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.
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The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author(s).
References
Christenson, S. A., Smith, B. M. & Bafadhel, M. Putcha, N. Chronic obstructive pulmonary disease. Lancet 399 (10342), 2227–2242 (2022).
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).
Boers, E. et al. Global burden of chronic obstructive pulmonary disease through 2050. JAMA Netw. Open. 6 (12), e2346598 (2023).
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).
Riley, C. M. & Sciurba, F. C. Diagnosis and outpatient management of chronic obstructive pulmonary disease: A review. JAMA 321 (8), 786–797 (2019).
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).
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).
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).
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).
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).
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).
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).
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).
Song, Y. et al. The potential applications of artificially modified exosomes derived from mesenchymal stem cells in tumor therapy. Front. Oncol. 13, 1299384 (2023).
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).
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).
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).
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).
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).
Mathur, S. & Singh, P. Chronic obstructive pulmonary disease: lifestyle impact. Int. J. Prev. Med. 15, 67 (2024).
Song, J. H. & Kim, Y. Beyond the spirometry: new diagnostic modalities in chronic obstructive pulmonary disease. Tuberc Respir Dis. 88 (1), 1–13 (2025).
Tasch, J. et al. Clinical manifestations of subjects with the Non-Specific pulmonary function test pattern. Open. Respir Arch. 5 (3), 100253 (2023).
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).
Gao, Y. et al. Mesenchymal stem cells-extracellular vesicles alleviate pulmonary fibrosis by regulating immunomodulators. World J. Stem Cells. 16 (6), 670–689 (2024).
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).
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).
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).
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).
Yin, H. et al. Acute silica exposure triggers pulmonary inflammation through macrophage pyroptosis: an experimental simulation. Front. Immunol. 13, 874459 (2022).
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).
Bekaddour, N. et al. Targeting the chemokine receptor CXCR4 with Histamine analog to reduce inflammation in juvenile arthritis. Front. Immunol. 14, 1178172 (2023).
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).
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).
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).
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).
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).
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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.
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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).
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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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DOI: https://doi.org/10.1038/s41598-025-34896-2