Therapeutic Effect of Human Umbilical Cord Multipotent Mesenchymal Stromal Cells in a Rat Model of Stroke

Background. Human umbilical cord multipotent mescnchymal stromal cells (UC-MSC) have recently been identified as ideal candidate stern cells for cell-based therapy. The present study was designed to evaluate therapeutic potentials of intracerebral administration of UC-MSC in a rat model of stroke. Methods. Rats were subjected to 2-hr middle cerebral artery occlusion and received 2 x 10(5) UC-MSC or phosphate-buffered saline as a control. Neurologic function evaluation was conducted weekly after transplantation. Brain injury volume and in vivo differentiation of transplanted UC-MSC were detected 2 or 5 weeks after the UC-MSC treatment. In addition, vascular density, vascular endothelial growth factor, and basic Fibroblast growth factor expression in ipsilateral hemisphere after treatment and in vitro angiogenic potential of UC-MSC were assessed. Results. The transplanted UC-MSC survived for at least 5 weeks in rat brain. Compared with the phosphate-buffered saline control, the UC-MSC treatment significantly reduced injury volume and neurologic functional deficits of rats after stroke. In ischemic brain, UC-MSC widely incorporated into cerebral vasculature and a subset of them was capable of differentiating into endothelial cells. Furthermore, the UC-MSC treatment Substantially increased vascular density and vascular endothelial growth factor and basic fibroblast growth factor expression in ipsilateral hemisphere of stroke. In vitro induction and tube formation assay further confirmed their angiogenic properties. Conclusions. UC-MSC transplantation could accelerate neurologic functional recovery of rats after stroke, which may be mediated by their ability to promote angiogenesis.