间充质干细胞衍生细胞外囊泡用于炎症性肠病的研究进展

doi:10.12092/j.issn.1009-2501.2026.02.012

摘要/Abstract

摘要：

炎症性肠病（inflammatory bowel disease，IBD）是一种以胃肠道慢性炎症为特征的复杂疾病，其临床治疗面临诸多挑战。尽管当前药物治疗方案在缓解临床症状方面展现出一定疗效，但长期应用仍存在感染等治疗相关风险，凸显出对新型治疗策略的迫切需求。近年来，间充质干细胞（mesenchymal stem cells，MSCs）衍生细胞外囊泡（extracellular vesicles，EVs）因其在免疫调节领域的独特优势，逐渐成为IBD治疗的研究新热点，有望成为IBD治疗领域的一种创新且有效的治疗策略。本文综述了EVs在IBD治疗领域中的最新进展，主要包括EVs的质量控制标准、免疫调节机制以及工程化策略等内容。本综述旨在为MSC-EVs在IBD的临床转化治疗领域提供参考。同时，探讨了通过工程化手段增强MSC-EVs药效的新策略，为该领域的研究开辟了创新思路。

关键词: 炎症性肠病, 间充质干细胞, 细胞外囊泡, 免疫调节, 工程化

Abstract:

Inflammatory bowel disease (IBD) is a complex disorder characterized by chronic inflammation in the gastrointestinal tract, posing numerous challenges in its clinical management. Although current pharmacological treatment regimens demonstrate certain efficacy in alleviating clinical symptoms, their long-term use is associated with treatment-related risks such as infections, highlighting the urgent need for novel therapeutic strategies. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have emerged as a novel research focus in the treatment of IBD due to their unique advantages in the field of immunoregulation, holding promise as an innovative and effective therapeutic strategy in this area. This article reviews the latest advancements in the use of EVs for IBD treatment, encompassing topics such as EV quality control standards, immunoregulatory mechanisms, and engineering strategies. The objective of this review is to provide guidance for the clinical translational application of MSC-EVs in IBD treatment. Additionally, it explores novel strategies to enhance the therapeutic efficacy of MSC-EVs through engineering approaches, opening up innovative avenues for research in this field.

Key words: inflammatory bowel disease, mesenchymal stem cells, extracellular vesicles, immune regulation, engineering

中图分类号:

R516.1

虞旭友, 张启祥, 刘嘉莉, 王广基, 周芳. 间充质干细胞衍生细胞外囊泡用于炎症性肠病的研究进展[J]. 中国临床药理学与治疗学, 2026, 31(2): 247-256.

Xuyou YU, Qixiang ZHANG, Jiali LIU, Guangji WANG, Fang ZHOU. Research progress on the application of extracellular vesicles derived from mesenchymal stem cells for inflammatory bowel disease[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(2): 247-256.

图/表 5

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作用机制	动物模型	给药剂量及频次	给药途径	参考文献
通过JAK1/STAT1/ STAT6通路促进M2巨噬细胞复极化	DSS小鼠	7天给药50 μg MSC-EVs	i.p.	[29]
通过miR-378a-5p/NLRP3轴调控巨噬细胞焦亡	DSS小鼠	3、6、9天给药1 mg MSC-EVs	i.v.	[38]
通过SPRY2/ERK轴促进M2巨噬细胞复极化	DSS小鼠	给药200 μg MSC-EVs	肠系膜注射（mesenteric injection）	[26]
保护肠道屏障的完整性，激活肠上皮细胞和肠道干细胞增殖	DSS小鼠	0、3、6天给药300 μg MSC-EVs	i.v.	[36]
激活Wnt信号通路，显著促进ISCs的增殖与分化，从而加速肠道上皮的再生	DSS及TNBS小鼠	4、6、8天给药300 μg MSC-EVs	i.p.	[37]
通过TSG-6修复小鼠黏膜屏障并维持肠道稳态	DSS及TNBS小鼠	第5天给药200 μg MSC-EVs	i.p.	[30]
促使M2b巨噬细胞极化，诱导产生IL-10抑制CD4⁺T细胞	DSS小鼠	2、4、6天给药100 μg MSC-EVs	i.p.	[39]
调整Th1/Th17的比例并促进诱导Treg细胞的表达	DSS小鼠	2、4天给药60 μg MSC-EVs	i.v.	[34]

作用机制	动物模型	给药剂量及频次	给药途径	参考文献
通过JAK1/STAT1/ STAT6通路促进M2巨噬细胞复极化	DSS小鼠	7天给药50 μg MSC-EVs	i.p.	[29]
通过miR-378a-5p/NLRP3轴调控巨噬细胞焦亡	DSS小鼠	3、6、9天给药1 mg MSC-EVs	i.v.	[38]
通过SPRY2/ERK轴促进M2巨噬细胞复极化	DSS小鼠	给药200 μg MSC-EVs	肠系膜注射（mesenteric injection）	[26]
保护肠道屏障的完整性，激活肠上皮细胞和肠道干细胞增殖	DSS小鼠	0、3、6天给药300 μg MSC-EVs	i.v.	[36]
激活Wnt信号通路，显著促进ISCs的增殖与分化，从而加速肠道上皮的再生	DSS及TNBS小鼠	4、6、8天给药300 μg MSC-EVs	i.p.	[37]
通过TSG-6修复小鼠黏膜屏障并维持肠道稳态	DSS及TNBS小鼠	第5天给药200 μg MSC-EVs	i.p.	[30]
促使M2b巨噬细胞极化，诱导产生IL-10抑制CD4⁺T细胞	DSS小鼠	2、4、6天给药100 μg MSC-EVs	i.p.	[39]
调整Th1/Th17的比例并促进诱导Treg细胞的表达	DSS小鼠	2、4天给药60 μg MSC-EVs	i.v.	[34]

策略	EVs来源	特点	药效作用	参考文献
免疫调节	小鼠骨髓MSCs来源EVs	高表达PD-L1的MSC-EVs	重塑免疫微环境	[43]
免疫调节	人牙周韧带MSCs来源EVs	热应激提升MSC-EVs产量	增强免疫调节作用	[47]
增加药效与递送效率	人脐带MSCs来源EVs	包封MSC-EVs的微胶囊系统	提升MSC-EVs的稳定性、靶向性及药效	[50]
	人胎盘MSCs来源EVs	结肠特异性递送	靶向结肠并可控释放MSC-EVs	[49]
	人胎盘MSCs来源EVs	MSC-EVs负载Ber	提高药物溶解度和生物利用度	[61]
	人骨髓MSCs来源EVs	MSC-EVs负载Wnt激动剂	增强药物积累和生物利用度	[62]
	人牙周韧带MSCs来源EVs	热应激提升MSC-EVs产量	提高MSC-EVs产量，增强药效	[47]
	小鼠脂肪MSCs来源EVs	缺氧提升MSC-EVs产量	同上	[48]
调控相关机制通路	人胎盘MSCs来源EVs	结肠特异性递送	抑制MAPK/NF-κB信号通路	[49]
调控相关机制通路	大鼠骨髓MSCs来源EVs	高表达miR-146a的MSC-EVs	调控NF-κB信号通路	[45]
减轻炎症反应	人脐带MSCs来源EVs	高表达IL-27的MSC-EVs	减少不良反应	[44]

策略	EVs来源	特点	药效作用	参考文献
免疫调节	小鼠骨髓MSCs来源EVs	高表达PD-L1的MSC-EVs	重塑免疫微环境	[43]
免疫调节	人牙周韧带MSCs来源EVs	热应激提升MSC-EVs产量	增强免疫调节作用	[47]
增加药效与递送效率	人脐带MSCs来源EVs	包封MSC-EVs的微胶囊系统	提升MSC-EVs的稳定性、靶向性及药效	[50]
	人胎盘MSCs来源EVs	结肠特异性递送	靶向结肠并可控释放MSC-EVs	[49]
	人胎盘MSCs来源EVs	MSC-EVs负载Ber	提高药物溶解度和生物利用度	[61]
	人骨髓MSCs来源EVs	MSC-EVs负载Wnt激动剂	增强药物积累和生物利用度	[62]
	人牙周韧带MSCs来源EVs	热应激提升MSC-EVs产量	提高MSC-EVs产量，增强药效	[47]
	小鼠脂肪MSCs来源EVs	缺氧提升MSC-EVs产量	同上	[48]
调控相关机制通路	人胎盘MSCs来源EVs	结肠特异性递送	抑制MAPK/NF-κB信号通路	[49]
调控相关机制通路	大鼠骨髓MSCs来源EVs	高表达miR-146a的MSC-EVs	调控NF-κB信号通路	[45]
减轻炎症反应	人脐带MSCs来源EVs	高表达IL-27的MSC-EVs	减少不良反应	[44]

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