Background: Acute myocardial infarction (MI) leads to an irreversible loss of proper cardiac function. Application of\nstem cell therapy is an attractive option for MI treatment. Adipose tissue has proven to serve as a rich source of stem\ncells (ADSCs). Taking into account the different morphogenesis, anatomy, and physiology of adipose tissue, we\nhypothesized that ADSCs from different adipose tissue depots may exert a diverse multipotency and cardiogenic\npotential.\nMethods: The omental, pericardial, and epicardial adipose tissue samples were obtained from organ donors and\npatients undergoing heart transplantation at our institution. Human foreskin fibroblasts were used as the control group.\nIsolated ADSCs were analyzed for adipogenic and osteogenic differentiation capacity and proliferation potential. The\nimmunophenotype and constitutive gene expression of alkaline phosphatase (ALP), GATA4, Nanog, and OCT4 were\nanalyzed. DNA methylation inhibitor 5-azacytidine was exposed to the cells to stimulate the cardiogenesis. Finally,\nreprogramming towards cardiomyocytes was initiated with exogenous overexpression of seven transcription factors\n(ESRRG, GATA4, MEF2C, MESP1, MYOCD, TBX5, ZFPM2) previously applied successfully for fibroblast transdifferentiation\ntoward cardiomyocytes. Expression of cardiac troponin T (cTNT) and alpha-actinin (Actn2) was analyzed 3 weeks after\ninitiation of the cardiac differentiation.\nResults: The multipotent properties of isolated plastic adherent cells were confirmed with expression of CD29, CD44,\nCD90, and CD105, as well as successful differentiation toward adipocytes and osteocytes; with the highest osteogenic\nand adipogenic potential for the epicardial and omental ADSCs, respectively. Epicardial ADSCs demonstrated a lower\ndoubling time as compared with the pericardium and omentum-derived cells. Furthermore, epicardial ADSCs revealed\nhigher constitutive expression of ALP and GATA4. Increased Actn2 and cTNT expression was observed after the\ntransduction of seven reprogramming factors, with the highest expression in the epicardial ADSCs, as compared with\nthe other ADSC subtypes and fibroblasts.\nConclusions: Human epicardial ADSCs revealed a higher cardiomyogenic potential as compared with the pericardial\nand omental ADSC subtypes as well as the fibroblast counterparts. Epicardial ADSCs may thus serve as the valuable\nsubject for further studies on more effective methods of adult stem cell differentiation toward cardiomyocytes.
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