Effects of cell-basedgene therapy on infarct size and ventricular function in an ovine model of acute myocardial infarction

HNATIUK A; GING ONG S,; OLEA D; LOCATELLI P; GIMÉNEZ CS; WU J; CROTTOGINI A

Bordeaux

Congreso; ISHR European Section Annual Meeting 2015; 2015

International Society for Heart Research

Background:Acute myocardial infarction (AMI) remains the major cause of death worldwide. The severity of heart failure is associated with the initial scar size.is associated with severity of heart failure. Hypoxia inducible factor 1-α (HIF1-α) is a transcription factor that has been shown to mediate cardioprotection. In this study, we seek to investigate the cardioprotective effects of bone marrow mesenchymal stem cells (BMMSCs) transfected with a non-viralminicircle vector encoding a mutant form of HIF1-α (mHIF1-α: P402A/P564G) resistant to normoxic degradation in an ovine model of AMI..Methods and results: Sheep with coronary ligation were injected intramyocardiallywith mHIF1-α-transfected BMMSCs (BMMSC-mHIF, n=6), naïve BMMSCs (BMMSC, n=6) or PBS (placebo, n=6). One and 60 days post-AMI, infarct size and ejection fraction (EF) were measured by cardiac magnetic resonance. At day 60, infarct size was reduced by 71.7±3.1% in BMMSC-mHIF (from 9.6±0.7 to 2.7±0.3 ml; p