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TISSUE-SPECIFIC STEM CELLS

CD117-Positive Cells in Adult Human Heart Are Localized in the Subepicardium, and Their Activation Is Associated with Laminin-1 and ₆ Integrin Expression

^aDepartment of Biomorphological and Functional Sciences, University Federico II, Naples, Italy;
^bDepartment of Cardiovascular Surgery and Transplantation, Monaldi Hospital, Naples, Italy;
^cKlinik fur Innere Medizin III Kardiologie, Angiologie und Internistische Intensivmedizin, Universitatsklinikum des Saarlandes, Homburg/Saar, Germany

Key Words. Cardiac CD117-positive cells • Heart failure • Extracellular matrix • Laminin

Correspondence: Clotilde Castaldo, M.D., Università degli Studi di Napoli "Federico II," Dipartimento di Scienze Biomorfologiche e Funzionali, via S. Pansini 5, ed. 20, piano II, stanza 205, 80131 Napoli, Italy. Telephone: 39-0817463422; Fax: 39-0815469803; e-mail: clotilde.castaldo{at}unina.it

Received August 31, 2007; accepted for publication April 14, 2008.
First published online in STEM CELLS EXPRESS   April 24, 2008.

CD117-positive cells contributing to cardiac cell turnover in normal and pathological conditions have recently been described in adult human heart. Since the precise spatial and temporal expression of extracellular matrix proteins and their receptors is critical for organ formation, we compared the distribution of cardiac primitive CD117-positive cells in the human adult normal and pathological hearts with ischemic cardiomyopathy, with respect to localization and expression of laminin and integrin isoforms. In the pathological hearts, CD117-positive cells were significantly more numerous than in the normal hearts. They were localized mainly in the atria and were up to 38-fold more numerous in the subepicardium than in the myocardium. Compared with normal hearts, most CD117-positive cells in the subepicardium of pathological hearts were ₆ integrin-positive. Laminin-1, typical of developing heart, was found predominantly in the subepicardium of adult heart. Immunoblotting revealed its highest expression in the normal atrium and pathological left ventricle. Both laminin isoforms reduced apoptosis and increased proliferation and migration of CD117-positive cells in vitro with respect to control, but the effects of laminin-1 significantly outweighed those of laminin-2. Signaling mediated by ₆ integrin was implicated in the migration and protection from apoptosis, as documented by transfection with specific small interfering RNA. These data reveal that the increase in the number of cardiac CD117-positive cells and the expression of laminin-1 are observed in ischemic cardiomyopathy. Subepicardial localization of CD117-positive cells and expression of laminin-1 and ₆ integrin subunits may all correspond to the activation of regeneration involving an epithelial-mesenchymal transition recently described in adult heart.

Disclosure of potential conflicts of interest is found at the end of this article.