Endogenous Cardiac Stem Cell Activation by Insulin-Like Growth Factor-1/Hepatocyte Growth Factor Intracoronary Injection Fosters Survival and Regeneration of the Infarcted Pig Heart

Study Questions:

Does intracoronary administration of IGF-1/HGF promote myocardial repair following acute myocardial infarction (AMI) in pigs?

Methods:

AMI was induced in pigs by a 60-minute balloon occlusion of the left anterior descending (LAD) artery. IGF-1 and HGF were co-administered through the infarct-related artery in a single dose (ranging from 0.5-2 µg HGF and 2-8 µg IGF-1) 30 minutes after coronary reperfusion. Pigs were sacrificed 21 days later for immunohistopathology or 2 months later for cardiac function evaluation by cardiac magnetic resonance imaging.

Results:

IGF-1/HGF increased cardiac progenitor cell number and fostered the generation of new myocardium (both myocytes and microvasculature) in infarcted and peri-infarct/border regions at 21 and 60 days after AMI. Infarct size was reduced with improved left ventricular function at 2 months following AMI.

Conclusions:

Intracoronary administration of IGF-1/HGF following AMI is a practical and effective strategy to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function.

Perspective:

Attempts to regenerate myocardium following MI with cell-based therapies have been largely disappointing, although improved myocardial function in some studies suggests paracrine effects on endogenous cell populations. It would be more practical and possibly more effective if the endogenous cardiac progenitor cell population could be activated with stimulatory factors. This current study in pigs expands on previous studies in mice and dogs that administration of select growth factors following MI may lead to improved myocardial recovery. Elucidation of the precise mechanism by which myocardial improvement occurs with this treatment will require further study.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Somatomedins, Myocardial Infarction, Insulin-Like Growth Factor I, Heart, Biological Markers, Ventricular Function, Left, Stem Cells, Hepatocyte Growth Factor, Myocardial Reperfusion


< Back to Listings