Abstract 1268: Epicardial Tissue is a Source of Cells Expressing Early Endothelial and Myocardial Markers
Background: During development, the epicardium is the source of multipotent mesenchymal cells which give rise to coronary vessels, including endothelial cells, smooth muscle cells and, possibly, also cardiomyocytes. Aim of the present study was to determine the presence of cells with stem cell characteristics in the adult human and murine epicardium and, eventually, the effect of myocardial infarction on these cells.
Methods and Results: Cells expressing stem cell antigens c-kit and CD34 were detected by immunohistochemical analysis in the epicardial region of human fetal and adult myocardium. In the adult human heart this compartment is mostly occupied by adipose tissue which surrounds the main coronary arteries and veins. By flow cytometric analysis it was shown that c-kit+ and CD34+ cells were two distinct populations and represented 0.5±0.1% and 4.8±2% (n=5) of total cells, respectively. Both subsets of cells were negative for CD45, a cell surface marker which identifies the hematopoietic cell lineage. Immunofluorescence revealed that some of freshly isolated c-kit+ and CD34+ cells expressed the early cardiac transcription factors GATA4 and Nkx2.5. Magnetic-sorted c-kit+ and CD34+ cells, cultured on fibronectin with RPMI-20%FCS, adhered, elongated and 10–15% of cells acquired endothelial cell specific phenotype, as evidenced with the incorporation of Ac-LDL-DiI. Differently from human, murine epicardium is only constituted by a layer of mesothelial cells; c-kit+ and CD34+ cells were 9±2.6% and 3.5±0.1%; (n=6). In the murine model of myocardial infarction, epicardial c-kit+ increased of 5 fold at day 3 after infarction; at this time c-kit+ cells expressing GATA4 were also present in the sub-epicardial space. In the absence of infarction, c-kit+ cells were not detected in the coronoray artery wall; however after infarction cells co-expressing c-kit+ together with endothelial marker factor VII were identified in the wall of vessels located in the sub-epicardial space.
Conclusions: The post-natal epicardium contains a cell population with stem cell characteristics which retains the ability to give origin to cardiac precursors and endothelial cells. These cells may play a role in the regenerative response to cardiac damage.