Mesenchymal stem cells (MSCs) are emerging as a promising therapeutic option for inflammatory rheumatic and autoimmune diseases because they combine immunomodulatory, anti-inflammatory, and regenerative properties with a generally favorable safety profile.
Large recent meta-analyses of randomized controlled trials including more than 2,000 patients show that MSC transplantation can significantly reduce pain and improve joint function in osteoarthritis. Meaningful improvements have been reported in VAS and WOMAC scores after intra-articular injections from bone marrow, adipose tissue, or umbilical cord sources, without increasing adverse events compared with controls (Zeng et al., 2025; Zeng et al., 2024; Tian et al., 2024; Cao et al., 2025).
In systemic autoimmune diseases, MSCs have demonstrated the ability to:
These benefits were observed again with no clear signal of excess serious toxicity (Zeng et al., 2025; Mesa et al., 2023; Zeng et al., 2022; Zhou et al., 2020).
Specifically in RA, systematic reviews and meta-analyses describe MSC therapy as safe and well tolerated. Trends indicate reduced inflammation, better functional scores, and improved laboratory markers. However, benefits are often modest and may wane after 6–12 months without repeated treatment (Mesa et al., 2023; Zeng et al., 2022; Hwang et al., 2021; Karamini et al., 2020).
Across rheumatic conditions, current trials favor:
Important challenges remain:
Overall, current evidence supports MSCs as a relatively safe, experimentally effective adjunct for selected refractory inflammatory rheumatic diseases. They are best used within controlled clinical trials while standardized protocols, and long-term efficacy and safety, are more clearly established (Zeng et al., 2025; Hetta et al., 2025; Mesa et al., 2023; Zeng et al., 2024; Jasim et al., 2022; Zaripova et al., 2023; Feng et al., 2025; Munir & McGettrick, 2015; Sarsenova et al., 2021).
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