Exosomes secreted by cardiosphere-derived cells induce differentiation of adipose mesenchymal stem cells into cardiomyocyte-like cells

Introduction: Exosome-based therapy has emerged as a novel approach to treat degenerative heart diseases that destroy cardiomyocytes. Exosomal research evidence suggests these extracellular nanovesicles play a role in repairing damaged cardiac tissue.Purpose: This study aimed to investigate the effect of exosomes secreted by cardiosphere-derived cells (CDCs) on the differentiation of adipose-derived mesenchymal stem cells (AdMSCs) into cardiomyocytes in vitro.Methods/Material: Exosomes were isolated from CDCs of Balb/c mouse embryos after separation by ultracentrifugation and characterized by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) and Western Blotting. AdMSCs of adult mice in the third passage, were divided into three groups, i.e., untreated AdMSCs (control group), AdMSCs treated with CDC-derived exosomes (CDC-Exos group) and AdMSCs treated with a combination of ۵-azacitidine, ascorbic acid and Transforming growth factorβ-۱ (Aza+AA+TGFβ۱ group) after flow cytometry. Treated AdMSCs were evaluated regarding morphology and expression of cardiac genes (including Pdgfrα, Gata۴, Nkx۲-۵, Mef۲c, Tnnt۲, and Myh۷) by qRT-PCR on days ۰, ۳ and ۷ after treatment.Results: Morphological examination of AdMSCs showed transformation towards myotubes from the third day in both CDC-Exos and Aza+AA+TGFβ۱ groups with an increased amount of myotubes on the seventh day compared to the control group. Moreover, qRT-PCR results in both CDC-Exos and Aza+AA+TGFβ۱ groups revealed significant expression of cardiac genes on the seventh day after treatment compared to the control group (P ≤ ۰.۰۵).Discussion: The results of this study suggest that CDC-Exos could be considered as a novel regenerative tool for differentiation of AdMSCs into cardiomyocytes and repair of damaged myocardium.

کلیدواژه ها:

Cardiosphere-derived cell ، Exosome ، Differentiation ، Adipose mesenchymal stem cell ، Cardiomyocyte