Abstract P1051: Minimally Invasive Delivery Of Synthetic Cardiac Stromal Cells In A Large Animal Model Of Myocardial Infarction

Abstract

Cell therapies for cardiac tissue regeneration are commonly used for tissue remolding post-MI, however, due to viability, retention, and cost, acellular therapeutic components are being explored. Synthetic cardiac stromal cells (synCSCs) generated by encapsulating secreted factors from isolated human cardiac stromal cells were shown to promote cardiac repair after MI. Previously, synCSCs implantation required surgy. Reducing the risks of surgical complications is essential for translational research. It is beneficial to develop a minimally invasive approach such as intrapericardial cavity (iPC) injections. This pre-clinical study aims to elucidate the therapeutic effects of synCSC embedded in hyaluronic acid (HA) hydrogel on a large animal model of MI through iPC injection. HA hydrogel and synCSCs are fabricated according to previous studies. Video-assisted thoracoscopic surgery is performed for iPC injections in Yorkshire male pigs. Magnetic resonance imaging (MRI) and immunohistochemistry (IHC) data were collected for cardiac function analyses. This pre-clinical study aims to bridge the gap between the bench and bedside by using a minimally invasive approach of iPC injection of synCSCs embedded in the hydrogel. Figure 1 shows iPC injection of synCSCs in HA improved cardiac function and cardiomyocyte proliferation in the pig MI model. Single-cell RNA sequencing data is being analyzed to identify gene markers elevated by synCSC treatment and further uncover the molecular pathways activated by synCSC. iPC injection of synCSC provides a unique dataset in the field of cardiac tissue regeneration and offers another therapeutic option for patients suffering from MI.