Abstract
BackgroundSkeletal myoblast transplantation seems a promising approach for the repair of myocardial infarction (MI). However, the low engraftment efficacy and impaired angiogenic ability limit the clinical efficiency of the myoblasts. Gene engineering with angiogenic growth factors promotes angiogenesis and enhances engraftment of transplanted skeletal myoblasts, leading to improved infarction recovery in myocardial ischemia. The present study evaluated the therapeutic effects of hepatocyte growth factor (HGF) gene-engineered skeletal myoblasts on tissue regeneration and restoration of heart function in a rat MI model.Methods and resultsThe skeletal myoblasts were isolated, expanded, and transduced with adenovirus carrying the HGF gene (Ad-HGF). Male SD rats underwent ligation of the left anterior descending coronary artery. After 2 weeks, the surviving rats were randomized into four groups and treated with skeletal myoblasts by direct injection into the myocardium. The survival and engraftment of skeletal myoblasts were determined by real-time PCR and in situ hybridization. The cardiac function with hemodynamic index and left ventricular architecture were monitored; The adenovirus-mediated-HGF gene transfection increases the HGF expression and promotes the proliferation of skeletal myoblasts in vitro. Transplantation of HGF-engineered skeletal myoblasts results in reduced infarct size and collagen deposition, increased vessel density, and improved cardiac function in a rat MI model. HGF gene modification also increases the myocardial levels of HGF, VEGF, and Bcl-2 and enhances the survival and engraftment of skeletal myoblasts.ConclusionsHGF engineering improves the regenerative effect of skeletal myoblasts on MI by enhancing their survival and engraftment ability.
Highlights
Various approaches have greatly advanced in the diagnosis and treatment of cardiovascular diseases, heart failure remains the leading cause of mortality in elderly patients [1]
The present study evaluated the therapeutic effects of hepatocyte growth factor (HGF) gene-engineered skeletal myoblasts on tissue regeneration and restoration of heart function in a rat myocardial infarction (MI) model
HGF engineering improves the regenerative effect of skeletal myoblasts on MI by enhancing their survival and engraftment ability
Summary
Various approaches have greatly advanced in the diagnosis and treatment of cardiovascular diseases, heart failure remains the leading cause of mortality in elderly patients [1]. The major pathophysiological features for mortality caused by chronic heart failure (CHF) include left ventricular (LV) dysfunction and heart remodeling post-infarction. Cell therapy is emerging as a promising regenerative approach to treating all stages of heart failure following myocardial infarction (MI) [2]. Several strategies including physiological pretreatment, anti-apoptosis, and angiogenic gene transfection have been evaluated for improving the cell engraftment [6,7,8,9]. Gene engineering with angiogenic growth factors promotes angiogenesis and enhances engraftment of transplanted skeletal myoblasts, leading to improved infarction recovery in myocardial ischemia. The present study evaluated the therapeutic effects of hepatocyte growth factor (HGF) gene-engineered skeletal myoblasts on tissue regeneration and restoration of heart function in a rat MI model
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
