The effects of mesenchymal stem cells on asthma

Abstract

Asthma is an inflammatory disease of the respiratory system characterized by cough, shortness of breath, wheezing, sputum, obstruction and bronchial hyperactivity. Asthma leads to disruption of epithelial structure, subepithelial fibrosis, inflammation, and ultimately airway reorganization. MSCs migrate into inflammatory tissue and settle there. Once in the tissue, the MSCs suppress inflammation and improve the internal structure of the tissue. These effects are achieved by transforming into tissue cells, producing anti-inflammatory and growth factors, and releasing microRNAs and extracellular vesicles. The effect of MSCs on asthma is based mostly on in vivo experimental animal models and in vitro studies of airway cells. While ovalbumin, cockroach extract and house dust mite are mostly used for in vivo experimental animal models, airway smooth muscle cells are mostly used for in vivo studies. This study aims to objectively present the information obtained from reliable articles about whether MSCs can be used in the treatment of asthma, a chronic inflammatory lung disease.

Keywords

• Asthma models
• identification of MSCs
• inflammatory disease
• mesenchymal stem cells

References

1. Ahmadi, M., Rahbarghazi, R., Aslani, M. R., Shahbazfar, A. A., Kazemi, M., & Keyhanmanesh, R. (2017). Bone marrow mesenchymal stem cells and their conditioned media could potentially ameliorate ovalbumin-induced asthmatic changes. Biomedicine & Pharmacotherapy, 85, 28-40. doi:10.1016/j.biopha.2016.11.127
2. Ahmadi, M., Rahbarghazi, R., Shahbazfar, A. A., Baghban, H., & Keyhanmanesh, R. (2018). Bone marrow mesenchymal stem cells modified pathological changes and immunological responses in ovalbumin-induced asthmatic rats possibly by the modulation of miRNA155 and miRNA133. General Physiology and Biophysics, 37(3), 263-74.doi:10.4149/gpb_2017052
3. Banno, A., Reddy, Aravind T., Lakshmi, Sowmya P., & Reddy, Raju C. (2020). Bidirectional interaction of airway epithelial remodeling and inflammation in asthma. Clinical Science, 134(9), 1063-1079. doi:10.1042/cs20191309
4. Bao, X. H., Gao, F., Athari, S. S., & Wang, H. (2023). Immunomodulatory effect of IL‐35 gene‐transfected mesenchymal stem cells on allergic asthma. Fundamental & Clinical Pharmacology, 37(1), 116-124.doi:10.1111/fcp.12823
5. Bonfield, T. L., Koloze, M., Lennon, D. P., Zuchowski, B., Yang, S. E., & Caplan, A. I. (2010). Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model. American Journal of Physiology-Lung Cellular and Molecular Physiology, 299(6), L760-L770.doi:10.1152/ajplung.00182.2009
6. Brychtova, M., Thiele, J.-A., Lysak, D., Holubova, M., Kralickova, M., & Vistejnova, L. (2019). Mesenchymal stem cells as the near future of cardiology medicine--truth or wish? Biomedical Papers of the Medical Faculty of Palacky University in Olomouc, 163(1).
7. Castro, L. L., Kitoko, J. Z., Xisto, D. G., Olsen, P. C., Guedes, H. L., Morales, M. M., ... & Rocco, P. R. (2020). Multiple doses of adipose tissue-derived mesenchymal stromal cells induce immunosuppression in experimental asthma. Stem Cells Translational Medicine, 9(2), 250-260. doi:10.1002/sctm.19-0120
8. Cevhertas, L., Ogulur, I., Maurer, D. J., Burla, D., Ding, M., Jansen, K., . . . Akdis, C. A. (2020). Advances and recent developments in asthma in 2020. Allergy, 75(12), 3124-3146.

9. Choi, J. Y., Hur, J., Jeon, S., Jung, C. K., & Rhee, C. K. (2022). Effects of human adipose tissue-and bone marrow-derived mesenchymal stem cells on airway inflammation and remodeling in a murine model of chronic asthma. Scientific Reports, 12(1), 12032.doi:10.1038/s41598-022-16165-8
10. Cui, Z., Feng, Y., Li, D., Li, T., Gao, P., & Xu, T. (2020). Activation of aryl hydrocarbon receptor (AhR) in mesenchymal stem cells modulates macrophage polarization in asthma. Journal of Immunotoxicology, 17(1), 21-30. doi:10.1080/1547691X.2019.1706671
11. Di Cicco, M., Ghezzi, M., Kantar, A., Song, W.-J., Bush, A., Peroni, D., & D'Auria, E. (2023). Pediatric obesity and severe asthma: Targeting pathways driving inflammation. Pharmacological Research, 188, 106658.
12. Dong, L., Wang, Y., Zheng, T., Pu, Y., Ma, Y., Qi, X., . . . Mao, C. (2021). Hypoxic hUCMSC-derived extracellular vesicles attenuate allergic airway inflammation and airway remodeling in chronic asthma mice. Stem Cell Research & Therapy, 12(1).
13. Dong, L., Wang, Y., Zheng, T., Pu, Y., Ma, Y., Qi, X., ... & Mao, C. (2021). Hypoxic hUCMSC-derived extracellular vesicles attenuate allergic airway inflammation and airway remodeling in chronic asthma mice. Stem Cell Research & Therapy, 12, 1-14.
14. Du, Y. M., Zhuansun, Y. X., Chen, R., Lin, L., Lin, Y., & Li, J. G. (2018). Mesenchymal stem cell exosomes promote immunosuppression of regulatory T cells in asthma. Experimental Cell Research, 363(1), 114-120. doi:10.1016/j.yexcr.2017.12.021
15. Dunbar, H., Hawthorne, I. J., Tunstead, C., Dunlop, M., Volkova, E., Weiss, D. J., ... & English, K. (2025). The VEGF‐Mediated Cytoprotective Ability of MIF‐Licensed Mesenchymal Stromal Cells in House Dust Mite‐Induced Epithelial Damage. European Journal of Immunology, 55(1), e202451205. doi:10.1002/eji.202451205
16. Fang, Q., Wu, W., Xiao, Z., Zeng, D., Liang, R., Wang, J., ... & Zheng, S. G. (2024). Gingival-derived mesenchymal stem cells alleviate allergic asthma inflammation via HGF in animal models. Iscience, 27(5). doi:10.1016/j.isci.2024.109818.
17. Feng, C. Y., Bai, S. Y., Li, M. L., Zhao, J. Y., Sun, J. M., Bao, H. J., . . . Su, X. M. (2022). Adipose-Derived Mesenchymal Stem Cell-Derived Exosomal miR-301a-3p Regulates Airway Smooth Muscle Cells During Asthma by Targeting STAT3. Journal of Asthma and Allergy, 15, 99-110. doi:10.2147/JAA.S335680
18. Firouzabadi, S. R., Mohammadi, I., Ghafourian, K., Kiani, A., & Hashemi, S. M. (2024). Mesenchymal Stem Cell-Derived Extracellular Vesicle Therapy for Asthma in Murine Models: A Systematic Review and Meta-analysis. Stem Cell Reviews and Reports, 20(5), 1162-1183. doi:10.1007/s12015-024-10704-8
19. Ge, X., Bai, C., Yang, J., Lou, G., Li, Q., & Chen, R. (2013). Effect of mesenchymal stem cells on inhibiting airway remodeling and airway inflammation in chronic asthma. Journal of Cellular Biochemistry, 114(7), 1595-1605. doi:10.1002/jcb.24501
20. Ghalavand, M., Gouvarchin Ghaleh, H. E., Khafaei, M., Paryan, M., Kondori, B. J., Nodoushan, M. M., ... & Mohammadi-Yeganeh, S. (2023). Effect of calcitriol treated mesenchymal stem cells as an immunomodulation micro-environment on allergic asthma in a mouse model. Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders), 23(8), 1096-1103.doi:10.2174/1871530323666230127115847
21. Gu, W., Zheng, T., Li, W., Luo, X., Xu, X., Wang, Y., ... & Dong, L. (2025). Migrasomes derived from human umbilical cord mesenchymal stem cells: a new therapeutic agent for ovalbumin-induced asthma in mice. Stem Cell Research & Therapy, 16(1), 26.doi:10.1186/s13287-025-04145-4
22. He, X. Y., Han, M. M., Zhao, Y. C., Tang, L., Wang, Y., Xing, L., ... & Jiang, H. L. (2024). Surface-engineered mesenchymal stem cell for refractory asthma therapy: Reversing airway remodeling. Journal of Controlled Release, 376, 972-984.doi:10.1016/j.jconrel.2024.10.056
23. Hur, J., Kang, J. Y., Kim, Y. K., Lee, S. Y., Jeon, S., Kim, Y., ... & Rhee, C. K. (2020). Evaluation of human MSCs treatment frequency on airway inflammation in a mouse model of acute asthma. Journal of Korean Medical Science, 35(23). doi:10.3346/jkms.2020.35.e188
24. Kang, S. Y., Park, D. E., Song, W. J., Bae, B. R., Lee, J. W., Sohn, K. H., ... & Cho, S. H. (2017). Immunologic regulatory effects of human umbilical cord blood‐derived mesenchymal stem cells in a murine ovalbumin asthma model. Clinical & Experimental Allergy, 47(7), 937-945.doi:10.1111/cea.12920
25. Kapoor, S., Patel, S. A., Kartan, S., Axelrod, D., Capitle, E., & Rameshwar, P. (2012). Tolerance-like mediated suppression by mesenchymal stem cells in patients with dust mite allergy–induced asthma. Journal of Allergy and Clinical Immunology, 129(4), 1094-1101. doi:10.1016/j.jaci.2011.10.048
26. Ke, X., Do, D. C., Li, C., Zhao, Y., Kollarik, M., Fu, Q., ... & Gao, P. (2019). Ras homolog family member A/Rho-associated protein kinase 1 signaling modulates lineage commitment of mesenchymal stem cells in asthmatic patients through lymphoid enhancer–binding factor 1. Journal of Allergy and Clinical Immunology, 143(4), 1560-1574. doi:10.1016/j.jaci.2018.08.023
27. Keyhanmanesh, R., Rahbarghazi, R., Aslani, M. R., Hassanpour, M., & Ahmadi, M. (2018). Systemic delivery of mesenchymal stem cells condition media in repeated doses acts as magic bullets in restoring IFN-γ/IL-4 balance in asthmatic rats. Life Sciences, 212, 30-36. doi:10.1016/j.lfs.2018.09.049
28. Lambrecht, B. N., Persson, E. K., & Hammad, H. (2017). Myeloid Cells in Asthma Myeloid Cells in Health and Disease (pp. 739-757).
29. Leite-Santos, F., Tamashiro, E., Murashima, A. D. A. B., Anselmo-Lima, W. T., & Valera, F. C. (2023). Which are the best murine models to study Eosinophilic Chronic Rhinosinusitis? A contemporary review. Brazilian Journal of Otorhinolaryngology, 89(6), 101328.doi:10.1016/j.bjorl.2023.101328
30. Luo, X., Wang, Y., Mao, Y., Xu, X., Gu, W., Li, W., ... & Dong, L. (2024). Nebulization of Hypoxic hUCMSC-EVs Attenuates Airway Epithelial Barrier Defects in Chronic Asthma Mice by Transferring CAV-1. International Journal of Nanomedicine, 10941-10959.doi:10.2147/ijn.s476151
31. Marchi, S., Guilbaud, E., Tait, S. W., Yamazaki, T., & Galluzzi, L. (2023). Mitochondrial control of inflammation. Nature Reviews Immunology, 23(3), 159-173. doi:10.1038/s41577-022-00760-x.
32. Marinas-Pardo, L., Mirones, I., Amor-Carro, O., Fraga-Iriso, R., Lema-Costa, B., Cubillo, I., . . . Ramos-Barbon, D. (2014). Mesenchymal stem cells regulate airway contractile tissue remodeling in murine experimental asthma. Allergy, 69(6), 730-740. doi:10.1111/all.12392
33. Milián, E., & Díaz, A. M. (2004). Allergy to house dust mites and asthma. Puerto Rico Health Sciences Journal, 23(1).
34. Mo, Y., Kang, S. Y., Bang, J. Y., Kim, Y., Jeong, J., Jeong, E. M., . . . Kang, H. R. (2022). Intravenous Mesenchymal Stem Cell Administration Modulates Monocytes/Macrophages and Ameliorates Asthmatic Airway Inflammation in a Murine Asthma Model. Mol Cells, 45(11), 833-845. doi:10.14348/molcells.2022.0038
35. Pomés, A., & Arruda, L. K. (2023). Cockroach allergy: understanding complex immune responses to develop novel therapies. Molecular Immunology, 156, 157-169.doi:10.1016/j.molimm.2023.03.001
36. Rahbarghazi, R., Keyhanmanesh, R., Aslani, M. R., Hassanpour, M., & Ahmadi, M. (2019). Bone marrow mesenchymal stem cells and condition media diminish inflammatory adhesion molecules of pulmonary endothelial cells in an ovalbumin-induced asthmatic rat model. Microvascular Research, 121, 63-70. doi:10.1016/j.mvr.2018.10.005
37. Ren, J., Liu, Y., Yao, Y., Feng, L., Zhao, X., Li, Z., & Yang, L. (2021). Intranasal delivery of MSC-derived exosomes attenuates allergic asthma via expanding IL-10 producing lung interstitial macrophages in mice. International Immunopharmacology, 91, 107288.doi:10.1016/j.intimp.2020.107288
38. Rostamabadi, H., Chaudhary, V., Chhikara, N., Sharma, N., Nowacka, M., Demirkesen, I., . . . Falsafi, S. R. (2023). Ovalbumin, an outstanding food hydrocolloid: Applications, technofunctional attributes, and nutritional facts, A systematic review. Food Hydrocolloids, 139, 108514. doi:https://doi.org/10.1016/j.foodhyd.2023.108514.
39. Royce, S. G., Shen, M., Patel, K. P., Huuskes, B. M., Ricardo, S. D., & Samuel, C. S. (2015). Mesenchymal stem cells and serelaxin synergistically abrogate established airway fibrosis in an experimental model of chronic allergic airways disease. Stem Cell Research, 15(3), 495-505. doi:10.1016/j.scr.2015.09.007
40. Shin, J. W., Ryu, S., Ham, J., Jung, K., Lee, S., Chung, D. H., ... & Kim, H. Y. (2021). Mesenchymal stem cells suppress severe asthma by directly regulating Th2 cells and type 2 innate lymphoid cells. Molecules and Cells, 44(8), 580-590.doi:10.14348/molcells.2021.0101
41. Tang, G. N., Li, C. L., Yao, Y., Xu, Z. B., Deng, M. X., Wang, S. Y., ... & Fu, Q. L. (2016). MicroRNAs involved in asthma after mesenchymal stem cells treatment. Stem Cells and Development, 25(12), 883-896.doi:10.1089/scd.2015.0339
42. Tang, H., Han, X., Li, T., Feng, Y., & Sun, J. (2021). Protective effect of miR‐138‐5p inhibition modified human mesenchymal stem cell on ovalbumin‐induced allergic rhinitis and asthma syndrome. Journal of Cellular and Molecular Medicine, 25(11), 5038-5049. doi:10.1111/jcmm.16473
43. Tortosa-Martínez, J., Beltrán-Carrillo, V. J., Romero-Elías, M., Ruiz-Casado, A., Jiménez-Loaisa, A., & González-Cutre, D. (2023). “To be myself again”: Perceived benefits of group-based exercise for colorectal cancer patients. European Journal of Oncology Nursing, 66, 102405.doi:10.1016/j.ejon.2023.102405
44. Wang, J., Zhao, X., Tian, G., Liu, X., Gui, C., & Xu, L. (2022). Down-regulation of miR-138 alleviates inflammatory response and promotes wound healing in diabetic foot ulcer rats via activating PI3K/AKT pathway and hTERT. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 1153-1163. doi:10.2147/dmso.s359759
45. Wright, D. B., Trian, T., Siddiqui, S., Pascoe, C. D., Ojo, O. O., Johnson, J. R., . . . Kanabar, V. (2013). Functional phenotype of airway myocytes from asthmatic airways. Pulm Pharmacol Ther, 26(1), 95-104. doi:10.1016/j.pupt.2012.08.003
46. Xie, H., Wu, L., Deng, Z., Huo, Y., & Cheng, Y. (2018). Emerging roles of YAP/TAZ in lung physiology and diseases. Life Sciences, 214, 176-183. doi:https://doi.org/10.1016/j.lfs.2018.10.062.
47. Xu, T., Xian, L.-L., Zhou, Y., Plunkett, B., Cao, X., Wan, M., & Gao, P. (2014). TGF-beta1 Mobilizes Mesenchymal Stem Cells In Allergic Asthma. Journal of Allergy and Clinical Immunology, 133(2, Supplement), AB53. doi:https://doi.org/10.1016/j.jaci.2013.12.212.
48. Yao, Y., Fan, X. L., Jiang, D., Zhang, Y., Li, X., Xu, Z. B., . . . Fu, Q. L. (2018). Connexin 43-Mediated Mitochondrial Transfer of iPSC-MSCs Alleviates Asthma Inflammation. Stem Cell Reports, 11(5), 1120-1135. doi:10.1016/j.stemcr.2018.09.012
49. Yu, H., Zhu, G., Qin, Q., Wang, X., Guo, X., & Gu, W. (2024). Mesenchymal Stromal Cell Therapy Alleviates Ovalbumin-Induced Chronic Airway Remodeling by Suppressing M2 Macrophage Polarization. Inflammation, 47(4), 1298-1312. doi:10.1007/s10753-024-01977-9
50. Zhao, R., Wang, L., Wang, T., Xian, P., Wang, H., & Long, Q. (2022). Inhalation of MSC-EVs is a noninvasive strategy for ameliorating acute lung injury. Journal of Controlled Release, 345, 214-230. doi:https://doi.org/10.1016/j.jconrel.2022.03.025.
51. Zhong, H., Fan, X. L., Fang, S. B., Lin, Y. D., Wen, W., & Fu, Q. L. (2019). Human pluripotent stem cell-derived mesenchymal stem cells prevent chronic allergic airway inflammation via TGF-β1-Smad2/Smad3 signaling pathway in mice. Molecular immunology, 109, 51-57.doi:10.1016/j.molimm.2019.02.017
52. Zhuansun, Y., Du, Y., Huang, F., Lin, L., Chen, R., Jiang, S., & Li, J. (2019). MSCs exosomal miR-1470 promotes the differentiation of CD4+ CD25+ FOXP3+ Tregs in asthmatic patients by inducing the expression of P27KIP1. International Immunopharmacology, 77, 105981.doi:10.1016/j.intimp.2019.105981