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Updated: Jun 17, 2026
Adoptive Transfer of IL-33-Stimulated Macrophages into Bleomycin-Induced Mouse Models to Study Their Effect on Idiopathic Pulmonary Fibrosis In Vivo
Published on: May 5, 2023
Human Urine Stem Cells Alleviate Pulmonary Fibrosis via Inhibiting Macrophage-Myofibroblast Transition
Zhou-Hang Zhang1,2, Guan-Lin Guo3, Xiao-Hui Guan1
1The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China.
Abstract:
Human Idiopathic Pulmonary Fibrosis (IPF) is a progressive and fatal lung disease with unknown etiology and lacking efficient treatments. Here, we reported that human urine stem cells (hUSCs) significantly alleviated pulmonary fibrosis via inhibiting macrophage-myofibroblast transition (MMT), which was identified as a pivotal pathological process in IPF, with the strong interaction among infiltrated macrophages, damaged alveolar epithelial cells, and myofibroblasts via single-nucleus RNA sequencing data analysis and co-immunostaining. In addition, hUSCs significantly alleviated pulmonary fibrosis by attenuating alveolar epithelial cell damage, reducing monocyte-derived macrophage infiltration, and suppressing MMT in the bleomycin-induced pulmonary fibrosis mouse model. Furthermore, we demonstrated hUSCs inhibited monocyte recruitment and MMT via paracrine actions in the macrophage-alveolar epithelial cell co-culture system. Mechanistically, DKK1, which was highly secreted by hUSCs and identified by Venn diagram analysis between the luminex assay in supernatants of THP1 treated with hUSC-CM and antibody array of hUSC-CM, might contribute to preventing MMT via suppressing the Wnt/β-catenin signaling pathway in macrophages. In summary, hUSCs exerted multifaceted protective effects against pulmonary fibrosis, at least in part through paracrine mechanisms involving DKK1 and its modulation of Wnt/β-catenin-associated fibrotic responses in MMT. Therefore, hUSCs might provide a potential therapeutic strategy for IPF clinically.
Insights
Human urine stem cells (hUSCs) show promise for treating idiopathic pulmonary fibrosis (IPF). These cells inhibit macrophage-myofibroblast transition (MMT), a key process in IPF, offering a potential new therapy.
Area of Science:
- Regenerative Medicine
- Pulmonary Medicine
- Cell Biology
Background:
- Idiopathic Pulmonary Fibrosis (IPF) is a severe, progressive lung disease with limited treatment options.
- Macrophage-myofibroblast transition (MMT) is a critical pathological process in IPF development.
- Understanding the cellular interactions and molecular mechanisms in IPF is crucial for therapeutic development.
Purpose of the Study:
- To investigate the therapeutic potential of human urine stem cells (hUSCs) in treating pulmonary fibrosis.
- To elucidate the mechanisms by which hUSCs alleviate fibrosis, focusing on MMT.
- To identify key molecular mediators involved in hUSC-mediated antifibrotic effects.
Main Methods:
- Single-nucleus RNA sequencing and co-immunostaining to analyze cellular interactions in IPF.
- Utilizing a bleomycin-induced pulmonary fibrosis mouse model to assess hUSC efficacy.
- Employing macrophage-alveolar epithelial cell co-culture systems to study paracrine mechanisms.
- Luminex assay and antibody array to identify secreted factors from hUSCs.
Main Results:
- hUSCs significantly alleviated pulmonary fibrosis in a mouse model.
- hUSCs inhibited MMT by reducing macrophage infiltration and attenuating epithelial cell damage.
- hUSCs exert therapeutic effects via paracrine signaling, with DKK1 identified as a key mediator suppressing Wnt/β-catenin signaling in macrophages.
Conclusions:
- hUSCs demonstrate significant therapeutic potential for idiopathic pulmonary fibrosis.
- The antifibrotic effects of hUSCs are mediated, in part, by DKK1 through the modulation of Wnt/β-catenin signaling.
- hUSCs represent a promising cell-based therapeutic strategy for IPF.
