Abstract P1009: Size And Distribution Of Human Cardiac Tissue Grafts Following Transendocardial Delivery Of Committed Cardiac Progenitors In A Swine Ischemic Heart Failure Model

Abstract

Introduction: iPSC-derived committed cardiac progenitor cells (CCP) have exciting potential to remuscularize infarcted myocardium; however, little is known about CCP engraftment and differentiation following injection. We hypothesized that transendocardial injection (TEI) of CCPs with an injectable cardiac fibroblast derived extracellular matrix (ECM) retention agent would result in cardiac tissue grafts in an immunosuppressed porcine ischemic heart failure (HF) model. Methods: Coronary artery balloon-occlusion myocardial infarction was induced in Yucatan mini-swine. After 1 month, 300M CCPs with and without 50 mg ECM particles were delivered in 15 intramyocardial injections to the border zone and infarct zone using a steerable Myostar injection catheter with NOGA XP mapping. Immunosuppressed swine were sacrificed up to 2 months following treatment. Hearts were systematically sectioned and stained for human nuclear antigen (Ku80) and cardiac troponin I/T to define the area and distribution of human grafts and cardiomyocyte content. Results: Clusters of human grafts composed of predominantly troponin positive cardiomyocytes were observed in the infarct, at the infarct border, and in adjacent healthy tissue. Overall, 21/25 (84%) of treated pigs had human cardiac tissue grafts. In the current analysis, grafts were identified in 11/12 (91.6%) and 10/13 (76.9%) of pigs in the CCP+ECM and CCP, respectively (see Figure). The observed mean graft area was 62,930 ± 40,332 μm 2 and 185,200 ± 329,080 μm 2 per pig in the CCP+ECM and CCP only groups, respectively (p=0.23). Conclusion: In an immunosuppressed swine ischemic HF model, TEI of CCPs ± ECM yields persistent human cardiac tissue grafts composed of predominantly of cardiomyocytes in both infarcted and non-infarcted regions of the myocardium up to 2 months following treatment.