Mesenchymal Stromal Cell-derived Exosomes Protect Against Abdominal Aortic Aneurysm Formation Through CD74 Modulation of Macrophage Polarization in Mice

Overview

Journal Stem Cell Res Ther

Publisher Biomed Central

Date 2024 Aug 4

PMID 39098899

Authors

Jiamin Xu

Jiling Zhao

Haiting Chen

Xi Tan

Wenfeng Zhang

Zhongnan Xia

Dejiang Yao

Yuhua Lei

Biao Xu

Zhonghai Wei

Jiaxin Hu

Affiliations

Soon will be listed here.

Abstract

Background: Mesenchymal stromal cell (MSC)-derived exosomes (MSC-Exo) have been recognized for their significant role in regulating macrophage polarization, a process crucial to the pathogenesis of abdominal aortic aneurysm (AAA). However, the therapeutic effects of MSC-Exo on AAA remain largely unexplored. Therefore, this study aimed to investigate the functional and mechanistic aspects of MSC-Exo in the progression of AAA.

Methods: The MSC-derived exosomes were characterized using Transmission Electron Microscopy, Nanoparticle Tracking Analysis, and Western blotting. An experimental mouse model of AAA was established through the administration of angiotensin II (Ang II) in male apoe mice and calcium chloride (CaCl) in male C57/B6 mice, with subsequent tail vein injection of exosomes to evaluate their efficacy against AAA. Macrophage polarization was assessed using immunofluorescence staining and WB analysis. Mechanistic analysis was performed using 4D Label-free Proteomics analysis.

Results: We found that intravenous administration of MSC-Exo induced M2 polarization of macrophages within an inflammatory environment, effectively impeding AAA development in Ang II or CaCl-induced AAA model. The therapeutic efficacy of MSC-Exo treatment was dependent on the presence of macrophages. Mechanistically, MSC-Exo suppressed the levels of cluster of differentiation 74 (CD74), modulating macrophage polarization through the TSC2-mTOR-AKT pathway. These findings highlight the potential of MSC-Exo as a therapeutic strategy for AAA by modulating macrophage polarization.

Citing Articles

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Chen T, Wan L, Xiao Y, Wang K, Wu P, Li C J Nanobiotechnology. 2024; 22(1):653.

PMID: 39443923 PMC: 11515499. DOI: 10.1186/s12951-024-02916-4.

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