Abstract 16: Enhancing Myocardial Repair With CardioChimeras

Abstract

Dual cell transplantation of cardiac progenitor cells (CPCs) and mesenchymal stem cells (MSCs) after infarction enhances myocardial repair and performance in large animal models relative to delivery of either cell population individually. However, a single stem cell to support both direct and indirect mechanisms of myocardial repair has yet to be identified. CardioChimeras (CCs), a progenitor cell formed by fusion between CPCs and MSCs were analysed for reparative potential after myocardial infarction (MI) relative to individual parents cell or combined parent cell delivery. Two representative CCs, CardioChimera 1 (CC1) and CardioChimera 2 (CC2) were used for this study. CC1 and CC2 improved left ventricular anterior wall thickness (AWT) at 4 weeks, but only CC1 treatment preserved AWT at 18 weeks relative to no cell treatment (PBS). Ejection fraction was enhanced at 6 weeks post injury in CC1 and CC2 groups, which was maintained in CC1, CC2 and CPC + MSC combined groups up to 18 weeks. Infarct size was decreased by 5% in CC1 and CC2 hearts, whereas CPC + MSC and CPC parent groups remained unchanged when comparing 4 to 12 week change in scar size. MSC and PBS groups displayed marked increases in infarct size (10-15%). CC1 and CC2 showed enhanced engraftment potential by 3-fold relative to CPC + MSC and CPC hearts. In contrast, MSCs were detected at low levels (0.04%). CC1 and CC2 discovered within the myocardium expressed early commitment marker cardiac troponin T relative to controls. CC1 and CC2 treatment increased capillary density within the infarct, indicating that cell persistence facilitates paracrine mediated vasculature stabilization and/or formation. CCs merge the application of distinct cells into a single entity for cellular therapeutic intervention in the progression of heart failure. CCs represent a tractable cellular system that improves upon combinatorial cell therapy approaches and supports myocardial regeneration.