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Updated: Jul 10, 2026

In Vitro Culture of Epicardial Cells From Mouse Embryonic Heart
Published on: April 27, 2016
Identification of myocardial and vascular precursor cells in human and mouse epicardium
Federica Limana1, Antonella Zacheo, David Mocini
1Laboratorio di Biologia Vascolare e Terapia Genica, Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico, Milan.
Insights
Adult epicardium retains stem cells that can regenerate heart tissue after injury. These c-kit(+) and CD34(+) cells differentiate into vascular and potentially myocardial cells, offering new avenues for cardiac repair research.
Area of Science:
- Cardiovascular Biology
- Stem Cell Research
- Regenerative Medicine
Background:
- The epicardium, a transient layer during development, is a source of multipotent cells.
- Its role in adult cardiac tissue and potential for regeneration remain incompletely understood.
Purpose of the Study:
- To determine if stem cells reside in adult human and murine epicardium.
- To investigate the regenerative potential of these epicardial stem cells post-myocardial infarction.
Main Methods:
- Detection and characterization of c-kit(+) and CD34(+) cells in fetal and adult epicardium.
- In vitro differentiation assays to assess endothelial potential.
- Murine model of myocardial infarction to study epicardial cell response and differentiation in vivo.
Main Results:
- c-kit(+) and CD34(+) cells, distinct from hematopoietic lineage (CD45-negative), are present in adult epicardium.
- These cells express cardiac transcription factors and can adopt an endothelial phenotype in vitro.
- Epicardial c-kit(+) cells increase, proliferate, and migrate into damaged areas post-myocardial infarction, differentiating into vascular cells.
Conclusions:
- The postnatal epicardium harbors stem cells with potential for cardiac regeneration.
- These cells can differentiate into vascular and possibly myocardial lineages, contributing to repair after injury.
Abstract:
During cardiac development, the epicardium is the source of multipotent mesenchymal cells, which give rise to endothelial and smooth muscle cells in coronary vessels and also, possibly, to cardiomyocytes. The aim of the present study was to determine whether stem cells are retained in the adult human and murine epicardium and to investigate the regenerative potential of these cells following acute myocardial infarction. We show that c-kit(+) and CD34(+) cells can indeed be detected in human fetal and adult epicardium and that they represent 2 distinct populations. Both subsets of cells were negative for CD45, a cell surface marker that identifies the hematopoietic cell lineage. Immunofluorescence revealed that freshly isolated c-kit(+) and CD34(+) cells expressed early and late cardiac transcription factors and could acquire an endothelial phenotype in vitro. In the murine model of myocardial infarction, there was an increase in the absolute number and proliferation of epicardial c-kit(+) cells 3 days after coronary ligation; at this time point, epicardial c-kit(+) cells were identified in the subepicardial space and expressed GATA4. Furthermore, 1 week after myocardial infarction, cells coexpressing c-kit(+), together with endothelial or smooth muscle cell markers, were identified in the wall of subepicardial blood vessels. In summary, the postnatal epicardium contains a cell population with stem cell characteristics that retains the ability to give rise to myocardial precursors and vascular cells. These cells may play a role in the regenerative response to cardiac damage.

