Endothelial progenitor cells improve functional recovery in focal cerebral ischemia of rat by promoting angiogenesis via VEGF.

To investigate the role of venous infusion of endothelial progenitor cells (EPCs) in the reendothelialization of acute focal cerebral ischemia model in rats. And explore the mechanism of VEGF to promote angiogenesis of functional recovery in focal cerebral ischemia of rat. A model of middle cerebral artery occlusion (MCAo) was used to mimic ischemia following EPCs extraction from the same donor rats. EPCs were characterized by CD34, CD45 and CD133 expressions, and confirmed by uptake of fluorescently labeled Dil-ac-LDL and FITC-UEA-1 and flow cytometry analysis. EPCs were expanded in vitro and injected into the jugular vein of the same donor animals daily for 5 days after ischemia surgery. EPC-treated animals received approximately 1 × 106 cells, while control animals received PBS. Animals were evaluated the functional recovery, endothelial cell proliferation, vascular distribution, and VEGF levels. The EPC-treated group showed lower infarct volume and a significant recovery of neurological function. We also observed increased vascular distribution through bromodeoxyuridine (BrdU) staining and high plasma VEGF levels in the EPC-treated group compared to control groups. Our results provided direct evidence that auto-graft EPCs can improve neurological outcome and revascularization after ischemic stroke and indicated an important role of VEGF in this process. Our study suggested that EPCs may have potential therapeutic applications for the ischemic cerebrovascular disease.