Stem Cell Factor Gene Transfer Promotes Cardiac Repair After Myocardial Infarction via In Situ Recruitment and Expansion of c-kit+ Cells
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 ckit+ 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 SCF 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 SCF gene transfer (n=13) after myocardial infarction. We found a regenerative response due to SCF 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/β-catenin pathway induction.
Conclusions: SCF 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.
- Received December 26, 2011.
- Accepted August 29, 2012.
- Copyright © 2012, American Heart Association