Abstract P1093: Safety And Feasibility Of Tissue-engineered Biological Ventricular Assist Devices For Ischemic Cardiomyopathy

Abstract

Introduction: Advances in material science and cell technology offer new possibilities in myocardial repair. We test the safety and feasibility of implanting epicardial cellularized patches in a porcine ischemic cardiomyopathy model, representative of human disease. Methods: In pigs (n=4) , 90 min occlusion of the circumflex artery induced myocardial infarction (MI) (infarct size at 4w MRI: 16±7% of LV mass with reduced EF 49±12%). To cover the scar, hexagonal multi-layered 4x4cm scaffolds were printed using high-resolution 3D melt electrowriting, and populated with human iPSC-derived cells (90% cardiomyocytes/10% fibroblasts, totaling 90 million cells), loaded in fibrin hydrogel. Four w post-MI and after 2 w immunosuppression, we sutured patches over the infarcted epicardium and monitored arrhythmias with implantable loop recorders for 1 w. Hearts were explanted after a second MRI for histopathology. Results: Pre-implantation cell loss from spontaneously contracting patches was 0.34±0.15% of all iPSC-derived cells. Immunosuppression was well tolerated (normal LFTs and eGFR) and effective and no significant arrhythmias were recorded after patch implantation. MRI showed correct anatomical patch position ( Fig. 1 ). Visual analysis confirmed homogeneous patch attachment and histology evidenced excellent biocompatibility, and marked engraftment of the construct with host vasculature ( Fig. 1 ). Conclusions: We provide proof-of-concept for safety and feasibility of human iPSC-derived cellular constructs of clinically relevant size in porcine ischemic cardiomyopathy. Follow-up placebo-controlled studies are ongoing to evaluate therapeutic efficacy.