Comparison of bone marrow stromal cells derived from stroke and normal rats for stroke treatment.

Abstract

We compared the effect of treatment of stroke with bone marrow stromal cells from stroke rats (Isch-BMSC) and normal rats (Nor-BMSC) on functional outcome. Isch-BMSCs and Nor-BMSCs were intravenously injected into rats 24 hours after middle cerebral artery occlusion. To test the mechanism of Isch-BMSC-enhanced neurorestoration, Isch-BMSC and Nor-BMSC cultures were used. Isch-BMSC significantly promoted functional outcome and enhanced angiogenesis, arterial density, and axonal regeneration compared with Nor-BMSC treatment animals. Isch-BMSCs exhibited increased Angiopoietin-1, Tie2, basic fibroblast growth factor, glial cell-derived neurotrophic factor, vascular endothelial growth factor, and Flk1 gene expression compared with Nor-BMSC. Using transwell coculture of BMSCs with brain-derived endothelial cells, Isch-BMSCs increased phosphorylated-Tie2 activity in brain-derived endothelial cells and enhanced brain-derived endothelial cells capillary tube formation compared with Nor-BMSCs. Inhibition of Tie2 gene expression in brain-derived endothelial cells using siRNA significantly attenuated BMSC-induced capillary tube formation. These data suggest that Isch-BMSCs are superior to Nor-BMSCs for the neurorestorative treatment of stroke, which may be mediated by the enhanced trophic factor and angiogenic characteristics of Isch-BMSCs.