Abstract 11936: Comparative Assessment of Exogenous and Endogenous Cardiac Repair Using an Injectable Porcine Submucosa-Extracellular Matrix in a Myocardial Scar Model
Background: We examined possible effects and mechanisms involved in cardiac remodeling and vasculomyogenesis after injection of a clinically relevant, porcine-derived small intestinal submucosa-extracellular matrix (SIS-ECM) injectable material, with or without circulating angiogenic cells (CACs), in a mouse model of post-infarction myocardial scar.
Methods and Results: 9-10 week old female C57BL/6J mice (N=60) had their left anterior descending coronary artery ligated. Seven days later, animals were randomly allocated to receive echo-guided intramyocardial injections of PBS, male donor CACs (5 X 105 cells), SIS-ECM (total 20 μl), or SIS-ECM + CACs (5 X 105 cells). Repeat echocardiography, immunohistochemistry, and fluorescence in situ hybridization (FISH) were performed 28 days post-ligation. Baseline, post-ligation left ventricular ejection fraction (LVEF) was equivalent between groups. 21 days post-treatment, EF% improved in SIS-ECM+CACs (38±2%) and SIS-ECM (36±4%), compared to CACs alone (30±3%; p<0.1) and PBS groups (27± 1.5%). Masson’s trichrome stain was used to differentiate infarcted and viable myocardium. Infarction was reduced in SIS-ECM+CACs (37.76±2.5%; p<0.003) and SIS-ECM alone (34.86±3.1%;p<0.002), compared to CACs alone (46.05±6%; p<0.06) and PBS (62±6%)(p<0.002). Myocardial viability was increased in both matrix treated groups (≥65; p=0.002 vs. no matrix). Arteriolar density in peri-infarct regions was enhanced in both SIS-ECM treated groups (by ≥78±7%; p=0.03). More cardiomyocytes expressing β-catenin at intercellular adherens junctions were observed in SIS-ECM groups (≥19±1/FOV; p<0.005 vs. no matrix). An increase in GATA-4 positive cells was seen when SIS-ECM was combined with CACs (70±5/FOV; p=0.003). FISH on Y chromosome confirmed better retention of transplanted cells in the SIS-ECM + CACs group.
Conclusions: Intramyocardial delivery of SIS-ECM, a clinically relevant material, 7 days after myocardial infarction in a mouse model reduces infarct size, improves myocardial vessel density and function, and when combined with CACs, promotes transplanted cell retention and endogenous myocardial cellularity. These findings suggest a possible role for SIS-ECM in therapeutic cardiac regeneration.
- © 2013 by American Heart Association, Inc.