Abstract 17652: Dual Stem Cell Therapy Using Fetal Cardiac Progenitor Cells with EPCs Enhances Benefit in an Acute Myocardial Infarction Model
Stem cell therapy approaches with single cell types (e.g. autologous bone marrow mononuclear or allogeneic mesenchymal cells), have been demonstrated to produce partial short-term beneficial outcomes in myocardial and/or vascular repair/regeneration following MI. This study was undertaken to investigate whether dual cell transplantation using Isl-1+ cardiac progenitor cells (CPCs) in conjunction with CD90+/Thy1+ EPCs would be more effective than CPCs alone in attenuating ischemia-related damage following left anterior descending (LAD) coronary artery ligation. CPCs were isolated from E12 rat fetal hearts and expanded ex vivo. Characterization of isolated cells by immunofluorescence showed expression of cardiac precursor markers (Isl-1, Nkx2.5, and GATA4). CD90+/Thy1+ EPCs were isolated from bone marrow of adult male rats. Eight-week-old Sprague Dawley female rats underwent permanent LAD coronary ligation followed by intramyocardial injection (0.05ml) of either CPCs (3x106) (n=10), CPCs (3x106) + EPC (3x106) (n=10), or saline (n=10). Cells or saline were delivered trans-epicardially to the border zone immediately after LAD ligation. Left ventricular (LV) function was assessed by trans-thoracic echocardiography at 1 week (baseline) and 4 weeks post-MI after which rats were sacrificed and hearts processed for histological examination. In the saline group, we observed an increase in LV end-diastolic area from baseline to 4 weeks post-MI (0.33 ± 0.02 vs. 0.38 ± 0.08; P=0.03) and a decrease in E/A ratio (1.70 ± 0.54 vs. 1.27 ± 0.06, P=0.001) documenting deteriorating LV function. In the CPC group LV wall thinning was completely prevented (AWT, ASWT, PWT, P>0.05) as LV systolic and diastolic function were not significantly changed over time. In the CPC/EPC group we observed that LV wall thinning was also prevented but with this combined treatment LV function was increased (% FAC, 47.8 ± 4.1 vs. 62.2 ± 6.2, P=0.01). In summary, combination therapy using CPC plus EPCs shows greater efficacy than CPCs alone in post-MI myocardial recovery likely by supporting enhanced neovascularization, as well as, cardiomyocyte recovery/regeneration following acute ischemic injury
- © 2012 by American Heart Association, Inc.