TY  - JOUR
AU  - Xiong, Zhizhong
AU  - Li, Xianzhe
AU  - Xie, Minghao
AU  - Guo, Jianping
AU  - Yin, Shi
AU  - Huang, Dayin
AU  - Jin, Longyang
AU  - Wang, Caiqin
AU  - Zhang, Fengxiang
AU  - Mao, Chaobin
AU  - Chen, Huaxian
AU  - Luo, Dandong
AU  - Tang, Haijie
AU  - Chen, Xijie
AU  - Lian, Lei
TI  - Small extracellular vesicles derived from adipose mesenchymal stem cells alleviate intestinal fibrosis by inhibiting the FAK/Akt signaling pathway via MFGE8.
JO  - Journal of gastroenterology
VL  - 59
IS  - 12
SN  - 0944-1174
CY  - Tokyo
PB  - Springer
M1  - DKFZ-2024-01901
SP  - 1092-1106
PY  - 2024
N1  - #EA:C070# / 2024 Dec;59(12):1092-1106
AB  - 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.
KW  - Intestinal fibrosis (Other)
KW  - Mesenchymal stem cells (Other)
KW  - Milk fat globule-EGF factor 8 (Other)
KW  - Small extracellular vesicles (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39305336
DO  - DOI:10.1007/s00535-024-02152-5
UR  - https://inrepo02.dkfz.de/record/293578
ER  -