间充质干细胞来源外泌体对免疫功能调控的作用与应用前景
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摘要
背景:间充质干细胞对自身免疫疾病展现出了良好的治疗作用,其分泌的外泌体携带了母细胞的生物活性物质,可调节机体免疫反应。因此,利用外泌体替代间充质干细胞治疗自身免疫疾病,逐渐成为目前研究的新热点。目的:总结间充质干细胞来源外泌体对免疫细胞的调控作用以及在自身免疫疾病中的应用前景。方法:以"mesenchymal stem cells,exosomes,extracellular vesicle,microvesicle,autoimmune,immunomodulatory"和"间充质干细胞,外泌体,自身免疫,免疫调节"为检索词,检索PubMed与CNKI数据库1990至2018年间相关文献,并纳入79篇文献进行综述。结果与结论:间充质干细胞来源外泌体对固有免疫、适应性免疫和抗原提呈均具有明显的抑制作用,在自身性免疫疾病,如多发性硬化、系统性红斑狼疮、移植物抗宿主病和1型糖尿病等治疗中取得了巨大的进展,并展现出了良好的应用前景。
BACKGROUND: Mesenchymal stem cells(MSCs) show significant therapeutic effects on autoimmune diseases. MSCs-derived exosomes(MSCs-Exo) contain biological active molecules from the MSCs, which can regulate immune responses in the body. Therefore, MSCs-Exo as an alternative of MSCs has been used in the treatment of autoimmune diseases, which has become a new focus of research. OBJECTIVE: To summarize the effects of MSCs-Exo on immune cells and its application in the treatment of autoimmune diseases.METHODS: The key words of "mesenchymal stem cells, exosomes, extracellular vesicle, microvesicle, autoimmune, immunomodulatory" in Chinese and English were used to retrieve related literature from 1990 to 2018 in PubMed and CNKI databases. Finally, 79 articles were used for review. RESULTS AND CONCLUSION: MSCs-Exo has immunosuppressive effects on innate immunity, adaptive immunity and antigen presentation. Moreover, MSCs-Exo has good application prospects and has achieved great progress in the treatment of autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus, graft versus host disease, and type 1 diabetes mellitus.
BACKGROUND: Mesenchymal stem cells(MSCs) show significant therapeutic effects on autoimmune diseases. MSCs-derived exosomes(MSCs-Exo) contain biological active molecules from the MSCs, which can regulate immune responses in the body. Therefore, MSCs-Exo as an alternative of MSCs has been used in the treatment of autoimmune diseases, which has become a new focus of research. OBJECTIVE: To summarize the effects of MSCs-Exo on immune cells and its application in the treatment of autoimmune diseases.METHODS: The key words of "mesenchymal stem cells, exosomes, extracellular vesicle, microvesicle, autoimmune, immunomodulatory" in Chinese and English were used to retrieve related literature from 1990 to 2018 in PubMed and CNKI databases. Finally, 79 articles were used for review. RESULTS AND CONCLUSION: MSCs-Exo has immunosuppressive effects on innate immunity, adaptive immunity and antigen presentation. Moreover, MSCs-Exo has good application prospects and has achieved great progress in the treatment of autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus, graft versus host disease, and type 1 diabetes mellitus.
引文
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[20]Bagher Z,Azami M,Ebrahimi-Barough S,et al.Differentiation of Wharton's Jelly-Derived Mesenchymal Stem Cells into Motor Neuron-Like Cells on Three-Dimensional Collagen-Grafted Nanofibers.Mol Neurobiol.2016;53(4):2397-2408.
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[22]Timmers L,Lim SK,Arslan F,et al.Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium.Stem Cell Res.2007;1(2):129-137.
[23]van Poll D,Parekkadan B,Cho CH,et al.Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo.Hepatology.2008;47(5):1634-1643.
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[26]Yu B,Zhang X,Li X.Exosomes derived from mesenchymal stem cells.Int J Mol Sci.2014;15(3):4142-4157.
[27]Pachler K,Ketterl N,Desgeorges A,et al.An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles.Int J Mol Sci.2017;18(7):E1413.
[28]Sun L,Li D,Song K,et al.Exosomes derived from human umbilical cord mesenchymal stem cells protect against cisplatin-induced ovarian granulosa cell stress and apoptosis in vitro.Sci Rep.2017;7(1):2552.
[29]Gong M,Yu B,Wang J,et al.Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells and promote angiogenesis.Oncotarget.2017;8(28):45200-45212.
[30]Nakamura Y,Miyaki S,Ishitobi H,et al.Mesenchymalstem-cell-derived exosomes accelerate skeletal muscle regeneration.FEBS Lett.2015;589(11):1257-1265.
[31]Kim HS,Choi DY,Yun SJ,et al.Proteomic analysis of microvesicles derived from human mesenchymal stem cells.JProteome Res.2012;11(2):839-849.
[32]Murray PJ,Allen JE,Biswas SK,et al.Macrophage activation and polarization:nomenclature and experimental guidelines.Immunity.2014;41(1):14-20.
[33]Li X,Liu L,Yang J,et al.Exosome Derived From Human Umbilical Cord Mesenchymal Stem Cell Mediates MiR-181c Attenuating Burn-induced Excessive Inflammation.EBioMedicine.2016;8:72-82.
[34]Domenis R,CifùA,Quaglia S,et al.Pro inflammatory stimuli enhance the immunosuppressive functions of adipose mesenchymal stem cells-derived exosomes.Sci Rep.2018;8(1):13325.
[35]Xu H,Barnes GT,Yang Q,et al.Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.J Clin Invest.2003;112(12):1821-1830.
[36]Lumeng CN,Bodzin JL,Saltiel AR.Obesity induces a phenotypic switch in adipose tissue macrophage polarization.J Clin Invest.2007;117(1):175-184.
[37]Zhao H,Shang Q,Pan Z,et al.Exosomes From AdiposeDerived Stem Cells Attenuate Adipose Inflammation and Obesity Through Polarizing M2 Macrophages and Beiging in White Adipose Tissue.Diabetes.2018;67(2):235-247.
[38]Phinney DG,Di Giuseppe M,Njah J,et al.Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs.Nat Commun.2015;6:8472.
[39]Marigo I,Dazzi F.The immunomodulatory properties of mesenchymal stem cells.Semin Immunopathol.2011;33(6):593-602.
[40]Biron CA,Nguyen KB,Pien GC,et al.Natural killer cells in antiviral defense:function and regulation by innate cytokines.Annu Rev Immunol.1999;17:189-220.
[41]Spaggiari GM,Capobianco A,Becchetti S,et al.Mesenchymal stem cell-natural killer cell interactions:evidence that activated NK cells are capable of killing MSCs,whereas MSCs can inhibit IL-2-induced NK-cell proliferation.Blood.2006;107(4):1484-1490.
[42]Fan Y,Herr F,Vernochet A,et al.Human Fetal Liver Mesenchymal Stem Cell-Derived Exosomes Impair Natural Killer Cell Function.Stem Cells Dev.2019;28(1):44-55.
[43]Whiteside TL.Immune modulation of T-cell and NK(natural killer)cell activities by TEXs(tumour-derived exosomes).Biochem Soc Trans.2013;41(1):245-251.
[44]Reiners KS,Dassler J,Coch C,et al.Role of Exosomes Released by Dendritic Cells and/or by Tumor Targets:Regulation of NK Cell Plasticity.Front Immunol.2014;5:91.
[45]Fitzner D,Schnaars M,van Rossum D,et al.Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis.J Cell Sci.2011;124(Pt 3):447-458.
[46]Blazquez R,Sanchez-Margallo FM,de la Rosa O,et al.Immunomodulatory Potential of Human Adipose Mesenchymal Stem Cells Derived Exosomes on in vitro Stimulated T Cells.Front Immunol.2014;5:556.
[47]Chen W,Huang Y,Han J,et al.Immunomodulatory effects of mesenchymal stromal cells-derived exosome.Immunol Res.2016;64(4):831-840.
[48]álvarez V,Sánchez-Margallo FM,Macías-García B,et al.The immunomodulatory activity of extracellular vesicles derived from endometrial mesenchymal stem cells on CD4+T cells is partially mediated by TGFbeta.J Tissue Eng Regen Med.2018;12(10):2088-2098.
[49]Zhang B,Yin Y,Lai RC,et al.Mesenchymal stem cells secrete immunologically active exosomes.Stem Cells Dev.2014;23(11):1233-1244.
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