Click chemistry-modified cardiomyocytes enhance cardiac contractility and prevent remodeling in ischemia-reperfusion injured hearts

Abstract

One of the challenges in cardiac cell therapy using cardiomyocytes derived from human pluripotent stem cells (hPSC-CMs) is their poor engraftment and survival rate in infarcted tissues. Click chemistry and lipid insertion are simple methods for modifying the surface of hPSC-CMs with a collagen hybridizing peptide (CHP), providing binding motifs to increase their retention and engraftment in fibrotic hearts after ischemia-reperfusion (I/R) injury. In this study, we developed CHP-modified CMs (CHP-mCMs) to attach cells to damaged collagen in infarcted tissues. We injected CHP-mCMs into the border zone of infarcted hearts 7 days post-MI and evaluated cardiac function for 6 weeks. Serial echocardiography revealed that CHP-mCMs not only improved cardiac function but also reduced adverse remodeling in I/R-injured hearts. These findings indicate that CHP-mCM transplantation was associated with enhanced engraftment, reduced adverse remodeling, and improved cardiac function in the rat I/R model.