Abstract 206: Electrical Stimulation Enhances the Therapeutic Potential of Pediatric Cardiac Progenitor Cells

Nearly 1 in every 120 children born has a congenital heart defect, and many of these children go on to develop heart failure (HF). The emergence of cardiovascular regenerative medicine as a potential therapeutic strategy for pediatric HF has provided new avenues for treatment. Stem cells such as cardiac progenitor cells (CPCs) have shown promise in restoring cardiac function in adult pathologies; however, few studies have focused on the pediatric population. Recently, pediatric CPCs >1year old have been shown to have reduced efficacy compared to younger cells. This indicates a need to enhance the regenerative potential of this population of cells for an autologous treatment for HF in pediatric patients. The regenerative potential of adult stem cells can be enhanced by ex vivo manipulation, and electrical stimulation (ES) is one such treatment we have examined in pediatric CPCs. We have previously shown that pediatric CPCs (1-5 years old) respond to ES by initiating intracellular Ca 2+ oscillations, and this induces phenotypic and genotypic changes in these cells. We then sought to examine the regenerative capacity of pediatric CPCs after conditioning with ES. In this study, we characterized the ES-induced changes in pediatric CPCs and showed they had a positive effect on the regenerative potential of these cells. ES-treated CPCs resulted in improved RV function following delivery compared with untreated CPCs in a juvenile rat model of right ventricular HF. Analysis of Ca 2+ handling in CPCs after chronic ES showed that these cells do not develop Ca 2+ transients or contractility similar to adult myocytes, and likely do not directly contribute to the contractility of the heart after injection. To determine if the effects were due to paracrine signaling, we tested the ability of conditioned media from these cells to regulate the function of failing cardiac myocytes. Isolated failing myocytes treated with conditioned media from CPCs showed improved Ca 2+ handling and contractility compared to untreated controls. Our data suggest that ES represents a novel treatment to enhance the therapeutic potential of pediatric CPCs, and the means of action of the modified cells is in part through a paracrine effect on resident cardiomyocytes.