Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Inflammatory Bowel Disease in Mice.

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Inflammatory Bowel Disease in Mice.
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源自人脐带间充质干细胞的外泌体可缓解小鼠炎症性肠病

DOI:
10.1155/2017/5356760
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发表时间:
2017
影响因子:
--
通讯作者:
Xu W
Xu W
中科院分区:
生物学3区
文献类型:
--
作者:
Mao F;Wu Y;Tang X;Kang J;Zhang B;Yan Y;Qian H;Zhang X;Xu W

文献摘要

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间充质干细胞(MSC)分泌的外泌体对多种组织损伤性疾病具有修复作用。本研究旨在探讨人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,hucMSCs)释放的exosomes对葡聚糖硫酸钠(dextran sulfate sodium,DSS-)诱导的炎症性肠病(inflammatory bowel disease,IBD)的治疗作用及其机制。我们发现吲哚菁绿色(ICG)标记的外泌体在注射后12小时归巢到IBD小鼠的结肠组织。外泌体作为hucMSC显著减轻小鼠中IBD的严重程度。IL-10基因表达增加,TNF-α、IL-1β、IL-6、iNOS和IL-7基因表达降低。此外,在IBD小鼠中,通过外泌体治疗减少巨噬细胞向结肠组织中的浸润。此外,我们提供的证据表明,在体外共培养与外来体抑制小鼠腹腔巨噬细胞中的iNOS和IL-7的表达。此外,我们发现IL-7在结肠炎患者的结肠组织中的表达高于健康对照组。我们的研究结果表明,来自hucMSC的外泌体对减轻DSS诱导的IBD具有深远的影响,并且可能通过调节巨噬细胞中的IL-7表达来发挥其影响。
Exosomes secreted by mesenchymal stem cells (MSCs) have shown repairing effects on several tissue injury diseases. In this study, we aimed to investigate the effects of exosomes released from human umbilical cord mesenchymal stem cells (hucMSCs) on the treatment of dextran sulfate sodium- (DSS-) induced inflammatory bowel disease (IBD) and to explore the underlying mechanism. We found that indocyanine green (ICG) labeled exosomes homed to colon tissues of IBD mice at 12 hours after injection. Exosomes significantly relieved the severity of IBD in mice as hucMSCs. The expression of IL-10 gene was increased while that of TNF-α, IL-1β, IL-6, iNOS, and IL-7 genes was decreased in the colon tissues and spleens of exosomes-treated mice. Furthermore, the infiltration of macrophages into the colon tissues was decreased by exosome treatment in IBD mice. In addition, we provided evidence that in vitro coculture with exosomes inhibited the expression of iNOS and IL-7 in mouse enterocoelia macrophages. Moreover, we found that the expression of IL-7 was higher in the colon tissues of colitis patients than that of healthy controls. Our findings suggest that exosomes from hucMSCs have profound effects on alleviating DSS-induced IBD and may exert their impact through the modulation of IL-7 expression in macrophages.