Methods for Transepicardial Cell Transplantation in a Swine Myocardial Infarction Model

The transplantation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) has garnered significant attention as a potential means of restoring lost muscle mass and contractile function in injured hearts. Early preclinical work with hPSC-CMs employed rodent models, but the field has recently advanced to transplantation studies in more translationally relevant large animal models including non-human primates and swine. The pig is a particularly attractive model for such studies because the size, structure, and physiology of the porcine heart is very similar to that of humans. The pig model has reasonably high throughput, is readily amenable to clinically available cell delivery methods and imaging modalities and has been used frequently to test the safety and efficacy of new cardiac therapies. Here, we describe methods that were established in our laboratory for the specific purpose of testing hPSC-CM transplantation in a pig model of subacute myocardial infarction, but these same techniques should be broadly applicable to the transepicardial delivery of other biologicals including other candidate cell populations, biomaterials, and/or viral vectors.