Key result
Epicardial c-kit+ CPC sheets reduce post-MI scar size ~2-fold vs. control.
Why the study?
Clinical studies of direct cardiac progenitor cell injection have shown low engraftment rates that limit beneficial effects, prompting investigation of cell sheet transplantation to facilitate longer cell retention and improve regeneration after myocardial infarction.
Does epicardial transplantation of c-kit+ cardiac progenitor cell sheets improve myocardial vascularization and attenuate left ventricular remodeling in a rat model of myocardial infarction?
Does epicardial transplantation of c-kit+ cardiac progenitor cell sheets improve myocardial vascularization and attenuate left ventricular remodeling in a rat model of myocardial infarction?
Answers are grounded in this paper and cite their sources.
Preclinical study in rats demonstrating that scaffold-free c-kit+ cardiac progenitor cell sheets improve cell retention, promote neovascularization, and attenuate post-MI adverse LV remodeling primarily via paracrine mechanisms rather than direct cardiomyogenesis.
The adult heart contains small populations of multipotent cardiac progenitor cells (CPC) that present a convenient and efficient resource for treatment of myocardial infarction. Several clinical studies of direct CPC delivery by injection have already been performed but showed low engraftment rate that limited beneficial effects of procedure. «Cell sheet» technology has been developed to facilitate longer retention of grafted cells and show new directions for cell-based therapy using this strategy. In this study we hypothesized that СPC-based cell sheet transplantation could improve regeneration after myocardial infarction. We demonstrated that c-kit+ CPC were able to form cell sheets on temperature-responsive surfaces. Cell sheet represented a well-organized structure, in which CPC survived, retained ability to proliferate, expressed progenitor cell marker Gata-4 formed connexin-43+ gap junctions, and were surrounded by significant amount of extracellular matrix proteins. Transplantation of cell sheets after myocardial infarction resulted in CPC engraftment as well as their proliferation, migration, and differentiation; cell sheets also stimulated neovascularization and cardiomyocyte proliferation in underlining myocardium and ameliorated left ventricular remodeling. Obtained data strongly supported potential use of CPC sheet transplantation for repair of damaged heart.
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Дергилев et al. (2018) studied Experimental myocardial infarction in rats (n=70). c-kit+ cardiac progenitor cell (CPC) sheet epicardial transplantation vs. Control (MI surgery without cell sheet transplantation, n=28) and sham operation (n=20) was evaluated on Postinfarction scar size and left ventricular remodeling at day 14. Epicardial c-kit+ CPC sheet transplantation reduced postinfarction scar size approximately 2-fold and increased LV wall thickness by ~13% at day 14 compared to control in rats with MI.
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