Abstract—Transplantation of bone marrow stromal cells(BMSCs) is a potential therapy for ischemic stroke, but poorenvironmental conditions in brain lesions, such asinsufficient nutrition and oxygen free radical toxicity, limitthe efficacy of stem cell therapy. Here, we hypothesized thatMCI-186, a free radical scavenger, would have protectiveeffects on transplantation of BMSCs in a rat ischemia model.In vitro, flow cytometry showed the apoptotic rates ofBMSCs after simulated ischemia–reperfusion (I/R) injurywas significantly decreased when treated with MCI-186(P< 0.01). In vivo, rat transient middle cerebral artery occlusion(MCAO) model was established. Two separate MCAOgroups were administered with either MCI-186 or phosphate-buffered solution (PBS) immediately after arteryocclusion. MCI-186 significantly up-regulated the secretionof brain-derived neurotrophic factor, vascular endothelialgrowth factor and superoxide dismutase in ischemic brain,while malondialdehyde decreased and neuronal apoptosiswas inhibited. Furthermore, another four MCAO groupswere administered with either PBS, MCI-186, BMSCs(2 106) or a combination of MCI-186 and BMSCs. Whencompared with BMSCs or MCI-186 monotherapy, combinationtherapy significantly improved functional restoration,decreased infarct volume, and increased the number ofengrafted-BMSCs and neurons in ischemic brain. The numberof engrafted-BMSCs and neurons was significantly correlatedwith functional outcomes. This study suggests thatMCI-186 may improve the environment of the injured brain,enhance the survival of engrafted-BMSCs and neurotizationin ischemic brain and produce protective effects on BMSCstransplantation. Crown Copyright 2012 IBRO. Publishedby Elsevier Ltd. All rights reserved.
Key words: Bone marrow stromal cells (BMSCs), Ischemicstroke, MCI-186, Growth factor, Oxygen free-radical, Neurons.
