derived from human umbilical cord mesenchymal stem cells significantly alleviate pulmonary inflammation and slow lung fibrosis in a mouse model.
hucMSC-Exos are associated with reduced pulmonary inflammation in silicotic mice.
Treatment with hucMSC-Exos slows the progression of lung fibrosis.
Inhibition of macrophage occurs following treatment with hucMSC-Exos.
Activation of the actin cytoskeleton signaling pathway is observed in treated silicotic mice.
hucMSC-Exos help maintain plasma membrane integrity in lung tissues affected by silicosis.
Simplified
BACKGROUND: is an occupational lung disease characterized by silicotic nodules and progressive pulmonary fibrosis, caused by long-term excessive inhalation of free silica. So far, no effective methods have been developed to delay or cure silicotic fibrosis. derived from human umbilical cord mesenchymal stem cells (hucMSC-Exos), which possess functions of intercellular communication, tissue repair and regeneration, offering a potential strategy for the treatment of silicosis.
METHODS AND RESULTS: In this study, exosomes were extracted from human umbilical cord mesenchymal stem cells (huc-MSCs) using differential centrifugation and characterized for subsequent experiments. A silica-induced silicosis mouse model was established. Lung CT scans were performed to assess pulmonary lesions, while blood oxygenation status was monitored. Histopathological analysis of lung tissues was conducted, and Western blot was used to evaluate inflammatory and fibrotic markers, aiming to investigate the therapeutic effects of hucMSCs and their exosomes on silicotic mice. High-throughput transcriptome sequencing of lung tissues was employed to screen differentially expressed genes and signaling pathways in the two treatment groups, followed by in vitro validation of the proposed mechanisms.
CONCLUSION: Our findings demonstrate that hucMSC-Exos alleviate pulmonary inflammation, slow lung fibrosis, inhibit macrophage , activate the actin cytoskeleton signaling pathway, and maintain plasma membrane integrity in silicotic mice. This study provides possible therapeutic targets and molecular mechanisms for silicosis, establishing a link among silicosis, cytoskeleton, and pyroptosis, while validating the protective effect of hucMSC-Exos on the lungs of silicotic mice.
Key numbers
5 of 5
Decrease in TNF-α Levels
Measured in serum of mice on days 28 and 56.
5 of 5
Reduction in Hydroxyproline Levels
Measured in lung tissues of mice across treatment groups.
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Declarations. Ethics approval and consent to participate: The animal research protocol was reviewed and approved by the Ethics Committee for Laboratory Animal Welfare of North China University of Science and Technology (SQ-20230060; Title: Prevention and treatment of neonatal umbilical cord mesenchymal stem cell derived exosomes on pulmonary fibrosis in mice; Date of approval: March 8, 2023). The manuscript adhered to the ARRIVE guidelines for the reporting of animal experiments. All animal experiments were carefully performed to avoid animal suffering. The original source of human umbilical cord mesenchymal stem cells (Han’s United Biotechnology Co., Ltd.) has confirmed that there was initial ethical approval for collection of human cells, and that the donors had signed informed consent. The original source of human cells (THP-1) (Ripart Biotechnology Co., Ltd., Hebei) has confirmed that there was initial ethical approval for collection of human cells, and that the donors had signed informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
