Published online before print December 1, 2003, doi: 10.1161/01.RES.0000109792.43271.47
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© 2004 American Heart Association, Inc.
Cellular Biology |
Spontaneous Cardiomyocyte Differentiation From Adipose Tissue Stroma Cells
From the UMR 5018 UPS CNRS (V.P.-B., M.A., L.P., L.C.), Research Institute 31, France; CRBS CNRS FRE2593 (C.M., M.P.), Montpellier, France; Clinica Universitaria (A.P.), University of Navarra, Pamplona, Spain and Instituto Cavanilles (J.-M.G.), University of Valencia, Valencia, Spain.
Correspondence to L. Casteilla, UMR 5018 UPS CNRS, IFR31, CHU Rangueil, 1 Av Poulhès, 31054 Toulouse cedex, France. E-mail casteil{at}toulouse.inserm.fr
Cardiomyocyte regeneration is limited in adult life. Thus, the identification of a putative source of cardiomyocyte progenitors is of great interest to provide a usable model in vitro and new perspective in regenerative therapy. As adipose tissues were recently demonstrated to contain pluripotent stem cells, the emergence of cardiomyocyte phenotype from adipose-derived cells was investigated. We demonstrated that rare beating cells with cardiomyocyte features could be identified after culture of adipose stroma cells without addition of 5-azacytidine. The cardiomyocyte phenotype was first identified by morphological observation, confirmed with expression of specific cardiac markers, immunocytochemistry staining, and ultrastructural analysis, revealing the presence of ventricle- and atrial-like cells. Electrophysiological studies performed on early culture revealed a pacemaker activity of the cells. Finally, functional studies showed that adrenergic agonist stimulated the beating rate whereas cholinergic agonist decreased it. Taken together, this study demonstrated that functional cardiomyocyte-like cells could be directly obtained from adipose tissue. According to the large amount of this tissue in adult mammal, it could represent a useful source of cardiomyocyte progenitors.
Key Words: cardiomyocytes • adipose tissue • differentiation • stem cells • cell therapy
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