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 (nϭ46) or MSCs labeled with 1,1Ј-dioctadecyl-3,3,3Ј3Ј-testramethylindocarbocyanine perchlorate (DiI; nϭ49, 2ϫ10 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 (145Ϯ9 L) than in the saline group (122Ϯ3 L, Pϭ0.032), and LV ejection fraction was significantly greater in MSC-treated animals (43.8Ϯ1.0%) than in the saline group (38.8Ϯ1.1%, Pϭ0.0027). 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 ␣-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

This study shows that collagen injection thickens an infarct scar and improves LV stroke volume and ejection fraction, and prevents paradoxical systolic bulging after myocardial infarction.