Abstract
The non-muscular cells that populate the space found between cardiomyocyte fibers are known as ‘cardiac interstitial cells’ (CICs). CICs are heterogeneous in nature and include different cardiac progenitor/stem cells, cardiac fibroblasts and other cell types. Upon heart damage CICs soon respond by initiating a reparative response that transforms with time into extensive fibrosis and heart failure. Despite the biomedical relevance of CICs, controversy remains on the ontogenetic relationship existing between the different cell kinds homing at the cardiac interstitium, as well as on the molecular signals that regulate their differentiation, maturation, mutual interaction and role in adult cardiac homeostasis and disease. Our work focuses on the analysis of epicardial-derived cells, the first cell type that colonizes the cardiac interstitium. We present here a characterization and an experimental analysis of the differentiation potential and mobilization properties of a new cell line derived from mouse embryonic epicardium (EPIC). Our results indicate that these cells express some markers associated with cardiovascular stemness and retain part of the multipotent properties of embryonic epicardial derivatives, spontaneously differentiating into smooth muscle, and fibroblast/myofibroblast-like cells. Epicardium-derived cells are also shown to initiate a characteristic response to different growth factors, to display a characteristic proteolytic expression profile and to degrade biological matrices in 3D in vitro assays. Taken together, these data indicate that EPICs are relevant to the analysis of epicardial-derived CICs, and are a god model for the research on cardiac fibroblasts and the role these cells play in ventricular remodeling in both ischemic or non/ischemic myocardial disease.
Highlights
IntroductionCardiac muscle cells (cardiomyocytes) are frequently thought to be the most abundant cell type in the adult heart
Cardiac muscle cells are frequently thought to be the most abundant cell type in the adult heart
Our work provides data suggesting that the multipotent properties of cells in the embryonic epicardial lineage are progressively lost throughout development, and the EPIC line represents a post-epithelial-to-mesenchymal transition (EMT) epicardium-derived cells (EPDCs) that can differentiate into myofibroblast-like and fibroblastic cells, but not into myocardial or endothelial cell types
Summary
Cardiac muscle cells (cardiomyocytes) are frequently thought to be the most abundant cell type in the adult heart. Due to the small relative size of cardiac interstitial cells (CICs) and the enormous contribution of cardiomyocytes to cardiac mass, the proportion of CICs versus cardiac muscle cells in the heart is frequently underestimated. The biomedical importance of CICs is illustrated by their massive involvement in the remodeling of cardiac ventricular walls after myocardial infarction, a phenomenon that is characterized by a progressive fibrosis [4] This ventricular remodeling involves the initiation of an inflammatory response and the mobilization of CICs. This ventricular remodeling involves the initiation of an inflammatory response and the mobilization of CICs Both phenomena have been described as a normal response of the adult heart to damage [5]. Other acquired cardiac diseases like dilated cardiomyopathy are characterized by fibrotic disorders [6]
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