Safety and Engraftment of Aligned Cardiac Patches Loaded with hiPSC-CMs in a Large Animal Model of Myocardial...

Myocardial infarction (MI) is a leading cause of death in the United States. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) present a promising strategy for regenerating the damaged heart tissue post-MI. However, poor cell engraftment and survival remain significant barriers in their effective use for myocardial repair. In this study, we developed a "cardiac patch" using a bi-layered, aligned coaxial patch for epicardial delivery of hiPSC-CMs in a preclinical porcine MI model. The cardiac patch (40 mm in diameter and 500 µm thick) was fabricated using polycaprolactone (PCL) and gelatin via electrospinning and seeded with twenty-two million hiPSC-CMs. In vitro functional assessment showed synchronized contractility of the hiPSC-CMs along the aligned fibers. The in vivo transplantation of the cardiac patch was performed in a translationally relevant preclinical large animal (porcine) MI model at 1-week after MI induction. Histological assessments showed successful engraftment and survival of the hiPSC-CMs at the infarct, up to 4-weeks after cardiac patch-transplantation. This was accompanied by modest improvements in LVEF (Patch:18.0% vs Control: -1.2%) and a decrease in the enhancement percentage (Patch: 28.8% vs Control: 18.6%) at 4-weeks post-patch transplantation. Additionally, absence of arrhythmias or teratoma formation, affirmed the safety of the cardiac patch. Overall, we have demonstrated the feasibility, safety and engraftment of bi-layered aligned cardiac patches seeded with hiPSC-CMs in preclinical porcine MI model as a promising therapeutic approach for myocardial regeneration post-MI.