Extracellular vesicles derived from bone marrow mesenchymal stem cells attenuate dextran sodium sulfate-induced ulcerative colitis by promoting M2 macrophage polarization
Extracellular vesicles derived from bone marrow mesenchymal stem cells attenuate dextran sodium sulfate-induced ulcerative colitis by promoting M2 macrophage polarization
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DOI：
10.1016/j.intimp.2019.04.020
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发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
Yuan, Zhenglin
中科院分区：
文献类型：
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作者：
Cao, Li;Xu, Hanxin;Yuan, Zhenglin
骨髓间充质干细胞(BMSCs)分泌的细胞外小泡(EVS)在组织损伤中具有修复作用。然而，它们治疗慢性炎症性肠病溃疡性结肠炎(UC)的疗效和机制尚不清楚。为了探讨EVS在UC治疗中的作用及其可能机制，我们利用脂多糖(LPS)处理的巨噬细胞和葡聚糖硫酸钠(DSS)诱导的小鼠体内模型建立了UC的体外模型。在体外，EVS促进了内毒素诱导的巨噬细胞的增殖并抑制了炎症反应，表现为促炎因子(TNF-α、IL-6和IL-12)的上调和抗炎因子IL-10的下调。在体内模型中，EV通过减少体重减轻、疾病活动性指数、结肠粘膜损伤和严重程度以及增加结肠长度来改善UC的症状。此外，伴随着IL-10和转化生长因子-β水平的升高，以及血管内皮生长因子-A、干扰素-γ、IL-12、肿瘤坏死因子-α、CCL-24和CCL-17水平的下降。在机制上，EVS促进M2样巨噬细胞极化，其特征是M2标志物CD163的增加。此外，EVS对UC修复的正向作用可能与JAK1/STAT1/STAT6信号通路有关。总的来说，骨髓间充质干细胞来源的EVS对DSS诱导的UC具有积极的治疗作用，这可能是由于负面的炎症反应。
Extracellular vesicles (EVs) secreted by bone marrow mesenchymal stem cells (BMSCs) have shown repairing effects in tissue damage. However, their efficacy and mechanism in the treatment of ulcerative colitis (UC), a type of chronic inflammatory bowel disease, are unclear. To investigate the effects and possible mechanism of EVs in UC treatment, we established an in vitro model using lipopolysaccharide (LPS)-treated macrophages and an in vivo dextran sulfate sodium (DSS)-induced mouse model to mimic UC. In vitro, EVs promoted the proliferation and suppressed inflammatory response in LPS-induced macrophages, as demonstrated by the up-regulation of pro-inflammatory factors (TNF-alpha, IL-6, and IL-12) and down-regulation of the anti-inflammatory factor IL-10. In the in vivo model, EV administration ameliorated the symptoms of UC by reducing weight loss, disease activity index, and colon mucosa damage and severity while increasing colon length. This was additionally accompanied by the increase in IL-10 and TGF-beta levels and the decline in VEGF-A, IFN-gamma, IL-12, TNF-alpha, CCL-24, and CCL-17 levels. In terms of the mechanism, EVs promoted M2-like macrophage polarization, characterized by the increase in the M2 marker CD163. Furthermore, the positive effect of EVs on UC repair seemed to be related to the JAK1/STAT1/STAT6 signaling pathway. Collectively, BMSC-derived EVs exerted positive therapeutic effects against DSS-induced UC, which could be due to a negative inflammatory response.