Abstract 19030: Intramyocardial Injection of Autologous Cardiospheres or Cardiosphere-Derived Cells Preserves Function and Minimizes Adverse Ventricular Remodeling in Pigs With Heart Failure Post-Myocardial Infarction
Background: Intracoronary administration of cardiosphere-derived cells (CDCs) has been demonstrated to reduce infarct size and improve hemodynamic indices in the mini-pig model, but intramyocardial injection of CDCs or their 3-dimensional precursors, cardiospheres (CSps), has not been assessed in large animals. We tested the safety and efficacy of direct injection of CDCs and CSps for cellular cardiomyoplasty in a mini-pig model of heart failure post-myocardial infarction (MI).
Methods: Autologous CSps or CDCs grown from endomyocardial biopsies were injected via thoracotomy four weeks post-anteroseptal MI. Engraftment optimization with luciferase-labeled CDCs guided the choice of cell dose (0.5M cells/site) and target tissue (20 peri-infarct sites). Pigs were randomized to placebo (n=11), cardiospheres (n=8) or CDCs (n=10). Functional data were acquired before injection and again 8 weeks later, after which organs were harvested for histopathology.
Results: Beyond the immediate perioperative period, all animals survived to protocol completion. Ejection fraction was equivalent at baseline but, at 8 weeks, was higher than placebo in both of the cell-treated groups (LVEF: 36.2±5.5% [placebo] vs 43.0±5.7% [CDCs] vs 43.3±6.2% [CSps], ANOVA p=0.01; placebo vs CDCs p=0.007; placebo vs CSps p=0.02). Echocardiographic (apical septum thickening: 10.2±7.8% [placebo] vs 22.9±15.5% [CDCs] vs 38.7±25.7% [CSps], p=0.008) and hemodynamic (Emax: 1.03±0.29 [placebo] vs 1.66±0.45 [CDCs] vs 3.16±1.32mmHg/ml [CSps], p=0.002) indices of efficacy improved disproportionately with CSps; likewise, adverse remodeling was more attenuated with CSps than with CDCs (delta end-diastolic volume: +0.7±8.5 [CSps] vs +20.8±10.1ml [CDCs], p=0.02; delta end diastolic pressure: -5.8±4.5 [CSps] vs +1.5±4.4mmHg [CDCs], p=0.01). Provocative electrophysiologic testing showed no differences among groups, and no tumors were found.
Conclusion: Dosage-optimized direct injection of CSps or CDCs is safe and effective in preserving ventricular function in porcine ischemic cardiomyopathy. While CDCs and CSps have equivalent effects on LVEF, cardiospheres are superior in improving hemodynamics and regional function, and in attenuating ventricular remodeling.
- © 2010 by American Heart Association, Inc.