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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
- 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.
- Subjects :
- Cardiomyopathy, Dilated
Male
Stromal cell
TNNT2
QH301-705.5
PTK2
cardiomyogenic differentiation
cardiac mesenchymal stromal cell
hydrogels
histone deacetylase inhibitors
Catalysis
Article
Inorganic Chemistry
Focal adhesion
Biomimetics
medicine
Humans
Regeneration
Myocytes, Cardiac
Physical and Theoretical Chemistry
Biology (General)
Molecular Biology
QD1-999
Spectroscopy
Aged
Cell Proliferation
Vorinostat
Chemistry
Organic Chemistry
Mesenchymal stem cell
ACTC1
Dilated cardiomyopathy
Cell Differentiation
Mesenchymal Stem Cells
General Medicine
Middle Aged
medicine.disease
Computer Science Applications
Case-Control Studies
Cancer research
Histone deacetylase
Subjects
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