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Therapeutic effects and potential targets of UC-MSC-Exo in a mouse model of COPD
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  • Published: 05 January 2026

Therapeutic effects and potential targets of UC-MSC-Exo in a mouse model of COPD

  • Yaping Zhou1 na1,
  • Li Li2 na1,
  • Jingran Xu2 na1,
  • Hui Gong3,
  • Zulipikaer Abudureheman3 &
  • …
  • Xiaoguang Zou2 

Scientific Reports , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cell biology
  • Diseases
  • Medical research
  • Stem cells

Abstract

This research investigated the therapeutic efficacy and potential targets of exosomes derived from umbilical cord mesenchymal stem cells (UC-MSC-Exo) in the context of chronic obstructive pulmonary disease (COPD). UC-MSC-Exo were isolated from the culture supernatant. A model of COPD was induced through exposure to cigarette smoke (CS) and airway lipopolysaccharide (LPS) instillation. Mice in the UC-MSC-Exo group received 100 µg of exosomes via tail vein injection. Lung function, computed tomography imaging of the lungs, bronchoalveolar lavage fluid cell count, plasma levels of inflammatory factors, as well as histological assessments using hematoxylin and eosin staining and Masson’s trichrome staining of lung tissue were employed to assess the therapeutic efficacy. Single-cell transcriptome sequencing was utilized to investigate the potential targets of UC-MSC-Exo in improving lung function and exerting anti-inflammatory effects in COPD mouse models. The UC-MSC-Exo group exhibited significant enhancements in pulmonary function parameters, attenuation of lung CT abnormalities, reduced BALF cell counts, and decreased levels of plasma inflammatory markers. Histological analysis confirmed decreased inflammatory infiltration and collagen deposition. Single-cell sequencing analysis suggested that UC-MSC-Exo might modulate CXCR4 expression, suppress inflammation, and facilitate lung regeneration by modulating macrophage functionality. This investigation introduces novel therapeutic avenues and potential targets for managing COPD.

Data availability

The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author(s).

References

  1. Christenson, S. A., Smith, B. M. & Bafadhel, M. Putcha, N. Chronic obstructive pulmonary disease. Lancet 399 (10342), 2227–2242 (2022).

    Google Scholar 

  2. Adeloye, D. et al. Global, regional, and National prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: A systematic review and modelling analysis. Lancet Resp. Med. 10 (5), 447–458 (2022).

    Google Scholar 

  3. Boers, E. et al. Global burden of chronic obstructive pulmonary disease through 2050. JAMA Netw. Open. 6 (12), e2346598 (2023).

    Google Scholar 

  4. Liao, J. et al. Burden of chronic obstructive pulmonary disease in china: A global burden of disease study on Temporal Trends, risk factor Contributions, and projected disease burden from 1990 to 2030. COPD-J Chronic Obstr. Pulm Dis. 22 (1), 2531016 (2025).

    Google Scholar 

  5. Riley, C. M. & Sciurba, F. C. Diagnosis and outpatient management of chronic obstructive pulmonary disease: A review. JAMA 321 (8), 786–797 (2019).

    Google Scholar 

  6. Jin, T., Liu, X., Li, G., Sun, S. & Xie, L. Intravenous injection of BMSCs modulate TsRNA expression and ameliorate lung remodeling in COPD mice. Stem Cell. Res. Ther. 15 (1), 450 (2024).

    Google Scholar 

  7. Ma, Y., Liu, X., Long, Y. & Chen, Y. Emerging therapeutic potential of mesenchymal stem Cell-Derived extracellular vesicles in chronic respiratory diseases: an overview of recent progress. Front. Bioeng. Biotechnol. 10, 845042 (2022).

    Google Scholar 

  8. Chang, Y., Wu, K. & Ding, D. Enhancing the therapeutic potential of human umbilical cord mesenchymal stem cells for osteoarthritis: The role of Platelet-Rich plasma and extracellular vesicles. Int. J. Mol. Sci. 26(8), 3785 (2025).

    Google Scholar 

  9. Wu, C. et al. Subchondral injection of human umbilical cord mesenchymal stem cells ameliorates knee osteoarthritis by inhibiting osteoblast apoptosis and TGF-beta activity. Stem Cell. Res. Ther. 16 (1), 235 (2025).

    Google Scholar 

  10. Li, H., Ji, X., Zhang, S. & Bi, R. Hypoxia and inflammatory factor preconditioning enhances the immunosuppressive properties of human umbilical cord mesenchymal stem cells. World J. Stem Cells. 15 (11), 999–1016 (2023).

    Google Scholar 

  11. Zhou, Y., Zhou, W., Li, Y. & Zhang, J. MSCs regulate oxidative stress through the Nrf2 pathway to treat chronic obstructive pulmonary disease. BMC Pulm Med. 25 (1), 304 (2025).

    Google Scholar 

  12. Chakraborty, A. et al. Induced pluripotent stem cell-derived mesenchymal stem cells reverse bleomycin-induced pulmonary fibrosis and related lung stiffness. Biomed. Pharmacother. 178, 117259 (2024).

    Google Scholar 

  13. Kim, Y. E. et al. SOCS3 protein mediates the therapeutic efficacy of mesenchymal stem cells against acute lung injury. Int. J. Mol. Sci. 24(9), 8256 (2023).

    Google Scholar 

  14. Song, Y. et al. The potential applications of artificially modified exosomes derived from mesenchymal stem cells in tumor therapy. Front. Oncol. 13, 1299384 (2023).

    Google Scholar 

  15. Kim, G. et al. Therapeutic potential of mesenchymal stem cells (MSCs) and MSC-Derived extracellular vesicles for the treatment of spinal cord injury. Int. J. Mol. Sci. 22(24), 13672 (2021).

    Google Scholar 

  16. Yari, H. et al. Emerging role of mesenchymal stromal cells (MSCs)-derived exosome in neurodegeneration-associated conditions: A groundbreaking cell-free approach. Stem Cell. Res. Ther. 13 (1), 423 (2022).

    Google Scholar 

  17. Lotfy, A., AboQuella, N. M. & Wang, H. Mesenchymal stromal/stem cell (MSC)-derived exosomes in clinical trials. Stem Cell. Res. Ther. 14 (1), 66 (2023).

    Google Scholar 

  18. Chen, Q., Lin, J., Deng, Z. & Qian, W. Exosomes derived from human umbilical cord mesenchymal stem cells protect against papain-induced emphysema by preventing apoptosis through activating VEGF-VEGFR2-mediated AKT and MEK/ERK pathways in rats. Regen Ther. 21, 216–224 (2022).

    Google Scholar 

  19. Guo-Parke, H., Linden, D., Weldon, S., Kidney, J. C. & Taggart, C. C. Deciphering Respiratory-Virus-Associated interferon signaling in COPD airway epithelium. Med. Lith. 58(1), 121 (2022).

    Google Scholar 

  20. Mathur, S. & Singh, P. Chronic obstructive pulmonary disease: lifestyle impact. Int. J. Prev. Med. 15, 67 (2024).

    Google Scholar 

  21. Song, J. H. & Kim, Y. Beyond the spirometry: new diagnostic modalities in chronic obstructive pulmonary disease. Tuberc Respir Dis. 88 (1), 1–13 (2025).

    Google Scholar 

  22. Tasch, J. et al. Clinical manifestations of subjects with the Non-Specific pulmonary function test pattern. Open. Respir Arch. 5 (3), 100253 (2023).

    Google Scholar 

  23. Celli, B. R. et al. Pharmacotherapy and lung function decline in patients with chronic obstructive pulmonary disease. A systematic review. Am. J. Respir Crit. Care Med. 203 (6), 689–698 (2021).

    Google Scholar 

  24. Gao, Y. et al. Mesenchymal stem cells-extracellular vesicles alleviate pulmonary fibrosis by regulating immunomodulators. World J. Stem Cells. 16 (6), 670–689 (2024).

    Google Scholar 

  25. Guo, H., Su, Y. & Deng, F. Effects of mesenchymal stromal Cell-Derived extracellular vesicles in lung diseases: current status and future perspectives. Stem Cell. Rev. Rep. 17(2), 440–458 (2021).

    Google Scholar 

  26. Lesage, F. & Thebaud, B. Mesenchymal stromal Cell-Derived extracellular vesicles for neonatal lung disease: Tiny particles, major promise, rigorous requirements for clinical translation. Cells 11(7), 1176 (2022).

  27. Du, Y. et al. Selenoprotein o as a regulator of macrophage metabolism in selenium deficiency-induced lung inflammation. Int. J. Biol. Macromol. 281 (Pt 1), 136232 (2024).

    Google Scholar 

  28. Mia, M. M. et al. YAP/TAZ are crucial regulators of macrophage-mediated pulmonary inflammation and fibrosis after bleomycin-induced injury. Eur. Respir. J. 65(6), 2301544 (2025).

    Google Scholar 

  29. Yin, H. et al. Acute silica exposure triggers pulmonary inflammation through macrophage pyroptosis: an experimental simulation. Front. Immunol. 13, 874459 (2022).

    Google Scholar 

  30. Luo, J., De Pascali, F., Richmond, G. W., Khojah, A. M. & Benovic, J. L. Characterization of a new WHIM syndrome mutant reveals mechanistic differences in regulation of the chemokine receptor CXCR4. J. Biol. Chem. 298 (2), 101551 (2022).

    Google Scholar 

  31. Bekaddour, N. et al. Targeting the chemokine receptor CXCR4 with Histamine analog to reduce inflammation in juvenile arthritis. Front. Immunol. 14, 1178172 (2023).

    Google Scholar 

  32. Shah, A. et al. Secretory trefoil factor 1 (TFF1) promotes gemcitabine resistance through chemokine receptor CXCR4 in pancreatic ductal adenocarcinoma. Cancer Lett. 598, 217097 (2024).

    Google Scholar 

  33. Wang, C. et al. Oxygen desaturation is associated with fibrocyte activation via epidermal growth factor Receptor/Hypoxia-Inducible factor-1alpha axis in chronic obstructive pulmonary disease. Front. Immunol. 13, 852713 (2022).

    Google Scholar 

  34. Zhang, X. et al. Astragaloside IV restores Th17/Treg balance via inhibiting CXCR4 to improve chronic obstructive pulmonary disease. Immunopharmacol. Immunotoxicol. 45 (6), 682–691 (2023).

    Google Scholar 

  35. Dupin, I. et al. CXCR4 blockade alleviates pulmonary and cardiac outcomes in early COPD. Am. J. Respir Cell. Mol. Biol. 73(4), 530–544 (2025).

    Google Scholar 

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Acknowledgements

Thank you very much to all the authors who participated in this paper.

Funding

This work was supported by the Kashi Regional Science and Technology Program Projects (No. KS2023012).

Author information

Author notes
  1. Yaping Zhou, Li Li and Jingran Xu contributed equally to this work.

Authors and Affiliations

  1. The 3rd Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Urumqi, 830000, China

    Yaping Zhou

  2. Department of Respiratory and Critical Care Medicine, First People′s Hospital of Kashi, Kashi, 844000, China

    Li Li, Jingran Xu & Xiaoguang Zou

  3. Clinical Research Center of Infectious Diseases (Pulmonary Tuberculosis), First People′s Hospital of Kashi, Kashi, 844000, China

    Hui Gong & Zulipikaer Abudureheman

Authors
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Contributions

X.Z. conceived and designed the study. Y.Z., L.L., J.X. performed the experiments. Y.Z., H.G, Z.A. conducted the analysis. Y.Z. wrote thearticle with the help of all other authors. All authors edited and proofread the article.

Corresponding author

Correspondence to Xiaoguang Zou.

Ethics declarations

Competing interests

The authors declare no competing interests.

Approval for animal experiments

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Animal Experiment Center of Xinjiang Medical University (IACUC−20231010−06 and 2023.10.10 of approval).

Consent to participate

Not applicable.

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Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1

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Cite this article

Zhou, Y., Li, L., Xu, J. et al. Therapeutic effects and potential targets of UC-MSC-Exo in a mouse model of COPD. Sci Rep (2026). https://doi.org/10.1038/s41598-025-34896-2

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  • Received: 20 August 2025

  • Accepted: 31 December 2025

  • Published: 05 January 2026

  • DOI: https://doi.org/10.1038/s41598-025-34896-2

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Keywords

  • Chronic obstructive pulmonary disease
  • Single-cell analysis
  • Umbilical cord mesenchymal stem cell exosomes
  • CXCR4
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