Abstract 13768: Intracoronary Infusion of Bone Marrow-Derived Mesenchymal Stromal Cells Expressing Heme Oxygenase-1 to Prevent Reperfusion Injury in Porcine Model of Myocardial Infarction
Combination of mesenchymal stromal cells (MSC) with antioxidative, antiapoptotic and proangiogenic enzyme heme oxygenase-1 (HO-1) is a novel approach for prevention of reperfusion injury in acute MI.
Aim was to evaluate the effects of intracoronary infusion of bone marrow (BM)-derived MSC overexpressing HO-1 administered immediately before reperfusion in porcine model of MI with regard to reduction of the infarct area (IA), improvement of left ventricular ejection fraction (LVEF), LV remodeling, diastolic function and expression of inflammation-related genes.
Methods: MSC were isolated from porcine BM and transduced 48 h before infusion with 50 MOI/cell of adenoviruses with HO-1 or GFP genes. MI was produced by 60-minutes inflation of OTW balloon catheter located in medial LAD in 27 domestic pigs. Prior to reperfusion animals were randomized to receive either HO-1-MSC, unmodified MSC, GFP+ MSC or placebo (normal saline) by slow infusion through the OTW catheter distally to the occlusion. Echocardiography was done before procedure, 30 min. after the reperfusion and 14 days later.
Results: Administration of HO-1 MSC improved LVEF after reperfusion significantly more than unmodified MSC. After 14 days there was a trend towards superiority of HO-1-MSC, however both types of MSC were comparably effective vs. placebo. There was no effect of cells on LV remodeling and diastolic function. Both types of MSC significantly reduced the infarct size. Expression of HIF-1 was significantly lower in the infarct border zone in pigs treated with cells than in placebo group. GFP-positive cells expressing PCNA were localized in the endothelium within the infarct border zone.
Conclusion: Intracoronary infusion of MSC prior to reperfusion reduced the infarct size and improved LV contractility and there was a trend towards more effective prevention of reperfusion injury in animals receiving MSC expressing HO-1. Proliferating donor MSC were identified within recipients endothelium.
- © 2011 by American Heart Association, Inc.