Abstract 12545: Autologous Induced Mesenchymal Stem Cells-derived Exosomes Exhibit Enhanced Protection Of Cardiomyocytes From Injuries

Abstract

Introduction: Mesenchymal stem cells (MSC)-derived exosomes containing small non-coding RNAs (sncRNAs) showed protection of the myocardium from injury, infection, and disease. Recently, we have generated a safe and non-viral method of generating induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) with high replicative, autologous, cardioprotecive potentials, originally derived from human urinary epithelial cells. Hypothesis: We hypothesize that exosomes from iMSC possess a superior cardioprotective, and regenerative characteristics compared to the exosomes from adult umbilical cord MSCs (hereafter referred as MSCs) for the treatment of ischemic cardiomyopathy (ICM). Methods & Results: Exosomes isolated from serum-free conditioned media obtained from iMSCs and MSCs were characterized using Zetasizer, which showed that exosomes from iMSCs had smaller particle size than the MSCs (Fig. A). Exosomal tetraspanin proteins (CD9, CD63 and CD81) were identified by Western blotting. Cardioprotective properties of exosomes were evaluated using functional iPSC-derived cardiomyocytes (iCMCs), which were treated with 50 μg of exosomes 1 hr before subjecting them to either 24 hrs of Ang II treatment (10 μM) or 6 hrs of 1% hypoxia and 24 hrs of reoxygenation. The exosomes from iMSCs elicited a superior cardioprotective characteristic studied through qRT-PCR expression of survival genes and measurement of mitochondrial membrane potentials (JC1 dye), intracellular reactive oxygen species (CM-H2DCFDA), and in situ cell death by apoptosis (Fig. B) when compared to the exosomes from MSCs. Furthermore, the expressions of injury-associated sncRNAs such as SNORD32a, SNORD33, and SNORD35a were identified in both exosomes. Conclusions: In comparison with the exosomes of available MSCs, exosomes from iMSCs showed an enhanced protection of cardiomyocytes from injuries and can be a valuable cell-free source for the treatment of ICM.