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(Circulation Research. 2007;101:1255.)
© 2007 American Heart Association, Inc.

Cellular Biology

Identification of Myocardial and Vascular Precursor Cells in Human and Mouse Epicardium

Federica Limana^*, Antonella Zacheo^*, David Mocini, Antonella Mangoni, Giovanna Borsellino, Adamo Diamantini, Roberta De Mori, Luca Battistini, Elisa Vigna, Massimo Santini, Vincenzo Loiaconi, Giulio Pompilio, Antonia Germani, Maurizio C. Capogrossi

From the Laboratorio di Biologia Vascolare e Terapia Genica (F.L., G.P., A.G.), Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico, Milan; Laboratorio di Patologia Vascolare (A.Z., A.M., R.D.M., M.C.C.), Istituto Dermopatico dell’Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Rome; Ospedale San Filippo Neri (D.M., M.S., V.L.), Rome; Fondazione Santa Lucia (G.B., A.D., L.B.), Rome; Istituto per la Ricerca sul Cancro (E.V.), Università di Torino; and Fondazione Livio Patrizi (A.G.), Laboratori di Ricerca Gruppo Bios, Rome, Italy.

Correspondence to Maurizio C. Capogrossi, Laboratorio di Patologia Vascolare, Istituto Dermopatico dell’Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico-IDI, Via dei Monti di Creta 104, 00167 Rome, Italy. E-mail capogrossi{at}idi.it

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.

Key Words: epicardium • infarction • stem cells • cardiovascular differentiation

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