Abstract
Dilated cardiomyopathy (DCM) is the most common type of nonischemic cardiomyopathy characterized by left ventricular or biventricular dilation and impaired contraction leading to heart failure and even patients’ death. Therefore, it is important to search for new cardiac tissue regenerating tools. Human mesenchymal stem/stromal cells (hmMSCs) were isolated from post-surgery healthy and DCM myocardial biopsies and their differentiation to the cardiomyogenic direction has been investigated in vitro. Dilated hmMSCs were slightly bigger in size, grew slower, but had almost the same levels of MSC-typical surface markers as healthy hmMSCs. Histone deacetylase (HDAC) activity in dilated hmMSCs was 1.5-fold higher than in healthy ones, which was suppressed by class I and II HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) showing activation of cardiomyogenic differentiation-related genes alpha-cardiac actin (ACTC1) and cardiac troponin T (TNNT2). Both types of hmMSCs cultivated on collagen I hydrogels with hyaluronic acid (HA) or 2-methacryloyloxyethyl phosphorylcholine (MPC) and exposed to SAHA significantly downregulated focal adhesion kinase (PTK2) and activated ACTC1 and TNNT2. Longitudinal cultivation of dilated hmMSC also upregulated alpha-cardiac actin. Thus, HDAC inhibitor SAHA, in combination with collagen I-based hydrogels, can tilt the dilated myocardium hmMSC toward cardiomyogenic direction in vitro with further possible therapeutic application in vivo.
Highlights
We have investigated the levels of mesenchymal stem/stromal (MSC) origin biomarkers, growth intensity, and Histone deacetylase (HDAC) activity in dilated myocardium derived-MSC comparing to the Human mesenchymal stem/stromal cells (hmMSCs) derived from the normal functioning myocardium in vitro
HmMSC isolated from dilated human myocardium (Figure 1C) were bigger in shape and grew flatter on the plastic surface than hmMSC isolated from the healthy myocardium (Figure 1B)
Data from this study show that expression of cardiomyogenic differentiationrelated genes such as cardiac actin and troponin T in dilated myocardium-derived hmMSC
Summary
Dilated cardiomyopathy (DCM) refers to heterogeneous myocardial disorders characterized by ventricle dilation and depressed myocardial performance [1]. It starts in the left ventricle and initiates chamber dilation, wall stretching, and thinning. Changed volume of the left ventricle further spreads to the right ventricle and to the atria subsequently leading to the dilation of the whole heart [2]. Dilated cardiomyopathy and its further complications (heart failure, arrhythmias, thrombosis) are among the leading global causes of human mortality [3]. Current DCM treatment strategies are not always successful and often lead to heart transplantation. New technologies modifying heart cells and/or extracellular environment to restore and/or regenerate damaged heart tissue remain relevant these days
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