| Human placental mesenchymal stem cell-derived exosomes carrying hsa-let-7i-5p mitigate lung injury in a murine model of aspiration pneumonia |
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Ching-Wei Chuang1,2,3,4, Hong-Phuc Nguyen Vo5,6, Yen-Hua Huang7,8, I-Lin Tsai7, Chao-Yuan Chang1,4,9, Chun-Jen Huang1,2,3,4 |
1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
2Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
3Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
4Department of Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
5International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
6Department of Anesthesiology, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam
7Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
8Research Center of Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei, Taiwan
9Department of Medical Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan |
Corresponding author:
Chun-Jen Huang, Tel: +886 2 27361661 ext. 3229,
Email: cjhuang@tmu.edu.tw
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Received: 16 January 2025 • Revised: 12 June 2025 • Accepted: 17 June 2025 |
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| Abstract |
Background
Aspiration pneumonia (AP), which can be caused by gastric content inhalation into the lower airways, causes acute lung injury (ALI) through complex mechanisms, including inflammation, oxidative stress, and apoptosis. Here, we evaluated the efficacy of exosomes derived from human placental mesenchymal stem cells (hpMSCs) in mitigating ALI in a murine model of AP. We also investigated the role of hsa-let-7i-5p, the most abundant miRNA in hpMSC-derived exosomes, in this respect.
Methods
Adult male C57BL/6 mouse AP models were administered hpMSC-derived exosomes (APExo group) or phosphate-buffered saline (AP group) intra-tracheally. After 48 h, the mice were euthanized and evaluated. The effects of hsa-let-7i-5p were assessed by specific inhibition or overexpression.
Results
Compared with the APExo group, the AP group exhibited significantly greater ALI, as evidenced by histological damage, increased lung injury scores, impaired lung function, increased leukocyte infiltration, and elevated tissue edema (all P < 0.05). The untreated AP group also showed more inflammation, characterized by nuclear factor-κB upregulation, macrophage M1 polarization, and cytokine level elevation (tumor necrosis factor-α, interleukin-1β, and interleukin-6), as well as increased oxidation and activation of the apoptosis pathway (all P < 0.05). Notably, the therapeutic effects of hpMSC-derived exosomes were compromised by specific inhibition of hsa-let-7i-5p. Furthermore, engineered exosomes derived from genetically modified RAW264.7 overexpressing hsa-let-7i-5p demonstrated therapeutic effects against AP similar to those obtained with hpMSC-derived exosomes.
Conclusions
In a murine AP model, intra-tracheal administration of hpMSC-derived exosomes has ALI-mitigating effects, involving inflammation, oxidation, and apoptosis modulation, with hsa-let-7i-5p playing a pivotal mediating role. |
| Key Words:
Aspiration pneumonia; Exosomes; Hsa-let-7i microRNA; Lung injury; Mesenchymal stem cells; Mice |
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