Quantitative hybrid cardiac [18F]FDG-PET-MRI images for assessment of cardiac repair by pre-conditioned cardiosphere derived cells

Abstract Cardiosphere-derived cells (CDC) are progenitor cells derived from heart tissue and have shown promising results in preclinical models. APOSEC, the secretome of irradiated peripheral blood mononuclear cells, has decreased infarct size in acute and chronic experimental myocardial infarction. We enhanced the effect of CDCs with APOSEC preconditioning (apoCDC), and investigated the reparative effect in a translational pig model of reperfused MI. Supernatants of CDCs assessed by proteomic analysis revealed reduced production of extracellular matrix proteins after in vitro APOSEC pre-conditioning. In a porcine model of catheter-based reperfused anterior acute MI, CDCs with (apoCDC, n=8) or without APOSEC-preconditioning (CDC, n=6) were infused intracoronary 15 min after the start of reperfusion. Untreated AMI animals (n=7) and sham procedures (n=5) functioned as controls. [18F]FDG-PET-MRI with late enhancement after one month showed reduced scar volume, and lower transmurality of infarcted area in CDC and apoCDC compared to AMI controls. Segmental quantitative PET images displayed indicated more residual viability in apoCDC. LV ejection fraction was improved non-significantly to 45.8±8.6 % for apoCDC and 43.5±7.1 % for CDCs compared to 38.5±4.4 % for untreated AMI. Quantitative hybrid [18F]FDG-PET-MRI demonstrated improved metabolic and functional recovery after CDC administration, while apoCDCs induced preservation of viability of the infarcted area.