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

Nasim Rezaee,Nooshin Haghighipour,Mohammad Tafazzoli-Shadpour

doi:10.1007/s40204-018-0102-5

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.

Highlights

Full disability of tissue or its loss is among destructive medical conditions which require expensive and time-consuming treatment strategies
To further evaluate the effectiveness of new methods to induce cardiomyogenic differentiation among Myocardial infarction is a permanentMesenchymal stem cells (MSCs), and to obtain a better insight of the role of mechanical stimuli in cardiovascular development and remodeling, here we investigated the effects of equiaxial cyclic strain on cardiomyogenic fate of rat adipose-derived mesenchymal stem cells
Test groups included two groups of cells subjected to cyclic equiaxial strain with two amplitudes of 5% or 10%, cells treated by chemical factor (5azacytidine), and samples subjected to 10% cyclic equiaxial stretch accompanied by chemical factor (5azacytidine)

Summary

Introduction

Full disability of tissue or its loss is among destructive medical conditions which require expensive and time-consuming treatment strategies. Mesenchymal stem cells (MSCs) are capable of selfrenewal and differentiating into other cell types (Pountos et al 2007). MSCs have been used for in vitro differentiation into beating cardiomyocytes (Haraguchi et al 2012), in vivo repair of myocardium (Vidarsson et al 2010), and myocardial infarction therapy (Fisher et al 2015). Exploring the microenvironment of MSCs provides a better understanding of differentiation towards functional cells and reconstruction of damaged tissues. This has led scholar research to provide similar environmental conditions and stimuli during in vitro differentiation of stem cells to obtain well-functioning target cells. Current methods that are employed for the differentiation of stem cells involve the use of biochemical agents, physical factors such as mechanical, electrical, thermal and electromagnetic stimuli, and co-culture with other cells (Maul et al 2011; Kavand et al 2016; Pires et al 2015)

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