Paracrine Engineering of Human Cardiac Stem Cells with Insulin-Like Growth Factor 1 Promotes Cell Survival to Enhance Myocardial Repair

Abstract

Insulin-like growth factor (IGF-1) is a potent pro-survival cytokine that is not robustly expressed by human cardiac stem cells (CSCs). Here, we explore the mechanism underlying IGF-1 enhanced cardiac repair by CSCs. Human CSCs underwent lentiviral- mediated somatic gene transfer of IGF-1 to boost cytokine secretion without adversely blunting the overall cytokine signature of CSCs. In vitro studies demonstrated that IGF-1 provided paracrine and autocrine support that reduced apoptosis by CSCs and cardiomyoctes. In vivo experiments demonstrated that IGF-1 increased CSC-mediated cardiac repair by enhancing salvage of reversibly damaged myocardium and transplanted cell survival.