Prompt bone marrow-derived mesenchymal stem cell therapy enables early porcine heart function recovery from acute myocardial infarction

Abstract

Impact of early bone marrow-derived mesenchymal stem cell (BMDMSC) implantation on left ventricular (LV) function after AMI was studied. Twelve mini-pigs were equally divided into placebo (AMI through left coronary artery ligation) and cell-treated groups [BMDMSCs (3.0 × 107) implanted into infarct area (IA)] with myocardium harvested by post-AMI day 90. Six healthy animals served as controls. On post-AMI day 90, magnetic resonance imaging showed a lower LV ejection fraction but higher LV dimensions in the placebo group (P < 0.003) that also had increased IAs but reduced wall thickness (P < 0.005). Pro-apoptotic gene expressions (Bax, caspase-3) and apoptotic nucleus number in IAs and peri-IAs were highest in the placebo group (P < 0.001). Inflammatory biomarker expressions (MMP-9, oxidized protein, CD40+ cells) were highest, whereas those of angiogenesis (VEGF, CD31+ cells, SDF-1α, CXCR4) and myocardium-preservation (connexin43, troponin-I, cytochrome- C) were lowest in the placebo group (P < 0.01). BMDMSC implantation preserved LV function and alleviated remodeling at post-AMI day 90.