Abstract P1114: Preclinical Large Animal Assessment Of Safety And Engraftment Of Hicms Nanofiber Cardiac Patch Transplantation For Cardiac Repair

Abstract

Background: Myocardial infarction (MI) is a leading cause of death in the United States. However, none of the therapies can regenerate the damaged heart muscle. Objective: The objective of this study was to assess the safety and engraftment of a nanofiber cardiac patch laden with human iPSC-derived cardiomyocytes (hiCMs) and transplanted in a preclinical porcine MI model. Methodology: MI was induced in pigs via advancing a balloon catheter from the femoral artery into the left anterior descending coronary artery (LAD) below the first diagonal branch (D1) and the balloon was inflated for 90-min to induce myocardial ischemia. Immunosuppressant drug Tacrolimus was given orally one-week before the cardiac patch transplantation and continued for up to 4-weeks post-cardiac patch transplantation. Epicardial transplantation of aligned nanofiber cardiac patch (2 layers) loaded with hiCMs was performed at one-week post MI. Magnetic resonance Imaging (MRI) was performed prior to the MI induction (Baseline), 1-week post-MI and at 4-weeks post cardiac patch transplantation to assess severity of MI and cardiac function. At 4-weeks post-MI, pigs were euthanized, and the heart tissues were processed for immunostaining to confirm the retention and engraftment (Human Nuclear Antibody staining) of the implanted cells in the host myocardium. Results: (a) A significant increase in ST-elevation following 90-min of MI, (b) Incidence of cardiac arrhythmias were not observed post cardiac patch transplantation, confirming the safety of cardiac patch, (c) No teratomas were observed at the transplanted site, indicating safety of terminally differentiated hiCMs and (d) Immunofluorescence staining of cardiac sections in the transplanted cardiac patch area confirmed engraftment of transplanted cells via anti-human nuclear antibody, which demonstrates the survival and engraftment of implanted cells. Conclusions: In summary, we have demonstrated for the first time that aligned nanofiber cardiac patch loaded with hiCMs is safe and can enhance retention of transplanted cells. Further studies are warranted to assess the long-term efficacy of cardiac patch transplantation in improving the cardiac function and to perform first-in-human clinical trials in the near future.