Abstract 16466: Comparison of Cardiac Engraftment With Two Catheter-Based Delivery Methods: Catheter-Mediated Intramyocardial Delivery Outperforms Intracoronary Delivery of Cardiosphere-Derived Cells in Porcine Ischemic Cardiomyopahty
Background: Dosage-optimized intracoronary (IC) and direct intramyocardial (IM) delivery of cardiosphere-derived cells (CDCs) have both been demonstrated to be safe and effective in porcine ischemic cardiomyopathy. However, IC and IM delivery of heart-derived stem cells have never been compared head-to-head and quantitatively in a clinically-relevant large animal model. This study was designed to systematically compare CDCs engraftment rates after IC, or catheter-mediated IM delivery, in a porcine model of ischemic cardiomyopathy.
Methods and results: Myocardial infarction was induced in mini-pigs (n=7) by balloon occlusion of the mid-LAD for 2.5h. 2-4 weeks after MI, mini-pigs received, by prior random assignment, ∼300,000/kg luciferase-labeled allogeneic CDCs, delivered by: 1) IC infusion in the mid-LAD, via an over-the-wire balloon catheter under stop-flow conditions (n=3), or 2) MYOSTARTM catheter-mediated IM injection into the peri-infarct zone following electromechanical mapping of the left ventricle utilizing NOGA® XP cardiac navigation technology (n=4). Mini-pigs were sacrificed 24h post cell delivery, the heart was explanted and cardiac engraftment was measured with the ex vivo luciferase assay. In the IC infusion group, serum troponin I was measured 24h post infusion in order to detect possible myocardial injury due to cell-related microembolization. Percent engraftment 24h post transplantation was 13.3±4.0 % after catheter-guided IM delivery and 4.26±2.2 % after IC infusion (p=0.02). Troponin I levels 24h after CDCs infusion were < 0.05ng/ml, indicating no cell-related myocardial injury. No deaths were observed in either group during the peri-procedural period.
Conclusions: Delivery of cardiosphere-derived cells by two distinct minimally-invasive percutaneous approaches is safe and feasible. However, guided catheter-based intramyocardial injection of CDCs is superior to intracoronary infusion in terms of short-term cardiac engraftment. Although IC delivery of CDCs is safe and effective in reducing infarct size, attenuating remodeling and improving function, the present results give good reason to predict superior benefits with catheter-mediated IM injection.
- Cardiac regeneration
- Stem cell therapy
- Ischemic heart disease
- Interventional studies
- Cardiovascular therapeutics
- © 2011 by American Heart Association, Inc.