Airway basal stem cell-derived extracellular vesicles modulate proliferation, migration and collagen deposition of fibroblasts

Lisi Luo; Huijie Yang; Junfeng Huang; Difei Chen; Yushan He; Jinsheng Lin; Haikang Zeng; Chu Hua; Zikai Lin; Minting Wu; Yuqin Ma; Qilin Deng; Ming Liu; Shiyue Li

doi:10.1186/s13287-025-04268-8

Stem Cell Research & Therapy (Mar 2025)

Airway basal stem cell-derived extracellular vesicles modulate proliferation, migration and collagen deposition of fibroblasts

Lisi Luo,
Huijie Yang,
Junfeng Huang,
Difei Chen,
Yushan He,
Jinsheng Lin,
Haikang Zeng,
Chu Hua,
Zikai Lin,
Minting Wu,
Yuqin Ma,
Qilin Deng,
Ming Liu,
Shiyue Li

Affiliations

Lisi Luo: Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University
Huijie Yang: Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University
Junfeng Huang: Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University
Difei Chen: Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University
Yushan He: Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University
Jinsheng Lin: Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University
Haikang Zeng: Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University
Chu Hua: Guangzhou Medical University
Zikai Lin: Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University
Minting Wu: Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University
Yuqin Ma: Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University
Qilin Deng: Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University
Ming Liu: Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University
Shiyue Li: Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University

DOI: https://doi.org/10.1186/s13287-025-04268-8
Journal volume & issue: Vol. 16, no. 1
pp. 1 – 14

Abstract

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Abstract Background Human bronchial epithelial cell-derived extracellular vesicles have demonstrated the ability to attenuate fibroblasts activation. However, the specific key effector cell populations mediating this inhibitory effect remain unidentified. Airway basal stem cells (BSCs), which serve as progenitor cells for bronchial epithelial cells, play a critical role in fibrotic remodeling processes and possess significant therapeutic potential. This study aimed to characterize BSC-derived extracellular vesicles (BSC-EVs) and investigate their regulatory influence on fibroblasts behavior. Methods Airway BSCs were collected through bronchoscopic brushing and differential centrifugation. Fibroblasts were subsequently treated with BSC-EVs at various concentrations to evaluate their dose- and time-dependent effects in vitro. The proteomic composition of BSC-EVs was analyzed using four-dimensional data-independent acquisition quantitative mass spectrometry (4D-DIA). Moreover, a bleomycin-induced pulmonary fibrosis model was established to evaluate the safety and preliminary efficacy of BSC-EVs. Results We successfully isolated and identified BSC-EVs, which expressed the nucleus-specific marker TP63, indicative of BSCs, but lacked the BSC marker KRT5. Our findings demonstrated that BSC-EVs enhanced fibroblasts proliferation and migration in a dose-dependent manner. Importantly, BSC-EVs significantly attenuated fibroblasts activation and promoted fibroblasts senescence. Utilizing 4D-DIA quantitative proteomics, we revealed that BSC-EVs modulate extracellular matrix remodeling processes and regulate the expression of key proteins, including collagen I/III and matrix metalloproteinases. Animal models utilizing intratracheal administration of BSC-EVs demonstrate efficient reduction of collagen deposition. Conclusion This study offers an extensive characterization of BSC-EVs, adhering to the guidelines set forth by MISEV2023. The findings underscore the significant therapeutic potential of BSC-EVs in the management of fibrotic diseases.

Published in Stem Cell Research & Therapy

ISSN: 1757-6512 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Medicine (General); Science: Chemistry: Organic chemistry: Biochemistry
Website: https://stemcellres.biomedcentral.com

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