Wang Feng, Yao Guanping, Pan Sisi, Mao Xin, Zhao Xu, Li Chuntian, Hong Zheng, Liang Guiyou, Yu Limei, Hu Xuanyi, Peng Wanfu
Department of Clinical Medical College, Guizhou Medical University, Guiyang, China.
Department of Cardiac Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, China.
J Thorac Dis. 2021 Aug;13(8):5064-5076. doi: 10.21037/jtd-21-1034.
Immune rejection of heart transplantation has been regarded as the biggest challenge encountered by a patient suffering from end-stage heart disease. The transplantation of human amnion-derived mesenchymal stem cells (hAD-MSCs) has exhibited promising application prospects in organ transplantation. However, its persistent unsatisfactory tolerance has limited the widespread application of this technology. We aim to investigate the role of tumor necrosis factor-α-induced protein-8 like-2 ()-mediated hAD-MSCs in immune tolerance in heart transplantation and its molecular regulatory mechanisms.
This project detected the effect of on immune tolerance by constructing an allogeneic heart transplantation mouse model through which -overexpressed hAD-MSCs were injected into recipients. The fluorescence distribution of -hAD-MSCs in mice was observed by a small animal imaging system. Pathological changes of the transplanted heart were detected by hematoxylin and eosin (HE) staining. Flow cytometry was performed to detect the content of cardiac lymphocytes. The expression of immune-induced related factors was measured by quantitative real-time PCR (qRT-PCR) and western blot assays.
-hAD-MSCs protected myocardial tissue structures, reduced the spleen and thymus indexes in recipient mice, minimized the content of cardiac lymphocytes, reduced expressions of , , and -, and elevated expressions of both and -, markedly improving the survival time and survival rates of recipient mice.
-hAD-MSCs induce immune tolerance and improve the survival rates of allogeneic heart transplantation in mice. This study is expected to offer an ideal source and target of cells for organ transplantation.
心脏移植的免疫排斥一直被视为终末期心脏病患者面临的最大挑战。人羊膜间充质干细胞（hAD-MSCs）移植在器官移植中展现出了广阔的应用前景。然而，其耐受性一直不尽人意，限制了该技术的广泛应用。我们旨在研究肿瘤坏死因子-α诱导蛋白-8样2（）介导的hAD-MSCs在心脏移植免疫耐受中的作用及其分子调控机制。
本项目通过构建同种异体心脏移植小鼠模型，将过表达的hAD-MSCs注入受体，检测其对免疫耐受的影响。利用小动物成像系统观察-hAD-MSCs在小鼠体内的荧光分布。通过苏木精-伊红（HE）染色检测移植心脏的病理变化。采用流式细胞术检测心脏淋巴细胞含量。通过定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测免疫诱导相关因子的表达。
-hAD-MSCs保护心肌组织结构，降低受体小鼠的脾脏和胸腺指数，减少心脏淋巴细胞含量，降低、和-的表达，提高和-的表达，显著延长受体小鼠的存活时间并提高其存活率。
-hAD-MSCs可诱导免疫耐受并提高小鼠同种异体心脏移植的存活率。本研究有望为器官移植提供理想的细胞来源和靶点。
