Characterization of epicardial-derived cardiac interstitial cells: differentiation and mobilization of heart fibroblast progenitors

PLoS One. 2013;8(1):e53694. doi: 10.1371/journal.pone.0053694. Epub 2013 Jan 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation*
  • Cell Line
  • Cell Movement*
  • Embryonic Stem Cells / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Multipotent Stem Cells / cytology
  • Myofibroblasts / cytology*
  • Pericardium / cytology*
  • Pericardium / embryology
  • Pericardium / metabolism
  • Proteolysis
  • Stem Cell Niche


  • Biomarkers

Grants and funding

This work was funded by grants LSHM-CT-2005-018630 (‘HeartRepair’, EU FP6), ‘CardioNet’ (EU FP7 Marie Curie Programme ITNs), P08-CTS-03618 (Junta de Andalucía, Spain) and the Spanish Ministry of Economy (MINECO) grants BFU2009-07929 and RD06/0010/0015 (TERCEL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.