Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: Short- and long-term effects

Abstract

Background-Mesenchymal stem cells (MSCs) have the potential to replace infarct scar, but the long-term effects are unknown. We studied short- and long-term effects of MSC transplantation on left ventricular (LV) function in a rat myocardial infarction model. Methods and Results-Saline (n = 46) or MSCs labeled with 1,1′-dioctadecyl-3,3,3′3′- testramethylindocarbocyanine perchlorate (DiI; n = 49, 2 × 106 cells each) were injected into the scar of a 1-week-old myocardial infarction in Fischer rats. The presence and differentiation of engrafted cells and their effect on LV ejection fraction was assessed. At 4 weeks, LV stroke volume was significantly greater in the MSC-treated group (145 ± 9 μL) than in the saline group (122 ± 3 μL, P = 0.032), and LV ejection fraction was significantly greater in MSC-treated animals (43.8 ± 1.0%) than in the saline group (38.8 ± 1.1%, P = 0.0027). However, at 6 months, these benefits of MSC treatment were lost. DiI-positive cells were observed in the MSC group at 2 weeks and at 3 and 6 months. Expression of the muscle-specific markers α-actinin, myosin heavy chain, phospholamban, and tropomyosin was not observed at 2 weeks in DiI-positive cells. At 3 and 6 months, the DiI-positive cells were observed to express the above muscle-specific markers, but they did not fully evolve into an adult cardiac phenotype. Some of the DiI-positive cells expressed von Willebrand factor. Conclusions-Allogeneic MSCs survive in infarcted myocardium as long as 6 months and express markers that suggest muscle and endothelium phenotypes. MSCs improved global LV function at 4 weeks; however, this benefit was transient, which suggests a possible early paracrine effect. © 2005 American Heart Association, Inc.