MSCs exert paracrine effects: anti inflammatory, anti apoptotic, anti oxidant, pro angiogenic, antimicrobial, and antifibrotic actions that improve epithelial/endothelial barrier function and fluid clearance in ARDS and other injuries (Harrell et al., 2019; Fernández-Francos et al., 2021; Qin & Zhao, 2020; Lopes-Pacheco et al., 2019; Behnke et al., 2020). They modulate innate and adaptive immune cells, shift macrophages to a reparative M2 phenotype, and can partly support alveolar epithelial regeneration or transdifferentiate into AT2 like cells in models (Harrell et al., 2019; Yuan et al., 2024; Zhang et al., 2025; Lopes-Pacheco et al., 2019).
| Indication | MSC role (evidence) | Key points | Citations |
|---|---|---|---|
| ARDS / COVID ARDS | Reduce cytokine storm, improve barrier integrity, enhance survival (animals; early trials, H7N9 study) | Safety shown; some signals of lower mortality, but larger RCTs needed | (Fernández-Francos et al., 2021; Qin & Zhao, 2020; Lopes-Pacheco et al., 2019; Chen et al., 2020) |
| COPD & asthma | Decrease inflammation, oxidative stress, remodeling; improve lung function (mostly preclinical; small trials) | Clinical trials show safety; limited efficacy so far | (Cruz & Rocco, 2020; Harrell et al., 2019; Abbaszadeh et al., 2022; Wang et al., 2021; Lai & Guo, 2024; Wecht & Rojas, 2016; Antoniou et al., 2018) |
| Idiopathic pulmonary fibrosis / chronic fibrotic ILD | Antifibrotic, pro-repair in models; phase I/II show safety | Optimal timing likely early disease; long-term effects unknown | (Cruz & Rocco, 2020; Yuan et al., 2024; Chen et al., 2021; Wecht & Rojas, 2016; Antoniou et al., 2018) |
| BPD, PAH, silicosis, pneumonia | Experimental and early clinical use, especially with UC MSCs | Benefit mainly in animal models | (Cruz & Rocco, 2020; Fernández-Francos et al., 2021; Zhang et al., 2025; Chen et al., 2021; Mohammadipoor et al., 2018) |
Figure: Key pulmonary indications explored for MSC therapy.
MSC extracellular vesicles (EVs)/exosomes reproduce many benefits of cells with lower immunogenicity and tumor risk and easier storage, and show efficacy in models of COPD, asthma, fibrosis and ARDS (Abbaszadeh et al., 2022; Zhang et al., 2025; Yiming et al., 2022; Mohammadipoor et al., 2018). Secretome based approaches are emerging as favored “cell free” therapeutics (Fernández-Francos et al., 2021; Yiming et al., 2022; Mohammadipoor et al., 2018).
Across >100 pulmonary clinical trials, IV MSCs (often bone marrow or umbilical cord derived) appear safe, but effects on lung function, symptoms and survival are modest and inconsistent so far (Cruz & Rocco, 2020; Wang et al., 2021; Chen et al., 2021; Antoniou et al., 2018). Critical gaps include best source (UC MSCs may be superior in ARDS), dose, route, timing, and need for repeated dosing or genetic/conditioning strategies to boost potency (Cruz & Rocco, 2020; Fernández-Francos et al., 2021; Wang et al., 2021; Regmi et al., 2024). In pulmonology, MSCs and their EVs are promising tools for inflammatory and fibrotic lung diseases, especially ARDS, COPD, asthma and IPF. For now they remain experimental: safe in early trials, clearly effective in animal models, but with human efficacy still to be proven in large, well designed studies.
Cruz, F., & Rocco, P. (2020). The potential of mesenchymal stem cell therapy for chronic lung disease. Expert Review of Respiratory Medicine, 14, 31 - 39. https://doi.org/10.1080/17476348.2020.1679628
Harrell, R., Sadikot, R., Pascual, J., Fellabaum, C., Jankovic, M., Jovicic, N., Djonov, V., Arsenijević, N., & Volarevic, V. (2019). Mesenchymal Stem Cell-Based Therapy of Inflammatory Lung Diseases: Current Understanding and Future Perspectives. Stem Cells International, 2019. https://doi.org/10.1155/2019/4236973
Fernández-Francos, S., Eiro, N., González-Galiano, N., & Vizoso, F. (2021). Mesenchymal Stem Cell-Based Therapy as an Alternative to the Treatment of Acute Respiratory Distress Syndrome: Current Evidence and Future Perspectives. International Journal of Molecular Sciences, 22. https://doi.org/10.3390/ijms22157850
Yuan, D., Bao, Y., & El-Hashash, A. (2024). Mesenchymal stromal cell-based therapy in lung diseases; from research to clinic. American journal of stem cells, 13 2, 37-58. https://doi.org/10.62347/jawm2040
Abbaszadeh, H., Ghorbani, F., Abbaspour-Aghdam, S., Kamrani, A., Valizadeh, H., Nadiri, M., Sadeghi, A., Shamsasenjan, K., Jadidi‐Niaragh, F., Roshangar, L., & Ahmadi, M. (2022). Chronic obstructive pulmonary disease and asthma: mesenchymal stem cells and their extracellular vesicles as potential therapeutic tools. Stem Cell Research & Therapy, 13. https://doi.org/10.1186/s13287-022-02938-5
Zhang, Z., Shan, X., Liang, C., Zhao, L., & Shan, X. (2025). Microvesicles derived from mesenchymal stem cells: A promising therapeutic strategy for acute respiratory distress syndrome-related pulmonary fibrosis?. World Journal of Stem Cells, 17. https://doi.org/10.4252/wjsc.v17.i1.101036
Qin, H., & Zhao, A. (2020). Mesenchymal stem cell therapy for acute respiratory distress syndrome: from basic to clinics. Protein & Cell, 11, 707 - 722. https://doi.org/10.1007/s13238-020-00738-2
Wang, M., Zhou, T., Zhang, Z., Liu, H., Zheng, Z., & Xie, H. (2021). Current therapeutic strategies for respiratory diseases using mesenchymal stem cells. MedComm, 2, 351 - 380. https://doi.org/10.1002/mco2.74
Chen, X., Wang, F., Huang, Z., Wu, Y., Geng, J., & Wang, Y. (2021). Clinical applications of mesenchymal stromal cell-based therapies for pulmonary diseases: An Update and Concise Review. International Journal of Medical Sciences, 18, 2849 - 2870. https://doi.org/10.7150/ijms.59218
Lai, S., & Guo, Z. (2024). Stem cell therapies for chronic obstructive pulmonary disease: mesenchymal stem cells as a promising treatment option. Stem Cell Research & Therapy, 15. https://doi.org/10.1186/s13287-024-03940-9
Lopes-Pacheco, M., Robba, C., Rocco, P., & Pelosi, P. (2019). Current understanding of the therapeutic benefits of mesenchymal stem cells in acute respiratory distress syndrome. Cell Biology and Toxicology, 36, 83 - 102. https://doi.org/10.1007/s10565-019-09493-5
Behnke, J., Kremer, S., Shahzad, T., Chao, C., Böttcher-Friebertshäuser, E., Morty, R., Bellusci, S., & Ehrhardt, H. (2020). MSC Based Therapies—New Perspectives for the Injured Lung. Journal of Clinical Medicine, 9. https://doi.org/10.3390/jcm9030682
Regmi, S., Ganguly, A., Pathak, S., Primavera, R., Chetty, S., Wang, J., Patel, S., & Thakor, A. (2024). Evaluating the therapeutic potential of different sources of mesenchymal stem cells in acute respiratory distress syndrome. Stem Cell Research & Therapy, 15. https://doi.org/10.1186/s13287-024-03977-w
Wecht, S., & Rojas, M. (2016). Mesenchymal stem cells in the treatment of chronic lung disease. Respirology, 21, 1366 - 1375. https://doi.org/10.1111/resp.12911
Antoniou, K., Karagiannis, K., Tsitoura, E., Bibaki, E., Lasithiotaki, I., Proklou, A., Spandidos, D., & Tzanakis, N. (2018). Clinical applications of mesenchymal stem cells in chronic lung diseases. Biomedical Reports, 8, 314 - 318. https://doi.org/10.3892/br.2018.1067
Y., Liu, X., Long, Y., & Chen, Y. (2022). Emerging Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Chronic Respiratory Diseases: An Overview of Recent Progress. Frontiers in Bioengineering and Biotechnology, 10. https://doi.org/10.3389/fbioe.2022.845042
Mohammadipoor, A., Antebi, B., Batchinsky, A., & Cancio, L. (2018). Therapeutic potential of products derived from mesenchymal stem/stromal cells in pulmonary disease. Respiratory Research, 19. https://doi.org/10.1186/s12931-018-0921-x
Chen, J., Hu, C., Chen, L., Tang, L., Zhu, Y., Xu, X., Chen, L., Gao, H., Lu, X., Yu, L., Dai, X., Xiang, C., & Li, L. (2020). Clinical Study of Mesenchymal Stem Cell Treatment for Acute Respiratory Distress Syndrome Induced by Epidemic Influenza A (H7N9) Infection: A Hint for COVID-19 Treatment. Engineering (Beijing, China), 6, 1153 - 1161. https://doi.org/10.1016/j.eng.2020.02.006