Circulation Research. 2004;95:911-921
Published online before print October 7, 2004, doi: 10.1161/01.RES.0000147315.71699.51
Published online before print October 7, 2004, doi: 10.1161/01.RES.0000147315.71699.51
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© 2004 American Heart Association, Inc.
Cellular Biology |
Isolation and Expansion of Adult Cardiac Stem Cells From Human and Murine Heart
From the Department of Experimental Medicine and Pathology (E.M., S.M., M.V.G.L., L.F., A.G.), University La Sapienza, Rome; IRCCS "Neuromed (E.M., S.M., M.V.G.L., L.F., A.G.)," Pozzilli (IS); Department of Histology and Medical Embriology (L.D.A., M.C., E.V., G.C.), University La Sapienza, Rome; Campus-Biomedico University (G.F.), Rome; Institute of Neurobiology and Molecular Medicine (M.B.), Consiglio Nazionale delle Ricerche, Rome; Stem Cell Research Institute (G.S.), Ospedale San Raffaele, Milan; Istituto di Ricerche Farmacologiche "Mario Negri" (S.C., F.F., M.S.), Milan, Italy.
Correspondence to Alessandro Giacomello, Department of Experimental Medicine and Pathology, University La Sapienza, 00161 Rome, Italy; E-mail alessandro.giacomello{at}uniroma1.it; and to Giulio Cossu, Department of Histology and Medical Embriology, University La Sapienza, 00161 Rome, Italy. E-mail giulio.cossu@uniromal.it
Cardiac myocytes have been traditionally regarded as terminally differentiated cells that adapt to increased work and compensate for disease exclusively through hypertrophy. However, in the past few years, compelling evidence has accumulated suggesting that the heart has regenerative potential. Recent studies have even surmised the existence of resident cardiac stem cells, endothelial cells generating cardiomyocytes by cell contact or extracardiac progenitors for cardiomyocytes, but these findings are still controversial. We describe the isolation of undifferentiated cells that grow as self-adherent clusters (that we have termed "cardiospheres") from subcultures of postnatal atrial or ventricular human biopsy specimens and from murine hearts. These cells are clonogenic, express stem and endothelial progenitor cell antigens/markers, and appear to have the properties of adult cardiac stem cells. They are capable of long-term self-renewal and can differentiate in vitro and after ectopic (dorsal subcutaneous connective tissue) or orthotopic (myocardial infarction) transplantation in SCID beige mouse to yield the major specialized cell types of the heart: myocytes (ie, cells demonstrating contractile activity and/or showing cardiomyocyte markers) and vascular cells (ie, cells with endothelial or smooth muscle markers).
Key Words: adult stem cell • myocardial regeneration and angiogenesis
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