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Stem Cell Factor Gene Transfer Promotes Cardiac Repair After Myocardial Infarction via In Situ Recruitment and Expansion of c-kit(+) Cells

E. Yaniz-Galende, J. Q. Chen, E. Chemaly, L. F. Liang, J. S. Hulot, L. McCollum, T. Arias, V. Fuster, K. M. Zsebo and R. J. Hajjar

CircRes.2012 Nov;111(11):1434-U1188.

Abstract: Rationale: There is growing evidence that the myocardium responds to injury by recruiting c-kit(+) cardiac progenitor cells to the damage tissue. Even though the ability of exogenously introducing c-kit(+) cells to injured myocardium has been established, the capability of recruiting these cells through modulation of local signaling pathways by gene transfer has not been tested. Objective: To determine whether stem cell factor gene transfer mediates cardiac regeneration in a rat myocardial infarction model, through survival and recruitment of c-kit(+) progenitors and cell-cycle activation in cardiomyocytes, and explore the mechanisms involved. Methods and Results: Infarct size, cardiac function, cardiac progenitor cells recruitment, fibrosis, and cardiomyocyte cell-cycle activation were measured at different time points in controls (n=10) and upon stem cell factor gene transfer (n=13) after myocardial infarction. We found a regenerative response because of stem cell factor overexpression characterized by an enhancement in cardiac hemodynamic function: an improvement in survival; a reduction in fibrosis, infarct size and apoptosis; an increase in cardiac c-kit(+) progenitor cells recruitment to the injured area; an increase in cardiomyocyte cell-cycle activation; and Wnt/beta-catenin pathway induction. Conclusions: Stem cell factor gene transfer induces c-kit(+) stem/progenitor cell expansion in situ and cardiomyocyte proliferation, which may represent a new therapeutic strategy to reverse adverse remodeling after myocardial infarction. (Circ Res. 2012;111:1434-1445.)

*Times cited: 3

Keywords: cardiac myocyte regeneration, gene transfer, myocardial infarction, stem, cell factor, randomized phase-1 trial, c-kit ligand, beta-catenin, heart-disease, self-renewal, adult heart, progenitors, expression, receptor, mouse


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