Abstract 16214: Percutaneous Intra-myocardial Injection of Exosomes From Cardiosphere-derived Cells (CDCs) Halts Adverse Remodeling and Decreases Scar Size in Porcine Ischemic Cardiomyopathy
Background: Multiple lines of evidence indicate that the beneficial effects of CDCs in heart disease are mediated by exosomes. So far, no study has assessed the benefit of CDC-derived exosomes in a translationally-realistic large-animal model.
Objective: Exosomes are nanoscale particles, few of which may linger in the heart after routine intracoronary delivery. Previous work in rodents shows efficacy in myocardial infarction (MI) with intramyocardial injection. We therefore sought to evaluate the efficacy of trans-endocardial delivery of CDC-secreted exosomes using the NOGA MYOSTAR injection catheter in a porcine model of post-MI cardiomyopathy.
Methods: MI was induced in 7 mini-pigs by balloon occlusion of the mid-LAD for 2.5h, then the MI was allowed to heal for 4 weeks. At that point, and at the end of the study one month later, MRI was performed to measure LV volumes and ejection fraction (EF), scar mass and viable mass. Just after the first MRI, the left ventricle (LV) was mapped using a NOGA catheter to delineate infarcted, border and remote areas. After mapping, human CDC-secreted exosomes (7.5mg of exosome protein divided into 10-15 injections, n=4) or vehicle (n=3) were injected in the border zone (4-7 mV tip potentials).
Results: EF was identical in the two groups at baseline (38±4%). All pigs were successfully injected with exosomes or vehicle after comprehensive LV mapping. One month post-injection, EF was preserved in exosome-treated pigs but dramatically decreased in placebo-treated animals (ΔEF=-1.2±2.2% vs. -7.6±2.8%, p<0.02). LV adverse remodeling was attenuated in CDC-injected pigs (less increase in end-systolic and end-diastolic volumes, P=0.08 and P=0.03 respectively). Additionally, exosomes reduced scar mass (-1.6±0.6g vs. +1.2±0.5g, P=0.001) and scar size (P<0.05).
Conclusions: CDC-secreted exosomes halt adverse remodeling and decrease scar size when injected in the border zone using an injection catheter. This demonstration of safety and efficacy motivates testing of exosomes as cell-free therapeutic agents in humans.
Author Disclosures: R. Gallet: None. J. Dawkins: None. E. Simsolo: None. J. Valle: None. M. Kreke: None. R. Smith: None. L. Marbán: Employment; Significant; Capricor Inc.. Ownership Interest; Significant; Capricor Inc. E. Marbán: Employment; Significant; Capricor Inc.. Ownership Interest; Significant; Capricor Inc.. Consultant/Advisory Board; Significant; Capricor Inc..
- © 2015 by American Heart Association, Inc.