Effect of glucagon-like peptide-1 on differentiation of adipose derived mesenchymal stem cells into cardiomyocytes

Abstract

Aim: Mesenchymal stem cells can easily differentiate into cardiomyocytes in vitro conditions using various protocols. However, the agents used in these protocols have been reported to have some adverse effects on cell viability. Azacitidine is used to differentiate mesenchymal stem cells into cardiac muscle cells. The aim of the present study was to investigate the effects of Exenatide a GLP-1 receptor agonist, on differentiation and viability of human adipose tissue derived stem cells into cardiomyocytes. Materials and Methods: The effects of Azacytidine and Exenatide on cell viability and proliferation of human adipose tissue derived stem cells were analyzed with cytotoxicity assay. For differentiation procedure, of human adipose tissue derived stem cells were incubated with Azacytidine and Exenatide through four weeks. The morphological alterations of human adipose tissue derived stem cells were monitored and the expressions of cardiomyogenic differentiation markers (cTnI, GATA4 ve MYH7) were evaluated immunohistochemically. Also, cardiac troponin I (cTnI) levels in the cultures were measured using enzyme-linked immunosorbent assay. Results were evaluated by one way analysis of variance (ANOVA) and post-hoc test. Results: Treatment of the human adipose tissue derived stem cells with Azacytidine significantly decreased cell viability (54.4%) compared to control whereas treatment of cells with Azacytidine + Exenatide prevented cell death in a dose-dependent manner. Cells treated with Azacytidine and Exenatide showed significant morphological alterations consistent with cardiyomyogenic differentiation, and increase in expression cardiomyogenic markers. cTnI levels were found significantly higher in cultures treated separately and together with Azacytidine and Exenatide compared to control. Conclusion: Overall, these findings suggested that GLP-1 receptor agonist Exenatide may have beneficial effects on cardiomyogenic differention of human adipose tissue derived stem cells by reducing cell damage caused by Azacytidine

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