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Mesenchymal Stromal Cell Therapy Alleviates Ovalbumin-Induced Chronic Airway Remodeling by Suppressing M2 Macrophage Polarization

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Abstract

Chronic asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Previous studies have shown that mesenchymal stromal/stem cells (MSCs) exert anti-inflammatory effects on asthma via regulation of the immune cells. However, the therapeutic mechanism of MSCs, especially the mechanism of airway remodeling in chronic asthma, remains to be elucidated. Here, we aimed to investigate the therapeutic effect of MSCs on airway remodeling in chronic asthma and explored the mechanisms by analyzing the polarization phenotype of macrophages in the lungs. We established a mouse model of chronic asthma induced by ovalbumin (OVA) and evaluated the effect of MSCs on airway remodeling. The data showed that MSCs treatment before the challenge exerted protective effects on OVA-induced chronic asthma, i.e., decreased the inflammatory cell infiltration, Th2 cytokine levels, subepithelial extracellular matrix deposition, and transforming growth factor β (TGF-β)/Smad signaling. Additionally, we found that MSCs treatment markedly suppressed macrophage M2 polarization in lung tissue. At the same time, MSCs treatment inhibited NF-κB p65 nuclear translocation, ER stress, and oxidative stress in the OVA-induced chronic allergic airway remodeling mice model. In conclusion, these results demonstrated that MSCs treatment prevents OVA-induced chronic airway remodeling by suppressing macrophage M2 polarization, which may be associated with the dual inhibition of ER stress and oxidative stress. This discovery may provide a new theoretical basis for the future clinical application of MSCs.

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Funding

This study was supported by the National Natural Science Foundation of China (No. 81770023).

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  1. Haiyang Yu and Guiyin Zhu contributed equally to this work.

Authors and Affiliations

  1. Department of Respiratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai, 200092, China

    Haiyang Yu, Guiyin Zhu, Qiangqiang Qin, Xueting Wang, Xuejun Guo & Wen Gu

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Contributions

Dr. Haiyang Yu and Guiyin Zhu contributed to the study conduct and drafted the manuscript. Qiangqiang Qin contributed to data analysis. Dr. Xueting Wang provided language help. Dr. Wen Gu and Dr. Xuejun Guo contributed to the study design and guide. All authors reviewed the manuscript.

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Correspondence to Xuejun Guo or Wen Gu.

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Yu, H., Zhu, G., Qin, Q. et al. Mesenchymal Stromal Cell Therapy Alleviates Ovalbumin-Induced Chronic Airway Remodeling by Suppressing M2 Macrophage Polarization. Inflammation (2024). https://doi.org/10.1007/s10753-024-01977-9

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