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Updated: Jun 18, 2025
Isolation, Characterization, and Therapeutic Application of Extracellular Vesicles from Cultured Human Mesenchymal Stem Cells
Published on: September 23, 2022
Mesenchymal stromal cell-derived exosomes protect against abdominal aortic aneurysm formation through CD74 modulation
Jiamin Xu1, Jiling Zhao2, Haiting Chen3
1Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
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 (CaCl2) 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 CaCl2-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.
Insights
Mesenchymal stromal cell-derived exosomes (MSC-Exo) show therapeutic potential for abdominal aortic aneurysm (AAA). MSC-Exo promote M2 macrophage polarization, inhibiting AAA progression by modulating the CD74/TSC2-mTOR-AKT pathway.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Immunology
Background:
- Abdominal aortic aneurysm (AAA) pathogenesis involves macrophage polarization.
- Mesenchymal stromal cell-derived exosomes (MSC-Exo) regulate macrophage polarization.
- Therapeutic potential of MSC-Exo for AAA is largely unexplored.
Purpose of the Study:
- Investigate the functional and mechanistic aspects of MSC-Exo in AAA progression.
- Evaluate the therapeutic efficacy of MSC-Exo in AAA models.
- Elucidate the molecular mechanisms underlying MSC-Exo's effects on macrophage polarization in AAA.
Main Methods:
- Characterization of MSC-Exo (TEM, NTA, Western blotting).
- Establishment of mouse AAA models (Ang II or CaCl2 induced).
- Assessment of macrophage polarization (immunofluorescence, WB) and mechanistic analysis (4D Label-free Proteomics).
Main Results:
- Intravenous MSC-Exo administration induced M2 macrophage polarization.
- MSC-Exo effectively impeded AAA development in mouse models.
- MSC-Exo suppressed CD74 levels, modulating macrophage polarization via the TSC2-mTOR-AKT pathway.
Conclusions:
- MSC-Exo demonstrate therapeutic efficacy in AAA by promoting M2 macrophage polarization.
- The therapeutic effect of MSC-Exo is macrophage-dependent.
- MSC-Exo represent a promising therapeutic strategy for AAA targeting macrophage polarization.
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