间充质干细胞外泌体的免疫调节功能及其在自身免疫炎性疾病中的应用

doi:10.3877/cma.j.issn.2095-1221.2020.04.009

间充质干细胞（MSCs）来源的外泌体携带了母细胞的生物活性物质，具有和MSCs相似的生物学功能。最新的研究表明，MSCs来源的外泌体能通过影响非特异性免疫和获得性免疫中的多种免疫细胞发挥免疫调控作用，并在多种自身免疫炎性疾病中展现出良好的应用前景。本文就其免疫调节功能及其在自身免疫炎性疾病应用中的研究进展做一综述，旨在为研究自身免疫炎性疾病的治疗提供新的思路。

关键词: 间充质干细胞, 外泌体, 免疫调节

Exosomes derived from mesenchymal stem cells (MSCs) carry bioactive substances of parental cells, which have similar biological functions to MSCs. The recent studies show that MSC-derived exosomes play an important role in immune regulation by influencing immune cells in nonspecific and acquired immunity, and have a promising future in treatment of different autoimmune inflammatory diseases. In this paper, the immunomodulatory properties of MSCs-derived exosomes and their application in autoimmune diseases are reviewed, providing novel insights for the treatment of autoimmune inflammatory diseases.

Key words: Mesenchymal stem cells, Exosome, Immunoregulation

图1 外泌体的形成过程

表1 MSCs来源的外泌体在自身免疫炎性疾病中的研究进展

外泌体来源	疾病（模型）	应用方式	外泌体用量	作用机理	参考文献
人胚胎干诱导来源的MSCs	颞下颌关节炎（SD大鼠）	局部注射	100 μg	AKT，ERK，AMPK信号通路激活	[34]
鼠脂肪来源MSCs	肥胖患者脂肪慢性炎症（C57BL/6小鼠）	腹腔注射	30 μg	诱导巨噬细胞向M2转化	[19]
人骨髓来源MSCs	慢性移植物抗宿主疾病（Balb/c小鼠）	尾静脉注射	100 μg	诱导调节性T细胞产生抑制辅助性T细胞17，减少CD4⁺ T细胞渗透	[35]
人骨髓来源MSCs	1型糖尿病，葡萄膜视网膜炎（C57BL/6J小鼠）	尾静脉注射	30 μg	抑制抗原提呈细胞、辅助T细胞17激活	[36]
人骨髓来源MSCs	哮踹患者外周血单核细胞	培养基	-	上调TGF-β1和IL-10，促进调节性T细胞增殖和免疫抑制功能	[37]
人胚胎干诱导来源的MSCs	同种异体皮肤移植（C57BL/6J和BALB/cJ小鼠）	皮下注射	0.3 μg	增加调节性T细胞数量	[38]
人脐带来源MSCs	烧伤导致的过度炎症反应（SD大鼠）	尾静脉注射	800 μg	miRNA-181c抑制TLR4信号通路	[17]

表1 MSCs来源的外泌体在自身免疫炎性疾病中的研究进展

外泌体来源	疾病（模型）	应用方式	外泌体用量	作用机理	参考文献
人胚胎干诱导来源的MSCs	颞下颌关节炎（SD大鼠）	局部注射	100 μg	AKT，ERK，AMPK信号通路激活	[34]
鼠脂肪来源MSCs	肥胖患者脂肪慢性炎症（C57BL/6小鼠）	腹腔注射	30 μg	诱导巨噬细胞向M2转化	[19]
人骨髓来源MSCs	慢性移植物抗宿主疾病（Balb/c小鼠）	尾静脉注射	100 μg	诱导调节性T细胞产生抑制辅助性T细胞17，减少CD4⁺ T细胞渗透	[35]
人骨髓来源MSCs	1型糖尿病，葡萄膜视网膜炎（C57BL/6J小鼠）	尾静脉注射	30 μg	抑制抗原提呈细胞、辅助T细胞17激活	[36]
人骨髓来源MSCs	哮踹患者外周血单核细胞	培养基	-	上调TGF-β1和IL-10，促进调节性T细胞增殖和免疫抑制功能	[37]
人胚胎干诱导来源的MSCs	同种异体皮肤移植（C57BL/6J和BALB/cJ小鼠）	皮下注射	0.3 μg	增加调节性T细胞数量	[38]
人脐带来源MSCs	烧伤导致的过度炎症反应（SD大鼠）	尾静脉注射	800 μg	miRNA-181c抑制TLR4信号通路	[17]

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Immunomodulatory properties of mesenchymal stem cell-derived exosomes and its application in autoimmune inflammatory diseases treatment

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Immunomodulatory properties of mesenchymal stem cell-derived exosomes and its application in autoimmune inflammatory diseases treatment