%0 Journal Article
%A Xiong, Zhizhong
%A Li, Xianzhe
%A Xie, Minghao
%A Guo, Jianping
%A Yin, Shi
%A Huang, Dayin
%A Jin, Longyang
%A Wang, Caiqin
%A Zhang, Fengxiang
%A Mao, Chaobin
%A Chen, Huaxian
%A Luo, Dandong
%A Tang, Haijie
%A Chen, Xijie
%A Lian, Lei
%T Small extracellular vesicles derived from adipose mesenchymal stem cells alleviate intestinal fibrosis by inhibiting the FAK/Akt signaling pathway via MFGE8.
%J Journal of gastroenterology
%V 59
%N 12
%@ 0944-1174
%C Tokyo
%I Springer
%M DKFZ-2024-01901
%P 1092-1106
%D 2024
%Z #EA:C070# / 2024 Dec;59(12):1092-1106
%X Intestinal fibrosis is one of the most frequent and severe complications of Crohn's disease. Accumulating studies have reported that adipose mesenchymal stem cell-derived small extracellular vesicles (AMSC-sEVs) could alleviate renal fibrosis, hepatic fibrosis, etc., while their potential for treating intestinal fibrosis remains uncertain. Therefore, this study aims to determine the therapeutic effects of AMSC-sEVs on intestinal fibrosis and identify the mechanisms underlying these effects.AMSC-sEVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, and western blot. Whether AMSC-sEVs exert antifibrotic effects was investigated in two different murine models of intestinal fibrosis. Besides, AMSC-sEVs were co-cultured with primary human fibroblasts and CCD18co during transforming growth factor (TGF)-β1 stimulation. Label-free proteomics and rescue experiments were performed to identify candidate molecules in AMSC-sEVs. Transcriptome sequencing revealed changes in mRNA levels among different groups. Lastly, proteins related to relevant signaling pathways were identified by western blotting, and their expression and activation status were assessed.AMSC-sEVs positively expressed CD63 and Alix and presented a classical 'rim of a cup' and granule shape with approximately 43-100 nm diameter. AMSCs significantly alleviated intestinal fibrosis through secreted sEVs in vitro and in vivo. The milk fat globule-EGF factor 8 (MFGE8) was stably enriched in AMSC-sEVs and was an active compound contributing to the treatment of intestinal fibrosis by AMSCs. Mechanistically, AMSC-sEV-based therapies attenuated intestinal fibrosis by inhibiting the FAK/Akt signaling pathway.MFGE8-containing AMSC-sEVs attenuate intestinal fibrosis, partly through FAK/Akt pathway inhibition.
%K Intestinal fibrosis (Other)
%K Mesenchymal stem cells (Other)
%K Milk fat globule-EGF factor 8 (Other)
%K Small extracellular vesicles (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39305336
%R 10.1007/s00535-024-02152-5
%U https://inrepo02.dkfz.de/record/293578