Administration of ex vivo-expanded bone marrow-derived endothelial progenitor cells attenuates focal cerebral ischemia-reperfusion injury in rats

OBJECTIVE: This study aimed to examine early effects of ex vivo-expanded bone marrow-derived endothelial progenitor cells (EPCs) on focal cerebral ischemia-reperfusion injury. METHODS: EPCs were obtained from mononuclear cells of autologous bone marrow of a rat. After culture on fibronectin-coated dishes for 10 to 14 days, 2.5 X 10(5) cells of EPCs were administered transarterially after 90 minute occlusion of the middle cerebral artery. RESULTS: Administration of EPCs significantly reduced both the infarct volume and the scores of neurological deficits at 24 and 48 hours. EPCs administered 2 hours after insult did not reduce infarct volume, but attenuated neurological deficits at 24 hours. Administration of EPCs significantly reduced the number of myeloperoxidase-immunoreactive cells in the ischemic lesion at 24 hours and increased regional cortical blood flow at 48 hours. EPCs were observed in the ischemic hemisphere and around the endothelial layer of the pial arteries. Most of them expressed endothelial nitric oxide synthase. CONCLUSION: Administration of ex vivo-expanded bone marrow-derived EPCs reduced infarct volume and neurological deficits in acute focal brain ischemia-reperfusion injury caused, at least in part, by attenuation of endothelial dysfunction.