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人脐带间充质干细胞来源的外泌体通过降低巨噬细胞中 NLRP3 炎性小体的活性缓解急性肝衰竭。

Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acute liver failure by reducing the activity of the NLRP3 inflammasome in macrophages.

机构信息

Office of Clinical Trial of Drug, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.

Guangzhou Saliai Stem Cell Science and Technology Company Limited, China.

出版信息

Biochem Biophys Res Commun. 2019 Jan 15;508(3):735-741. doi: 10.1016/j.bbrc.2018.11.189. Epub 2018 Dec 6.

DOI:10.1016/j.bbrc.2018.11.189
PMID:30528233
Abstract

Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXOs) play an important role in the regulation of the immune system and inflammatory responses; however, their role in acute liver failure (ALF) and related pathological conditions is unclear. In this study, we found that hUCMSC-EXOs can reduce the expression of the NLRP3 inflammasome and downstream inflammatory factors in acute liver failure. Western blot and ELISA results showed that hUCMSC-EXOs decreased the expression of NLRP3, caspase-1, IL-1β and IL-6 in LPS-stimulated RAW 264.7 macrophages. In vivo, the hUCMSC-EXOs repaired damaged liver tissue and decreased the expression of the NLRP3 inflammasome and the levels of ALT and AST in a mouse ALF model. The results of this study provide a new strategy for the application of human umbilical cord mesenchymal stem cell-derived exosomes in the treatment of ALF.

摘要

人脐带间充质干细胞来源的外泌体(hUCMSC-EXOs)在调节免疫系统和炎症反应中发挥重要作用;然而,它们在急性肝衰竭(ALF)及相关病理情况下的作用尚不清楚。在本研究中,我们发现 hUCMSC-EXOs 可降低急性肝衰竭中 NLRP3 炎性小体及下游炎症因子的表达。Western blot 和 ELISA 结果显示,hUCMSC-EXOs 降低了 LPS 刺激的 RAW264.7 巨噬细胞中 NLRP3、caspase-1、IL-1β 和 IL-6 的表达。在体内,hUCMSC-EXOs 修复了损伤的肝组织,降低了 NLRP3 炎性小体的表达以及小鼠 ALF 模型中 ALT 和 AST 的水平。本研究结果为将人脐带间充质干细胞来源的外泌体应用于急性肝衰竭的治疗提供了新策略。

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