Open AccessTelomerase/myocardin expressing mesenchymal cells induce survival and cardiovascular markers in cardiac stromal cells undergoing ischaemia/reperfusion
Author(s) -
Madonna Rosalinda,
Guarnieri Simone,
Kovácsházi Csenger,
Görbe Aniko,
Giricz Zoltán,
Geng YongJian,
Mariggiò Maria Addolorata,
Ferdinandy Péter,
De Caterina Raffaele
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16549
Subject(s) - paracrine signalling , mesenchymal stem cell , stromal cell , microbiology and biotechnology , cancer research , biology , chemistry , medicine , receptor
Abstract Cardiac stromal cells (CSCs) contain a pool of cells with supportive and paracrine functions. Various types of mesenchymal stromal cells (MSCs) can influence CSCs in the cardiac niche through their paracrine activity. Ischaemia/reperfusion (I/R) leads to cell death and reduction of the paracrine activity of CSCs. The forced co‐expression of telomerase reverse transcriptase (TERT) and myocardin (MYOCD), known to potentiate anti‐apoptotic, pro‐survival and pro‐angiogenic activities of MSCs isolated from the adipose tissue (AT‐MSCs), may increase CSC survival, favouring their paracrine activities. We aimed at investigating the hypothesis that CSCs feature improved resistance to simulated I/R (SI/R) and increased commitment towards the cardiovascular lineage when preconditioned with conditioned media (CM) or extracellular vesicles (EV) released from AT‐MSCs overexpressing TERT and MYOCD (T/M AT‐MSCs). Murine CSCs were isolated with the cardiosphere (CSps) isolation technique. T/M AT‐MSCs and their secretome improved spontaneous intracellular calcium changes and ryanodine receptor expression in aged CSps. The cytoprotective effect of AT‐MSCs was tested in CSCs subjected to SI/R. SI/R induced cell death as compared to normoxia (28 ± 4 vs 10 ± 3%, P = .02). Pre‐treatment with CM (15 ± 2, P = .02) or with the EV‐enriched fraction (10 ± 1%, P = .02) obtained from mock‐transduced AT‐MSCs in normoxia reduced cell death after SI/R. The effect was more pronounced with CM (7 ± 1%, P = .01) or the EV‐enriched fraction (2 ± 1%, P = .01) obtained from T/M AT‐MSCs subjected to SI/R. In parallel, we observed lower expression of the apoptosis marker cleaved caspase‐3 and higher expression of cardiac and vascular markers eNOS, sarcomeric α‐actinin and cardiac actin. The T/M AT‐MSCs secretome exerts a cytoprotective effect and promotes development of CSCs undergoing SI/R towards a cardiovascular phenotype.