Effect of a dianthin G analogue in the differentiation of rat bone marrow mesenchymal stem cells into cardiomyocytes.

Abstract

Loss of cardiomyocytes due to myocardial infarction results in ventricular remodeling which includes non-contractile scar formation, which can lead to heart failure. Stem cell therapy aims to replace the scar tissue with the functional myocardium. Mesenchymal stem cells (MSCs) are undifferentiated cells capable of self-renewal as well as differentiation into multiple lineages. MSCs can be differentiated into cardiomyocytes by treating them with small molecules and peptides. Here, we report for the first time, the role of a cyclic peptide, an analogue of dianthin G, [Glu2]-dianthin G (1) in the in vitro cardiac differentiation of rat bone marrow MSCs. In this study, [Glu2]-dianthin G (1) was synthesized using solid-phase total synthesis and characterized by NMR spectroscopy. MSCs were treated with two different concentrations (0.025 and 0.05mM) of the peptide separately for 72h and then incubated for 15days to allow the cells to differentiate into cardiomyocytes. Treated cells were analyzed for the expression of cardiac-specific genes and proteins. Results showed significant upregulation of cardiac-specific genes GATA4, cardiac troponin T (cTnT), cardiac troponin I (cTnI), cardiac myosin heavy chain, and connexin 43 in the treated MSCs compared to the untreated control. For cardiac-specific proteins, GATA4, cTnT, and Nkx2.5 were analyzed in the treated cells and were shown to have significant upregulation as compared to the untreated control. In conclusion, this study has demonstrated the cardiac differentiation potential of [Glu2]-dianthin G (1)-treated rat bone marrow MSCs in vitro both at the gene and at the protein levels. Transplantation of pre-differentiated MSCs into the infarcted myocardium may result in the efficient regeneration of cardiac cells and restoration of normal cardiac function.