Abstract 20070: Hypoxic Reprogramming of Exosomal Mirnas by Ets Transcription Factors in Human CD34+ Stem Cells Promotes Ischemic Tissue Repair

Introduction: In a first study of its kind, we have demonstrated a novel mechanism that therapeutic human CD34+ stem cells secrete membrane bound nano-sized vesicles called exosomes (Exo) into their paracrine secretion. Our preliminary data suggests that cell-free Exo mimic the angiogenic and therapeutic activity of CD34+ cells and carry several proangiogenic miRNAs, such as miR-126 that affects their function. Hypothesis: We hypothesized that the regenerative efficacy of the cell-free CD34Exo can be improved by hypoxic pre-conditioning, modulating its pro-angiogenic miRNA content. Methods and Results: Exosomes from human peripheral blood-derived CD34+ cells cultured under hypoxia (H-Exo) were significantly more proliferative, anti-apoptotic and angiogenic in vitro, as compared to exosomes from cells under normoxia (N-Exo). Treatment with H-Exo significantly improved perfusion (ratio: 0.93±0.05 v 0.77±0.02), increased capillary density (1.6±0.2 v 1.1±0.1/HPF) and prevented ischemic limb amputation (0% v 3...