Effects of intracoronary delivery of allogenic bone marrow-derived stem cells expressing heme oxygenase-1 on myocardial reperfusion injury

Abstract

Heme oxygenase-1 (HO-1) decreases apoptosis, inflammation and oxidative stress. The aim of the study was to investigate the effects of intracoronary infusion of allogenic bone marrow cells (BMC) overexpressing HO-1 in the porcine model of myocardial infarction (MI). MI was produced by balloon occlusion of a coronary artery. BMC were transduced with adenoviruses encoding for HO-1 (HO-1 BMC) or GFP (GFP-BMC) genes. Prior to reperfusion animals received HO-1 BMC, control BMC (unmodified or GFP-BMC) or placebo. Left ventricular (LV) ejection fraction (EF), shortening fraction (SF), end-systolic and end-diastolic diameters (EDD, ESD) were assessed by echocardiography before, 30 minutes (min) and 14 days after reperfusion. BMC significantly improved LVEF and SF early (30 min) after reperfusion as well as after 14 days. Early after reperfusion HO-1 BMC were significantly more effective than control BMC, but after 14 days, there were no differences. There were no effect of cells on LV remodelling and diastolic function. Both HO-1 BMC and control BMC significantly reduced the infarct size vs. placebo (17.2 ± 2.7 and 18.8 ± 2.5, respectively, vs. 27.5 ± 5.1, p= 0.02) in histomorphometry. HO-1-positive donor BMC were detected in the infarct border area in pigs receiving HO-1-cells. No significant differences in expression of inflammatory genes (SDF-1, TNF-α, IL-6, miR21, miR29a and miR133a) in the myocardium were found. In conclusion, intracoronary delivery of allogeneic BMC immediately prior to reperfusion improved the LVEF and reduced the infarct size. HO-1 BMC were not superior to control cells after 14 days, however, produced faster recovery of LVEF. Transplanted cells survived in the peri-infarct zone.