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

Abstract

Although mesenchymal stem cells (MSC) 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 Ca2+ 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 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 Ca2+, intracellular Ca2+ rise and decay rate, which were reconciled by MSC. MSC therapy attenuated MI-induced apoptosis and decreased angiogenesis but not myocardial fibrosis in 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.

Restoration of Heart Function Using Transplantation of Human Umbilical Cord Matrix-Derived Cardiomyocytes and Vascular Endothelial Growth Factor

“…The achieved data indicates that intramyocardial injection of dhUCM cells combined with VEGF improves left ventricular function, enhances angiogenesis and attenuates fibrosis tissue in infarcted myocardium eight weeks after MI. Recent studies in the field ofcell therapy have shown new therapeutic potentials in the treatment of cardiac disease [27]. Previous studies had shown that various stem cell resources such as; bone marrow (BM-MSCs) [28], Embryonic (ESCs) [29], adipose tissue (ADCs) [12,30], cardiac (CSCs) [31] and umbilical cord blood stem cells (UCBSCs) [32] have beneficial effects on the restoration of cardiac function after MI, but practical application of these sources is limited.…”

“…The sections underwent trichromemasson staining for the evaluation of the amount of fibrosis tissue using MATLAB software (Mathworks Inc., Natick, MA, USA). Vascular density and fibrosis tissue of myocardium have been quantified as previously described in previous studies [27,28].…”

Stem cell therapy for cardiovascular disease: the demise of alchemy and rise of pharmacology

“…Intramyocardial injection of ex vivo expanded MSCs to the infarcted heart, immediately or shortly following MI, improves cardiac recovery (Imanishi et al, 2008;Chacko et al, 2009;Li et al, 2010). Besides being capable of transdifferentiation, MSCs act as potent activators of angiogenesis through the release of angiogenic factors.…”

Dual-modal tracking of transplanted mesenchymal stem cells after myocardial infarction

“…Intravenous infusion and intramyocardial injection are the current predominant stem cell delivery routes for the infarcted heart of small animals. 13,14 Cell delivery by intravenous infusion has the advantage of simple administration, but Carr et al reported it could not ameliorate cardiac dysfunction. 15 In contrast, the intramyocardial route has the associated disadvantages of being a highly invasive operation and requires a limited dose.…”