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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2021, Vol. 41 Issue (7): 66-73    DOI: 10.13523/j.cb.2102034
综述     
间充质干细胞来源的外泌体治疗炎症性肠病研究进展*
李开秀,司维()
昆明理工大学灵长类转化医学研究院 昆明 650504
Progress in the Treatment of Inflammatory Bowel Diseases by Exosomes Derived from Mesenchymal Stem Cells
LI Kai-xiu,SI Wei()
Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650504, China
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摘要：

间充质干细胞主要通过免疫调控和旁分泌在炎症性疾病的治疗中发挥功能。MSC的旁分泌效应是通过分泌可溶性因子并释放外泌体而发挥作用。外泌体将DNA、蛋白质/肽、mRNA、microRNA、脂质和细胞器等成分转移到受体细胞中直接发挥功能。MSC-Exo替代MSC为炎症性肠病的治疗提供了一种新策略。总结不同组织(骨髓、脐带和脂肪)来源的MSC- Exo用于治疗炎症性肠病的研究进展。
关键词： 阿维链霉菌;  阿维菌素;  Tn5转座突变;  分子遗传工具;  间充质干细胞;  外泌体;  炎症性肠病    
Abstract:

Mesenchymal stem cells (MSC) play an important role in the treatment of inflammatory diseases through immune regulation and paracrine effect. The paracrine effect of MSC is mediated by secreting soble factors and releasing exosomes (Exo). Exosomes transfer DNA, proteins/peptides, mRNA, microRNA, lipids and organelles into recipient cells and display functions directly. Therefore, MSC-Exo instead of MSC provides a new strategy for the treatment of inflammatory bowel diseases. In this review, we summarize the progress of MSC-Exo derived from various tissues (bone marrow, umbilical cord and adipose) for the treatment of inflammatory bowel diseases.
Key words: Streptomyces avermitilis    Avermectin    Tn5 transposon mediated mutagenesis    Molecular genetic tool    Mesenchymal stem cells    Exosomes    Inflammatory bowel disease
收稿日期: 2021-02-25 出版日期: 2021-08-03
ZTFLH:  Q819  
基金资助: * 河北省科技计划农业关键共性技术攻关专项(18222916);河北省自然科学基金资助项目(C2019209399);* 国家自然科学基金资助项目(31872973)
通讯作者: 司维     E-mail: siw@lpbr.cn
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李开秀,司维. 间充质干细胞来源的外泌体治疗炎症性肠病研究进展*[J]. 中国生物工程杂志, 2021, 41(7): 66-73.

LI Kai-xiu,SI Wei. Progress in the Treatment of Inflammatory Bowel Diseases by Exosomes Derived from Mesenchymal Stem Cells. China Biotechnology, 2021, 41(7): 66-73.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2102034    或    https://manu60.magtech.com.cn/biotech/CN/Y2021/V41/I7/66

组织来源 靶向细胞 调控因子 信号通路 参考文献
BMSC - 抑制核转录因子:NF-κBp65
下调促炎因子:TNF-α、iNOS、COX-2、IL-1β
上调抗炎因子:IL-10
抑制氧化:MPO、MDA、SOD、GSH
抑制细胞凋亡:caspase-3、caspase-8、caspase-9		 NF-κBp65信号转导途径 [75]
BMSC M2β巨噬细胞 上调抗炎因子:IL-10、金属硫蛋白-2 - [76]
BMSC M2巨噬细胞 下调促炎因子:TNF-α、IL-6、IL-12、VEGF-A、IFN-γ、CCL-24、CCL-17
上调抗炎因子:IL-10、TGF-β		 JAK1/STAT1/STAT6信号通路 [77]
BMSC Treg细胞 下调促炎因子:IL-17、IL-6、TNF-α、IFN-γ
上调抗炎因子:IL-10		 - [78]
UCMSC 结肠巨噬细胞 下调促炎因子:TNF-α、IL-1β、IL-6、iNOS、IL-7
上调抗炎因子:IL-10		 IL-7受体的信号传导 [47]
UCMSC 外周血单核细胞 下调促炎因子:IFN-γ、TNF-α、IL-1β、TGF-β1
上调抗炎因子:IL-10		 - [82]
ADMSC - 下调炎症因子:MMP-9、TNF-α、NF-κB、IL-1β、IL-6、COX-2、ICAM-1、TLR-4
下调氧化应激指标:NOX-1,NOX-2、NOX-4、氧化蛋白
下调凋亡蛋白:Bax、caspase 3、PARP下调纤维化标记物:Smad3、TGF-β		 - [83]
表1  不同来源的MSC外泌体在炎症性肠病中的作用与机制
模型种属 组织来源 提取方法 注射剂量(μg) 注射频率 参考文献
Sprague Dawley 大鼠 BMSC 超速离心 50/100 /200 1次(造模后第1天注射,第4天取材) [75]
Sprague Dawley 大鼠 ADMSC 超速离心 50 3次(造模后第1天、第3天和第5天注射后取材) [83]
BALB/c小鼠 BMSC 超速离心 50 7次(造模后每天注射,注射7天后取材) [77]
KM小鼠 UCMSC 超速离心 400 3次(在造模期间第3天、第6天、第9天注射,造模11天后取材) [47]
C57BL/6小鼠 BMSC 超速离心 200 2次(造模后第1天和第9天) [76]
C57BL/6J小鼠 BMSC 超速离心 200 3次(造模后连续注射3天,第10天取材) [78]
C57BL/6小鼠 UCMSC 超速离心 200 1次(造模后第1天注射,第3天取材) [82]
表2  不同来源的MSC外泌体采取的提取方法、注射剂量及频率
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