人羊膜上皮细胞原位移植对大鼠急性心肌梗死后心功能和心室重构的改善作用

王钰莹; 方宁; 陈代雄; 余丽梅; 赵春华

doi:10.13201/j.issn.1001-1439.2014.02.022

人羊膜上皮细胞原位移植对大鼠急性心肌梗死后心功能和心室重构的改善作用

- 1. 遵义医学院附属医院贵州省细胞工程重点实验室(贵州遵义, 563003);
- 2. 中国医学科学院基础医学研究所组织工程研究中心
基金项目:
“重大新药创制”同科技重大专项课题 No:2009ZX09503-025)

贵州省科技厅计划发展项目 No:黔科合2003 JGy005)

贵州省科技厅公关项目 No:黔科合SZ字[2009]3017)

详细信息

通讯作者: 陈代雄,E-mail:cellgene@163.com

中图分类号: R541.4

收稿日期: 2013-06-21

修回日期: 2013-11-23

Orthotopic transplanted human amniotic epithelial cells in improving left ventricular function and ventricular remodeling in rats with acute myocardial infarction

- 1. Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medcial College, Zunyi, Guizhou, 563003, China;
- 2. Tissue Engineering Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Science

More Information

Corresponding author: CHEN Daixiong, E-mail: cellgene@163.com

Received Date: 21 June 2013

Revised Date: 23 November 2013

摘要

摘要: 目的:研究人羊膜上皮细胞 (hAECs) 对急性心肌梗死 (AMI) 大鼠左心室功能和心室重构的影响及其在AMI区的分化。方法:结扎大鼠左冠状动脉前降支以建立AMI模型, 随机分为hAECs移植组 (14只)、模型组 (12只) 和假手术组 (12只)。胰酶消化分离hAECs, 采用流式细胞仪检测和免疫组织化学染色以鉴定其表型特征。成模后1周经心外膜移植2×10⁶ BrdU标记的hAECs, 于移植后不同时间采用超声心动图检查心功能变化, HE和Masson染色观察心肌重构变化, 免疫荧光双染色检测hAECs在AMI区的植活与分化。结果:①流式细胞仪检测显示第3代hAECs高表达CD29、CD166、CD73和CK19, 低表达或不表达CD34、CD45、CD44、CD80、CD86和HLA-DR;②hAECs移植后1、4和6周, 与模型组比较, hAECs移植组射血分数和左室短轴缩短率显著升高 (均P<0.01), 舒张期左室前壁厚度和收缩期左室前壁厚度明显增大 (均P<0.05), AMI区心肌纤维化程度明显减轻 (P<0.01);③hAECs移植后6周, AMI区可见BrdU标记的阳性细胞, 移植的hAECs向心肌样细胞分化, 连接蛋白-43、α-辅肌动蛋白和结蛋白表达阳性。结论:hAECs移植能改善AMI后心脏功能, 减缓心室重构, 在AMI区可分化为心肌样细胞。
- 心肌梗死 /
- 人羊膜上皮细胞 /
- 移植 /
- 心功能
Abstract: Objective: To investigate the effects of human amniotic epithelial cells (hAECs) transplantation on cardiac function and ventricular remodeling of rats with acute myocardial infarction (AMI) and observe the survival and differentiation of hAECs to cardiomyocytes in the AMI zone.Method: AMI models were made by left anterior descending artery ligation in male SD rats (200±20) g, and then randomly divided into hAECs transplanted group (n=14), model group (n=12) and sham operation group (n=12).The hAECs were isolated from the human amnion using trypsin digestion method, and then its phenotype was identified by flow cytometry and immunohistochemical staining.Seven days after the AMI, 2×10⁶ BrdUlabeled hAECs were injected into the myocardium at the border zone of the AMI.At 1, 4and 6week after transplantation, echocardiogram, histopathology, immunohistochemistry and immunofluorescence were performed to observe the changes of ventricular remodeling and cardiac function, as well as the survival and differentiation of hAECs in the AMI zone.Result: ①hAECs at passage 3highly expressed CD29, CD166, CD73and CK19;weakly expressed CD34, CD44, CD45, CD80, CD86and HLA-DR.②Transplantation of hAECs after all increased left ventricular ejection fraction, left ventricular fractional shorting, left ventricular anterolateral wall thickness at diastole, and left ventricular anterolateral wall thickness at systole, and decreased myocardial area (all P<0.05) significantly.③Six weeks after the transplantation, BrdU-labeled hAECs expressed cardiac-specific protein connexin-43, α-actinin and desmin in the AMI region.Conclusion: The hAECs transplantation can improve cardiac function and ventricular remodeling after AMI, and transplantated hAECs can differentiate into cardiomyocyte-like cells.
- myocardial infarction /
- human amniotic epithelial cells /
- transplantation /
- cardiac function

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