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, 2×10 6 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.