间充质干细胞
移植
医学
免疫系统
免疫耐受
流式细胞术
干细胞
免疫学
癌症研究
病理
生物
内科学
细胞生物学
作者
Feng Wang,Guanping Yao,Sisi Pan,Xin Mao,Xiaolan Zhao,Chuntian Li,Hong Zheng,Guiyou Liang,Limei Yu,Xuan-Yi Hu,Wanfu Peng
出处
期刊:Journal of Thoracic Disease
[AME Publishing Company]
日期:2021-08-01
卷期号:13 (8): 5064-5076
摘要
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 (TIPE2)-mediated hAD-MSCs in immune tolerance in heart transplantation and its molecular regulatory mechanisms.This project detected the effect of TIPE2 on immune tolerance by constructing an allogeneic heart transplantation mouse model through which TIPE2-overexpressed hAD-MSCs were injected into recipients. The fluorescence distribution of TIPE2-hAD-MSCs in mice was observed by a small animal in vivo 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.TIPE2-hAD-MSCs protected myocardial tissue structures, reduced the spleen and thymus indexes in recipient mice, minimized the content of cardiac lymphocytes, reduced expressions of ERK, p38, and IFN-γ, and elevated expressions of both IL-10 and TGF-β, markedly improving the survival time and survival rates of recipient mice.TIPE2-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.
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