Impact of the therapy that changes the clinical course of multiple sclerosis using allogeneic mesenchymal stem cell transplantation on the immunological parameters of patients
https://doi.org/10.29235/1814-6023-2023-20-4-299-307
Abstract
Multiple sclerosis (MS) is a multifactorial, autoimmune, chronic disease of the nervous system, manifested by multifocal neurological symptoms and occurring in typical cases in the presence of symptoms of a relapsing course. MS is one of the problems of modern neurology, which is characterized by the prevalence of diseases, the prevalence of patients in the age group from 20 to 40 years, as well as high disability. The main target of therapeutic options in MS is the appearance on the immune system in order to suppress the inflammatory process leading to demyelination. With a set of drugs that allow clinically modifying the course of MS (beta-interferon, glatiramer acetate, fingolimod, etc.), 40 % of patients have a good effect, 40 % have a questionable result, and 20 % of patients with MS do not detect treatment. Lack of treatment protocols aimed at selective stimulatory suppression of autoreactive T-lymphocyte clones and restoration of affected areas of the CNS, weakening of the ever-increasing interest in identifying the immunomodulatory and neuroprotective properties of mesenchymal stem cells (MSCs). From carriers, the benefits of allogeneic versus autologous MSC implantation are widely discussed without the presence of objective evidence of the superiority of one type of cell therapy over the estimated and estimated fees of autologous or allogeneic transplants in obtaining MS remains controversial.
Objective ‒ to study the effect of modifying therapy using allogeneic mesenchymal stromal stem cells on the immunological parameters of patients with multiple sclerosis.
The results of assessing the dynamics of a number of immunological biomarkers in 4 patients with relapsing-remitting MS. All patients are men. The median age is 35.0 + 11.4 years. At the screening period, the Expanded Disability Status Scale (EDSS) score was 3.6 [2.5; 6.0]. immunological and cellular-morphological parameters of MSC cultures were revealed, enhanced due to adipose tissue (AT) of 7 donors. Of the 7 samples of AT MSCs, 2 samples were selected with the highest coefficients of suppression of T-lymphocyte proliferation, of which 4 biomedical cell products should be taken for therapy.
In patients with MS, the most significant changes were observed by 6 months of the post-transplantation period and were characterized by a decrease in γIFN production, the number of functions of immature “double positive” and “double negative” T-lymphocytes, and a decrease in the cytotoxic orientation of T-lymphocytes with a γδ T-cell receptor characterized by characteristics of an increase in the number of cells expressing CD45RO+ (memory cell marker) in an increase with a decrease in the number of γδTCR CD314+ lymphocytes (expressive key activator of killer receptors).
Preliminary results from a study of transplantation of alloMSCs to the immunological status of MS patients suggest that they accept disease-modifying therapy in this application as pathogenetic, disease-modifying therapy.
About the Authors
A. S. FedulovBelarus
Alexander S. Fedulov ‒ D. Sc. (Med.), Professor, Head of the Department. Belarusian State Medical University.
83, Dzerzhinski Ave., 220116, Minsk
M. M. Zafranskaya
Belarus
Marina M. Zafranskaya ‒ D. Sc. (Med.), Associate Professor, Leading Researcher, Belarusian Medical Academy of Postgraduate Education.
3/3, P. Browka Str., 220013, Minsk
A. V. Borisov
Belarus
Alexey V. Borisov ‒ D. Sc. (Med.), Professor. Belarusian State Medical University.
83, Dzerzhinski Ave., 220116, Minsk
D. B. Nizhegorodova
Belarus
Daria B. Nizhegorodova ‒ Ph. D. (Biol.), Leading Researcher, Belarusian Medical Academy of Postgraduate Education.
3/3, P. Browka Str., 220013, Minsk
N. A. Volkova
Belarus
Natalia A. Volkova ‒ Assistant, Belarusian State Medical University.
83, Dzerzhinski Ave., 220116, Minsk
S. I. Krivenko
Belarus
Svetlana I. Krivenko ‒ D. Sc. (Med.), Professor, Chief Researcher, Deputy Director, Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology.
8, Semashko Str., 220045, Minsk
T. A. Shalukho
Belarus
Tina A. Shalukho ‒ Assistant, Belarusian State Medical University.
83, Dzerzhinski Ave., 220116, Minsk
References
1. Fedulov A. S., Borisov A. V., Zafranskaya M. M., Marchenko L. N., Krivenko S. I., Kachan T. V., Dalidovich A. A. Cell Therapy for Multiple Sclerosis. Minsk, NiktagrafiksPlyus Publ., 2018. 242 p. (in Russian).
2. Fedulov A. S., Borisov A. V., Zafranskaya M. M., Krivenko S. I., Marchenko L. N., Kachan T. V., Moskovskikh Yu. V., Nizhegorodova D. B. Comparative evaluation of the efficiency of single and course use of autologous mesenchymal stem cell transplantation in the treatment of multiple sclerosis. RMZh. Meditsinskoe obozrenie [RMJ. Medical review], 2019, vol. 3, no. 4–2, pp. 54–58 (in Russian).
3. Gugliandolo А., Bramanti P., Mazzon E. Mesenchymal Stem Cells in Multiple Sclerosis: Recent Evidence from Pre-Clinical to Clinical Studies. International Journal of Molecular Sciences, 2020, vol. 21, no. 22, art. 8662. https://doi.org/10.3390/ijms21228662
4. Karussis D., Karageorgiou C., Vaknin-Dembinsky A., Gowda-Kurkalli B., Gomori J. M., Kassis I. [et al.]. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Archives of Neurology, 2010, vol. 67, no. 10, pp. 1187–1194. https://doi.org/10.1001/archneurol.2010.248
5. Mansilla M. J., Presas-Rodríguez S., Teniente-Serra A., González-Larreategui I., Quirant-Sánchez B., Fondelli F. [et al.]. Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy. Cellular & Molecular Immunology, 2021, vol. 18, no. 6, pp. 1353–1374. https://doi.org/10.1038/s41423-020-00618-z
6. Zafranskaya M. M., Fedulov A. S., Demidchik Yu. E. The effect of mesenchymal stem cells in cell therapy of multiple sclerosis. Minsk, Belaruskaya navuka Publ., 2016. 213 p. (in Russian).
7. Darlington P. J., Boivin M. N., Bar-Or A. Harnessing the therapeutic potential of mesenchymal stem cells in multiple sclerosis. Expert Review of Neurotherapeutics, 2011, vol. 11, no. 9, pp. 1295–1303. https://doi.org/10.1586/ern.11/113
8. Mallam E., Kemp K., Wilkins A., Rice C., Scolding N. Characterization of in vitro expanded bone marrow-derived mesenchymal stem cells from patients with multiple sclerosis. Multiple Sclerosis, 2010, vol. 16, no. 8, pp. 909–918. https://doi.org/10.1177/1352458510371959
9. Zafranskaya M. M., Nizhegorodova D. B., Yurkevich M. Yu., Borisov A. V., Krivenko S. I., Ivanchik G. I., Kulinich S. S., Fedulov A. S. Immunological monitoring of patients with multiple sclerosis after autologous mesenchymal stem cell transplantation. Immunologiya [Immunology], 2015, vol. 36, no. 5, pp. 284–289 (in Russian).
10. Fedulov A. S., Zafranskaya M. M., Motuzova Ya. M., Nizhegorodova D. B., Krivenko S. I., Borisov A. V. [et al.]. Method of cell therapy for multiple sclerosis: instructions for use: approved by the Ministry of Health of the Republic of Belarus on December 27, 2013. Minsk, 2013. 11 p. (in Russian).
11. Stojanovic A., Correia M. P., Cerwenka A. The NKG2D/NKG2DL Axis in the Crosstalk Between Lymphoid and Myeloid Cells in Health and Disease. Frontiers in Immunology, 2018, vol. 9, art. 827. https://doi.org/10.3389/fimmu.2018.00827
12. Auletta J. J., Deans R. J., Bartholomew A. M. Emerging roles for multipotent, bone marrow-derived stromal cells in host defense. Blood, 2012, vol. 119, no. 8, pp. 1801–1809. https://doi.org/10.1182/blood-2011-10-384354
Review
For citations:
Fedulov A.S., Zafranskaya M.M., Borisov A.V., Nizhegorodova D.B., Volkova N.A., Krivenko S.I., Shalukho T.A. Impact of the therapy that changes the clinical course of multiple sclerosis using allogeneic mesenchymal stem cell transplantation on the immunological parameters of patients. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2023;20(4):299-307. (In Russ.) https://doi.org/10.29235/1814-6023-2023-20-4-299-307