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人羊膜间充质干细胞与改良的 PGS-co-PCL 膜联合应用于心肌缺血再灌注损伤的实验模型。

Combined Application of Human Amniotic Membrane Mesenchymal Stem Cells and a Modified PGS-co-PCL Film in an Experimental Model of Myocardial Ischemia-Reperfusion Injury.

机构信息

Department of Molecular and Cellular Sciences, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

出版信息

Appl Biochem Biotechnol. 2023 Dec;195(12):7502-7519. doi: 10.1007/s12010-023-04446-5. Epub 2023 Apr 3.

DOI:10.1007/s12010-023-04446-5
PMID:37010740
Abstract

According to the World Health Organization (WHO), about 3.9 million people die annually of ischemic heart disease (IHD). Several clinical trials have shown that stem cell therapy is a promising therapeutic approach to IHD. Human amniotic membrane mesenchymal stem cells (hAMSCs) positively affect the repair of myocardial ischemia-reperfusion (MI/R) injury by stimulating endogenous repair mechanisms. The differentiated hAMSCs with and without modified PGS-co-PCL film were applied in the myocardium. MI/R injury was induced by ligating the left anterior descending artery in 48 male Wistar rats. The rats were divided into four groups, (n = 12) animals: heart failure (HF) as the control group, HF + MSCs, HF + MSCs + film, and HF + film. Echocardiography was performed 2 and 4 weeks after MI/R injury moreover the expression of the VEGF protein was assessed in the rat heart tissue via immunohistochemistry. In vitro, our result shows fantastic cell survival when seeded on film. In vivo, the left ventricle ejection fraction (LEVD), fractional shortening (FS), end-diastolic (EDV), and stroke volume (SV) have been increased and systolic volumes decreased in all treatment groups in comparison with control. Although combination therapy has a more positive effect on hemodynamic parameters, there is no significant difference between HF + MSCs + film with other treatment groups. Also, In the IHC assay, expression of the VEGF protein significantly increased in all intervention groups. The implantation of MSCs and the modified film significantly enhanced the cardiac functional outcome; in this regard, enhancement in cell survival and VEGF expression are involved as underlying mechanisms in which cardiac film and MSCs exert a beneficial effect.

摘要

根据世界卫生组织(WHO)的数据,每年约有 390 万人死于缺血性心脏病(IHD)。几项临床试验表明,干细胞疗法是治疗缺血性心脏病的一种很有前途的方法。人羊膜间充质干细胞(hAMSCs)通过刺激内源性修复机制,积极影响心肌缺血再灌注(MI/R)损伤的修复。将未经修饰和经过 PGS-co-PCL 膜修饰的分化 hAMSCs 应用于心肌。通过结扎雄性 Wistar 大鼠的左前降支诱导 MI/R 损伤。将大鼠分为四组(n=12):心力衰竭(HF)作为对照组,HF+MSCs、HF+MSCs+膜和 HF+膜。在 MI/R 损伤后 2 周和 4 周进行超声心动图检查,并通过免疫组织化学评估大鼠心脏组织中 VEGF 蛋白的表达。体外实验结果显示,细胞在膜上的存活率很高。体内实验结果显示,与对照组相比,所有治疗组的左心室射血分数(LEVD)、缩短分数(FS)、舒张末期(EDV)和每搏量(SV)均增加,收缩量减少。尽管联合治疗对血液动力学参数有更积极的影响,但 HF+MSCs+膜与其他治疗组之间没有显著差异。此外,在免疫组织化学检测中,所有干预组的 VEGF 蛋白表达均显著增加。MSCs 和改良膜的植入显著增强了心脏功能;在这方面,细胞存活和 VEGF 表达的增强是涉及心脏膜和 MSCs 发挥有益作用的潜在机制。

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