Human umbilical cord mesenchymal stem cell-derived exosomes prevent and alleviate experimental pulmonary fibrosis by modulating the cytoskeleton of macrophages.

BACKGROUND: Silicosis 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. Exosomes 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 pyroptosis, 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.