic brain and produce protective effects on BMSCs transplantation.