TY - JOUR
T1 - Identification of myocardial and vascular precursor cells in human and mouse epicardium
AU - Limana, Federica
AU - Zacheo, Antonella
AU - Mocini, David
AU - Mangoni, Antonella
AU - Borsellino, Giovanna
AU - Diamantini, Adamo
AU - De Mori, Roberta
AU - Battistini, Luca
AU - Vigna, Elisa
AU - Santini, Massimo
AU - Loiaconi, Vincenzo
AU - Pompilio, Giulio
AU - Germani, Antonia
AU - Capogrossi, Maurizio C.
PY - 2007/12
Y1 - 2007/12
N2 - 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.
AB - 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.
KW - Cardiovascular differentiation
KW - Epicardium
KW - Infarction
KW - Stem cells
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U2 - 10.1161/CIRCRESAHA.107.150755
DO - 10.1161/CIRCRESAHA.107.150755
M3 - Article
C2 - 17947800
AN - SCOPUS:37349012572
VL - 101
SP - 1255
EP - 1265
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 12
ER -