PURPOSE: Myocardial infarction (MI) remains a major cause of mortality because of the limited regenerative capacity of the myocardium. Transplantation of somatic tissue-derived cells into the heart has been shown to enhance the endogenous healing process, but the magnitude of its therapeutic effects is dependent upon the cell-source or cell-delivery method. We investigated the therapeutic effects of C-Kit positive cardiac cell (CSC) cell-sheet transplantation therapy in a rat model of MI. METHODS AND RESULTS: CSCs of human origin were sorted and cultured to generate scaffold-free CSC cell-sheets. One-layered or 3-layered cell-sheets were transplanted into nude rats 1 h after left coronary artery ligation. We observed a significant increase in the left ventricular ejection fraction and a significant decrease in left ventricular systolic dimension at 2 and 4 weeks in the 3-layer group, but not in the 1-layer or sham groups. Consistently, there was less accumulation of interstitial fibrosis in the 3-layer group than in the 1-layer or sham groups. Moreover, capillary density was significantly greater in the 3-layer group than in the 1-layer or sham groups. CONCLUSIONS: The 3-layered cell-sheet improved cardiac function associated with angiogenic and anti-fibrotic effects. Thus, CSC is a promising cell-source to use with the cell-sheet method for the treatment of cardiac failure, as long as a sufficient number of cells are delivered.
PURPOSE:Myocardial infarction (MI) remains a major cause of mortality because of the limited regenerative capacity of the myocardium. Transplantation of somatic tissue-derived cells into the heart has been shown to enhance the endogenous healing process, but the magnitude of its therapeutic effects is dependent upon the cell-source or cell-delivery method. We investigated the therapeutic effects of C-Kit positive cardiac cell (CSC) cell-sheet transplantation therapy in a rat model of MI. METHODS AND RESULTS: CSCs of human origin were sorted and cultured to generate scaffold-free CSC cell-sheets. One-layered or 3-layered cell-sheets were transplanted into nude rats 1 h after left coronary artery ligation. We observed a significant increase in the left ventricular ejection fraction and a significant decrease in left ventricular systolic dimension at 2 and 4 weeks in the 3-layer group, but not in the 1-layer or sham groups. Consistently, there was less accumulation of interstitial fibrosis in the 3-layer group than in the 1-layer or sham groups. Moreover, capillary density was significantly greater in the 3-layer group than in the 1-layer or sham groups. CONCLUSIONS: The 3-layered cell-sheet improved cardiac function associated with angiogenic and anti-fibrotic effects. Thus, CSC is a promising cell-source to use with the cell-sheet method for the treatment of cardiac failure, as long as a sufficient number of cells are delivered.
Authors: Marcello Rota; M Elena Padin-Iruegas; Yu Misao; Antonella De Angelis; Silvia Maestroni; João Ferreira-Martins; Emanuela Fiumana; Raffaella Rastaldo; Michael L Arcarese; Thomas S Mitchell; Alessandro Boni; Roberto Bolli; Konrad Urbanek; Toru Hosoda; Piero Anversa; Annarosa Leri; Jan Kajstura Journal: Circ Res Date: 2008-06-12 Impact factor: 17.367
Authors: Mónika Szepes; Zsolt Benkő; Attila Cselenyák; Kai Michael Kompisch; Udo Schumacher; Zsombor Lacza; Levente Kiss Journal: Stem Cells Int Date: 2013-06-19 Impact factor: 5.443