Gorjipour Fazel, Hosseini-Gohari Ladan, Alizadeh Ghavidel Alireza, Hajimiresmaiel Seyed Javad, Naderi Nasim, Darbandi Azar Amir, Pazoki-Toroudi Hamidreza
Cellular and Molecular Research center, Iran University of Medical Sciences, Tehran, Iran.
Rajaie Cardiovascular and Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
J Cardiovasc Thorac Res. 2019;11(1):35-42. doi: 10.15171/jcvtr.2019.06. Epub 2019 Feb 25.
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. 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. 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. 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.
人羊膜间充质干细胞（hAMSCs）已被用于治疗急性心肌梗死。在本研究中，我们调查了hAMSCs对大鼠慢性心肌缺血和心力衰竭（HF）模型的治疗效果。将体重在250至350克之间的雄性Wistar大鼠随机分为三组：假手术组、HF对照组和HF+hAMSCs组。为诱导HF，动物麻醉后进行左前降支动脉结扎。在HF+hAMSCs组中，在缺血四周后将2×106个细胞注射到缺血区域边缘区的左心室肌中。使用超声心动图研究心脏功能。采用Masson三色染色法研究组织纤维化。用编码绿色荧光蛋白（GFP）的慢病毒载体转导细胞。免疫组织化学用于检测组织切片中的GFP、血管内皮生长因子（VEGF）和肌钙蛋白T标记物。心脏功能评估显示，与HF对照组相比，心肌功能没有改善。此外，两组的组织纤维化情况相似。免疫组织化学研究显示注射的hAMSCs归巢至心肌。细胞VEGF和肌钙蛋白T标记物染色呈阳性。尽管细胞显示出向血管内皮细胞和心肌细胞分化的标记物，但在缺血四周后注射hAMSCs并不能改善心脏功能和心肌纤维化。总之，hAMSCs似乎在心肌缺血的早期阶段有效，而对慢性HF患者没有显著优势。
