Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
Immunobiology. 2020 Sep;225(5):151994. doi: 10.1016/j.imbio.2020.151994. Epub 2020 Jul 31.
Although mesenchymal stem cells (MSCs) are regarded as immune-elusive and even immunosuppressive, recent evidence suggests that allogeneic immune response might is inevitable in the case of some lineages differentiated from MSCs. Regarding the importance of allogeneic IPCs and MSCs in pre-clinical and clinical studies, the present study aimed to investigate the possible changes in the immunogenicity of MSCs during the differentiation to IPCs in a murine model of allogeneic transplantation.
Two mouse strains, C57BL/6 (H2D) and BALB/c (H2D) were selected to establish an allogeneic cell transplantation model. Bone marrow MSCs were differentiated into IPCs and the expression of H2D, CD80, and Qa-2 molecules were evaluated via flowcytometry on MSCs and IPCs. The differentiated and undifferentiated MSCs were encountered to allogeneic splenocytes and the proliferation, CD44 activation marker, and cytokine release in the splenocytes were evaluated.
IPCs exhibited increased expression of MHC-I and CD80 that elicited an allogenic response including the activation-induced proliferation of splenocytes, activation of CD4 T cells, and IFNγ response.
MSCs acquire immunogenicity after differentiation to functional IPCs, which might cause decreased efficacy in the case of allogeneic transplantation. Careful precautions might be critical for saving the IPCs against the detrimental allogeneic responses.
尽管间充质干细胞（MSCs）被认为具有免疫逃避作用，甚至具有免疫抑制作用，但最近的证据表明，在某些源自 MSCs 的谱系中，同种异体免疫反应是不可避免的。鉴于同种异体 IPCs 和 MSCs 在临床前和临床研究中的重要性，本研究旨在探讨在同种异体移植的小鼠模型中，MSCs 向 IPCs 分化过程中免疫原性可能发生的变化。
选择 C57BL/6（H2D）和 BALB/c（H2D）两种小鼠品系，建立同种异体细胞移植模型。通过流式细胞术评估骨髓 MSCs 向 IPCs 分化过程中 H2D、CD80 和 Qa-2 分子的表达。将分化和未分化的 MSCs 与同种异体脾细胞相遇，评估脾细胞的增殖、CD44 激活标志物和细胞因子释放。
IPC 表达增加 MHC-I 和 CD80，引发同种异体反应，包括脾细胞的激活诱导增殖、CD4 T 细胞的激活和 IFNγ 反应。
MSCs 在向功能性 IPCs 分化后获得免疫原性，这可能导致同种异体移植的疗效降低。在同种异体反应中，为保护 IPCs，需要谨慎预防。
