Abstract 177: Exosomal Micrornas From Ischemic Cerebral Endothelial Cells and Neural Stem Cells Regulate Coupling of Neurogenesis and Angiogenesis

Introduction: Molecular mechanisms underlying coupling of angiogenesis and neurogenesis remain unknown. We tested the hypothesis that exosomes mediate coupling of stroke-induced angiogenesis and neurogenesis by transferring exosomal cargo miRNAs between ischemic cerebral endothelial cells (CECs) and neural stem cells (NSCs). Methods and Results: Cell-type specific exosomes were purified from conditional media of cultured CECs and NSCs harvested from non-ischemic and ischemic rats, respectively. Exosome markers and size distribution were verified with Western blot and transmission electron microscopy, respectively. Using an advanced Cre-Loxp system, we found CEC-exosomes carrying Cre recombinase were taken up by recipient NSCs to induce genome recombination. We then tested if exosomal miRNAs mediated cell-to-cell interplay. First, using miRNA array, we identified that miR-146a and miR-125a were the most upregulated miRNAs in ischemic CECs-exosomes. Incubation of non-ischemic NSCs with ischemic CECs-exosome...