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Cardiomyogenic Differentiation Potential of Human Dilated Myocardium-Derived Mesenchymal Stem/Stromal Cells: The Impact of HDAC Inhibitor SAHA and Biomimetic Matrices

Authors :
Vytautas Cepla
Agne Vailionyte
Kestutis Rucinskas
Siegfried Labeit
Rokas Miksiunas
Ruta Aldonyte
Vilius Janusauskas
Daiva Bironaite
Gintare Stankeviciene
Ramunas Valiokas
Romuald Eimont
Tadas Jelinskas
Source :
International Journal of Molecular Sciences; Volume 22; Issue 23; Pages: 12702, International Journal of Molecular Sciences, Vol 22, Iss 12702, p 12702 (2021), International journal of molecular sciences, Basel : MDPI, 2021, vol. 22, iss. 23, art. no.12702, p. 1-25, International Journal of Molecular Sciences
Publication Year :
2021
Publisher :
Multidisciplinary Digital Publishing Institute, 2021.

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.

Details

Language :
English
ISSN :
14220067 and 16616596
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences; Volume 22; Issue 23; Pages: 12702
Accession number :
edsair.doi.dedup.....d93c3ff8f05b55a033847c67a88d85d9
Full Text :
https://doi.org/10.3390/ijms222312702