Journal Article

DKFZ-2024-01901

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Small extracellular vesicles derived from adipose mesenchymal stem cells alleviate intestinal fibrosis by inhibiting the FAK/Akt signaling pathway via MFGE8.

Xiong, Z. ; Li, X. (First author)DKFZ* ; Xie, M. ; Guo, J. ; Yin, S. ; Huang, D. ; Jin, L. ; Wang, C. ; Zhang, F. ; Mao, C. ; Chen, H. ; Luo, D. ; Tang, H. ; Chen, X. ; Lian, L.

2024
Springer Tokyo

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Please use a persistent id in citations: doi:10.1007/s00535-024-02152-5

Abstract: 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.

Keyword(s): Intestinal fibrosis ; Mesenchymal stem cells ; Milk fat globule-EGF factor 8 ; Small extracellular vesicles

Note: #EA:C070# / 2024 Dec;59(12):1092-1106

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Contributing Institute(s):

1. C070 Klinische Epidemiologie und Alternf. (C070)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Springer ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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