Immunomodulatory effect of cell therapy on the experimental inflammatory bowel disease model
https://doi.org/10.29235/1814-6023-2021-18-2-177-185
Abstract
Dysregulation of innate and adaptive immunity is a central mechanism in the pathogenesis of inflammatory bowel diseases (IBD) that include Crohn’s disease (CD) and ulcerative colitis (UC). Given the immunomodulatory properties of multipotent mesenchymal stromal cells (MMSCs), developing new pathogenetic approaches to the IBD treatment using cell therapy seems to be promising.
In this article, the effect of intra-arterial and intravenous MMSCs on in vitro monocytes/macrophages cytokine-producing function and splenocytes proliferative activity in laboratory animals with experimental IBD under the conditions of nonspecific and specific stimulation (mannan – cell wall component of Saccharomyces cerevisiae yeast) was studied.
MMSC cultures have been shown to possess an immunomodulatory effect against the background of improved clinical, morphometric parameters, and the pathomorphological picture of experimental IBD damage. Intra-arterial and intravenous administration of cell cultures decreased the mannan-induced TNF-α production by CD68+ cells and mitogen/mannan-stimulated splenocyte proliferation that confirms the immunosuppressive effect of MMSC cultures on autoreactive splenocyte clones in experimental IBD. The obtained results testify to the anti-inflammatory effect of cell therapy in the experimental modeling of IBD and justified a combined administration of MMSC cultures.
About the Authors
H. Y. AdamovichBelarus
Hanna Yu. Adamovich ‒ Junior Researcher
3/3, P. Browka Str., 220013, Minsk
D. B. Nizheharodava
Belarus
Darya B. Nizheharodava ‒ Ph. D. (Biol.), Leading Researcher, Head of the Department
3/3, P. Browka Str., 220013, Minsk
V. K. Shadryna
Belarus
Viktoriya K. Shadrina ‒ Junior Researcher
3/3, P. Browka Str., 220013, Minsk
A. G. Dybau
Belarus
Aleh G. Dybau ‒ Postgraduate student
3/3, P. Browka Str., 220013, Minsk
A. M. Starastsin
Belarus
Andrei M. Starastin ‒ Postgraduate student
3/3, P. Browka Str., 220013, Minsk
T. E. Vladimirskaya
Belarus
Tat’yana E. Vladimirskaya ‒ Ph. D. (Biol.), Leading Researcher, Head of the Department
3/3, P. Browka Str., 220013, Minsk
A. U. Varabei
Belarus
Aliaksandr U. Varabei ‒ Corresponding Member, D. Sc. (Med.), Professor, Head of the Department
3/3, P. Browka Str., 220013, Minsk
M. М. Zafranskayа
Belarus
Marina M. Zafranskaya ‒ D. Sc. (Med.), Associate Professor, Head of the Department
23/1, Dolgobrodskaya Str., 220070, Minsk
References
1. Zafranskaya M. M., Adamovich A. Yu., Vorobei A. V., Starostin A. M., Nizhegorodova D. B. Phenotypic peripheral blood lymphoid cells profile in patients with inflammatory bowel diseases. Meditsinskaya immunologiya [Medical immunology], 2020, vol. 22, no. 6, pp. 1131–1140 (in Russian).
2. Tkachev A. V., Mkrtchyan L. S., Nikitina K. E., Volynskaya E. I. Inflammatory bowel disease: crossing of the problems. Prakticheskaya meditsina [Practical medicine], 2012, vol. 3, no. 58, pp. 17–22 (in Russian).
3. Danese S., Fiocchi C. Etiopathogenesis of inflammatory bowel diseases. World Journal of Gastroenterology, 2006, vol. 12, no. 30, pp. 4807–4812. https://doi.org/10.3748/wjg.12.4807
4. Ocansey D. K. W., Qiu W., Wang J., Yan Y., Qian H., Zhang X., Xu W., Mao F. The achievements and challenges of mesenchymal stem cell-based therapy in inflammatory bowel disease and its associated colorectal cancer. Stem Cells International, 2020, vol. 2020, art. ID 7819824. https://doi.org/10.1155/2020/7819824
5. Ahluwalia B., Moraes L., Magnusson M. K., Öhman L. Immunopathogenesis of inflammatory bowel disease and mechanisms of biological therapies. Scandinavian Journal of Gastroenterology, 2018, vol. 53, no. 4, pp. 379–389. https://doi.org/10.1080/00365521.2018.1447597
6. Grégoire C., Lechanteur C., Briquet A., Baudoux É., Baron F., Louis E., Beguin Y. Review article: mesenchymal stromal cell therapy for inflammatory bowel diseases. Alimentary Pharmacology and Therapeutics, 2017, vol. 45, no. 2, pp. 205–221. https://doi.org/10.1111/apt.13864
7. Kang J., Zhang L., Luo X., Ma X., Wang G., Yang Y. [et al.]. Systematic exposition of mesenchymal stem cell for inflammatory bowel disease and its associated colorectal cancer. BioMed Research International, 2018, vol. 2018, art. ID 9652817. https://doi.org/10.1155/2018/9652817
8. Kim D. H., Cheon J. H. Pathogenesis of inflammatory bowel disease and recent advances in biologic therapies. Immune Network, 2017, vol. 17, no. 1, pp. 25–40. https://doi.org/10.4110/in.2017.17.1.25
9. Guan Q. A comprehensive review and update on the pathogenesis of inflammatory bowel disease. Journal of Immunology Research, 2019, vol. 2019, art. ID 7247238. https://doi.org/10.1155/2019/7247238
10. Ocansey D. K. W., Wang L., Wang J., Yan Y., Qian H., Zhang X., Xu W., Mao F. Mesenchymal stem cell-gut microbiota interaction in the repair of inflammatory bowel disease: an enhanced therapeutic effect. Clinical and Translational Medicine, 2019, vol. 8, no. 31, pp. 1–17. https://doi.org/10.1186/s40169-019-0251-8
11. Adamovich A. Yu., Dybov O. G., Starostin A. M., Vanslav M. I., Ignatovich T. V., Nizhegorodova D. B. Experimental modeling IBD in vivo. Koloproktologiya [Koloproctology], 2019, vol. 18, no. 3 (suppl.), p. 78 (in Russian).
12. Adamovich A. Yu., Dybov O. G., Starostin A. M., Ignatovich T. V. Experimental model of inflammatory bowel disease. Sovremennye problemy infektsionnoi patologii cheloveka: sbornik nauchnykh trudov [Modern problems of infectious human pathology: collection of scientific papers]. Minsk, 2019, no. 12, pp. 206–207 (in Russian).
13. Zafranskaya M. M., Fedulov A. S., Nizhegorodova D. B., Motuzova Ya. M., Kolobova M. Yu., Bagatka S. S., Milanovich N. F., Ivanchik G. I. Influence of mesenchymal stem cells on the memory T-cells proliferation in patients with multiple sclerosis. Vestsі Natsyyanal’nai akademіі navuk Belarusі. Seryya meditsinskіkh navuk = Proceedings of the National Academy of Sciences of Belarus. Medical series, 2010, no. 3, pp. 24–31 (in Russian).
14. Zafranskaya M. M., Nizhegorodova D. B., Kondratovich T. V., Yurkevich M. Yu., Komissarov K. S., Ivanchik G. I., Kulinich S. S., Pilotovich V. S. Influence of bone marrow mononuclear cells and mesenchymal stem cells on the splenocyte proliferation of rats in vitro. Vestsі Natsyyanal’nai akademіі navuk Belarusі. Seryya meditsinskikh navuk = Proceedings of the National Academy of Sciences of Belarus. Medical series, 2015, no. 4, pp. 30–37 (in Russian).
15. Seibold F., Boldt A. B. W., Seibold-Schmid B., Schoepfer A. M., Flogerzi B., Müller S., Kun J. F. J. Association of deficiency for mannan-binding lectin with antimannan antibodies in Crohn’s disease: a family study. Inflammatory Bowel Diseases, 2007, vol. 13, no. 9, pp. 1077–1082. https://doi.org/10.1002/ibd.20156
Review
For citations:
Adamovich H.Y., Nizheharodava D.B., Shadryna V.K., Dybau A.G., Starastsin A.M., Vladimirskaya T.E., Varabei A.U., Zafranskayа M.М. Immunomodulatory effect of cell therapy on the experimental inflammatory bowel disease model. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2021;18(2):177-185. (In Russ.) https://doi.org/10.29235/1814-6023-2021-18-2-177-185