Intra-myocardial delivery of mesenchymal stem cells ameliorates left ventricular and cardiomyocyte contractile dysfunction following myocardial infarction.

Abstract Although mesenchymal stem cells (MSCs) transplantation may improve the overall heart function, the heterogeneity of myocardial cells makes it difficult to determine the nature of cells benefited from transplantation. This study evaluated the effect of intra-myocardial MSC transplantation on myocardial function following MI. Enhanced green fluorescent protein (EGFP)-expressing donor MSCs from C57BL/6-Tg (UBC-GFP) 30Scha/J mice were transplanted into LV free wall in the region bordering an infarct in C57 recipient mice following ligation of left main coronary artery (MI + MSC group). Ten days after MI, LV function was assessed using echocardiography. Cardiomyocyte contractility and intracellular Ca 2+ transients were measured in cells from the area-at-risk surrounding the infarct scar. The EGFP donor cells were traced in the MSC recipient mice using fluorescence microscopy. TUNEL, H&E and Masson trichrome staining were used to assess apoptosis, angiogenesis and myocardial fibrosis, respectively. MI dilated LV as evidenced by increased end-diastolic and end-systolic diameters. MI significantly reduced fractional shortening, cardiomyocyte peak shortening, and maximal velocity of shortening and relengthening, all of which were attenuated or abrogated by MSC therapy. MI also reduced resting intracellular Ca 2+ , intracellular Ca 2+ rise and decay rate, which were reconciled by MSC. MSC therapy attenuated MI-induced apoptosis and decreased angiogenesis but not myocardial fibrosis in the peri-infarct area. Taken together, our results demonstrated that MSC therapy significantly improved both LV and cardiomyocyte function possibly associated with its beneficial role in apoptosis and angiogenesis, indicating a key role for cardiomyocytes in stem cell tissue engineering.