Mesenchymal stem cells from human amniotic membrane differentiate into cardiomyocytes and endothelial-like cells without improving cardiac function after surgical administration in rat model of chronic heart failure

Abstract

Introduction: Human amnion-derived mesenchymal stem cells (hAMSCs) have been used in the treatment of acute myocardial infarction. In the current study, we investigated the efficacy of hAMSCs for the treatment of chronic model of myocardial ischemia and heart failure (HF) in rats. Methods: Male Wistar rats weighing between 250 to 350 g were randomized into three groups: sham, HF control and HF+hAMSCs. For HF induction, animals were anesthetized and underwent left anterior descending artery ligation. In HF+hAMSCs group, 2×106 cells were injected into the left ventricular muscle four weeks post ischemia in the border zone of the ischemic area. Cardiac function was studied using echocardiography. Masson’s trichrome staining was used for studying tissue fibrosis. Cells were transduced with green fluorescent protein (GFP) coding lentiviral vector. Immunohistochemistry was used for detecting GFP, vascular-endothelial growth factor (VEGF) and troponin T markers in the tissue sections. Results: Assessment of the cardiac function revealed no improvement in the myocardial function compared to the control HF group. Moreover, tissue fibrosis was similar in two groups. Immunohistochemical study revealed the homing of the injected hAMSCs to the myocardium. Cells were stained positive for VEGF and troponin T markers. Conclusion: injection of hAMSCs 4 weeks after ischemia does not improve cardiac function and cardiac muscle fibrosis, although the cells show markers of differentiation into vascular endothelial cells and cardiomyocytes. In sum, it appears that hAMSCs are effective in the early phases of myocardial ischemia and does not offer a significant advantage in patients with chronic HF.

Keywords

• mesenchymal stromal cells
• chronic heart failure
• amnion