Zhang Y, Zhou S, Hu J M, Chen H, Liu D, Li M, Guo Y, Fan L P, Li L Y, Liu Y G, Zhao M
Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Key Laboratory of Inflammatory and Immune Disease, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Transplant Proc. 2018 Dec;50(10):3873-3880. doi: 10.1016/j.transproceed.2018.04.063. Epub 2018 May 4.
Renal transplantation is currently the most effective treatment for end-stage kidney diseases, and acute allograft rejection is well treated with high dose prednisolone and immunosuppressive agents, but long-term use of immunosuppressants will be detrimental to the long-term survival of the transplanted kidney and will have many side effects on the human body. Thus, a local and alloantigen-specific immunological tolerance may be a promising approach to improving kidney transplantation. The aim of this study is to examine the therapeutic potential of transforming bone marrow-derived mesenchymal stem cells (BMSCs) pretreated with erythropoietin (EPO) in inducing immunosuppression in renal grafts after transplantation. The immunity suppression effects were tested, focusing on the decrease of serum creatinine and the cells' ability to regulate the expression of the cytokines associated with acute rejection. Our findings demonstrate that a transfusion of BMSCs pretreated with EPO (EPO-BMSCs) can produce an immunosuppressive effect and reduce the occurrence of acute rejection. Their reciprocal effects on the induction and function of regulatory T cells (Tregs) resulted in the balance of IFN-γ/IL-4 and improved immunosuppressive effects in local kidney grafts. Our data also suggest that the acute rejection microenvironment had a directional chemotactic effect on BMSCs, which is related to the upregulation of CXCR4, and could be further enhanced by EPO treatment. Thus, transfusion of EPO-BMSCs can induce a greater local immunosuppressive effect in renal grafts after transplantation compared with untreated BMSCs. Therefore, transplantation with EPO-BMSCs can be a novel and effective approach to lower the acute rejection ratio following transplantation.
肾移植是目前治疗终末期肾病最有效的方法，高剂量泼尼松龙和免疫抑制剂能有效治疗急性移植肾排斥反应，但长期使用免疫抑制剂会对移植肾的长期存活产生不利影响，且会对人体产生诸多副作用。因此，局部和同种异体抗原特异性免疫耐受可能是改善肾移植的一种有前景的方法。本研究的目的是检测经促红细胞生成素（EPO）预处理的骨髓间充质干细胞（BMSCs）在诱导移植后肾移植免疫抑制方面的治疗潜力。测试了免疫抑制效果，重点关注血清肌酐的降低以及细胞调节与急性排斥相关细胞因子表达的能力。我们的研究结果表明，输注经EPO预处理的BMSCs（EPO-BMSCs）可产生免疫抑制作用并减少急性排斥反应的发生。它们对调节性T细胞（Tregs）的诱导和功能的相互作用导致IFN-γ/IL-4平衡，并改善了局部肾移植中的免疫抑制效果。我们的数据还表明，急性排斥微环境对BMSCs具有定向趋化作用，这与CXCR4的上调有关，并且EPO处理可进一步增强这种作用。因此，与未处理的BMSCs相比，输注EPO-BMSCs可在移植后肾移植中诱导更大的局部免疫抑制作用。因此，EPO-BMSCs移植可能是降低移植后急性排斥率的一种新型有效方法。
