Effect of equiaxial cyclic strain on cardiomyogenic induction in mesenchymal stem cells

Abstract

Differentiation of stem cells and functionality of target cells are regulated by microenvironmental stimuli to which the cells are exposed. Chemical agents such as growth factors and physical parameters including mechanical loadings are among major stimuli. In this study, equiaxial cyclic strain with two amplitudes was applied on rat adipose-derived mesenchymal stem cells (rAMSCs) with or without 5-azacytidine. The mRNA expression of cardiac-related genes was investigated through RT-PCR (polymerase chain reaction) method. Moreover, morphological features and the actin structure of the cells were studied. Results were indications of significant increase in mRNA expression among four target genes, which marked the increase in two principal cardiac markers of GATA4 and α-cardiac actin, and lesser increase in two other genes (NKX2-5, βMHC) in all experimental groups treated chemically and/or mechanically. Such effect was maximal when both treatments were applied describing the synergistic effect of combined stimuli. All treatments caused significant increase in cell area and cell shape index. The well spreading of cells was accompanied by enhanced actin structure, especially among samples subjected to mechanical stimulus. Both effects were among required features for functional muscle cells such as cardiac cells. It was concluded that the cyclic equiaxial strain enhanced cardiomyogenic induction among rat adipose-derived mesenchymal stem cells and such effect was strengthened when it was accompanied by application of chemical factor. Results can be considered among strategies for cardiomyogenic differentiation and can be employed in cardiac tissue engineering for production of functional cardiomyocytes to repair of damaged myocardium.