Course correction of adjuvant arthritis with cryopreserved multipotent mesenchymal stromal cells

  • D. B. Vvedenskyi Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine
  • N. O. Volkova Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine
  • M. S. Yukhta Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine
  • N. O. Ashukina Sytenko Institute of Spine and Joint Pathology National Academy of Medical Sciences of Ukraine
  • A. M. Goltsev Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine
Keywords: cell therapy; cartilage; adipose tissue; method of administration; rats

Abstract

Rheumatoid arthritis is an inflammatory autoimmune disease that occurs as a result of impaired immune tolerance, leading to an aberrant immune response to autologous antigens. Multipotent mesenchymal stromal cells (MMSCs) and the biologically active substances they produce can promote the activation of regenerative processes in the organism not only by direct cell differentiation, but also due to their inherent trophic and immunosuppressive potentials. The aim of the study was to experimentally evaluate changes in the course of the acute phase of adjuvant arthritis upon local and generalized administration of cryopreserved MMSCs from adipose and cartilage tissues. The results of histological, imunohistochemical and biochemical studies showed that the animals of the control group throughout the observation period developed an inflammatory process, which manifested in joint swelling (increased arthritis index), leukocytosis, spread of chondrocyte-free zones, weakening of staining, loss of clarity of cartilage tissue contours, increased content of cyclooxygenase-2, reduced glycosaminoglycan content and total antioxidant defense system activity. At the same time, the local administration of cryopreserved MMSCs from adipose and cartilage tissues contributed to the normalization of the structural and functional organization, content of glycosaminoglycans and cyclooxygenase-2 with complete recovery of blood parameters. Less pronounced regeneration processes in articular cartilage occurred under generalized administration of cryopreserved MMSCs from adipose and cartilage tissues in comparison with the local method. However, the difference between the control and experimental groups indicates the ability of cryopreserved MMSCs to influence the intensity of regenerative processes in damaged cartilage tissue with both methods of administration. Comparative evaluation of the use of cryopreserved MMSCs from adipose and cartilage tissues showed the absence of significant changes in the studied indicators. These data can be used to substantiate and develop methods of arthritis treatment in clinical practice.

References

Bhakta, S., Hong, P., & Koc, O. (2006). The surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell-derived factor-1 in vitro but does not decrease apoptosis under serum deprivation. Cardiovascular Revascularization Medicine, 7(1), 19–24.

Bullock, J., Rizvi, S., Saleh, A. M., Ahmed, S. S., Do, D. P., Ansari, R. A., & Ahmed, J. (2018). Rheumatoid arthritis: A brief overview of the treatment. Medical Principles and Practice, 27(6), 501–507.

Burmester, G. R., & Pope, J. E. (2017). Novel treatment strategies in rheumatoid arthritis. Lancet, 389(10086), 2338–2348.

Chen, K., Bao, Z., Tang, P., Gong, W., Yoshimura, T., & Wang, J. M. (2018). Chemokines in homeostasis and diseases. Cellular and Molecular Immunology, 15(4), 324–334.

Choudhary, N., Bhatt, L. K., & Prabhavalkar, K. S. (2018). Experimental animal models for rheumatoid arthritis. Immunopharmacology and Immunotoxicology, 40(3), 193–200.

Conigliaro, P., Triggianese, P., De Martino, E., Fonti, G. L., Chimenti, M. S., Sunzini, F., Viola, A., Canofari, C., & Perricone, R. (2019). Challenges in the treatment of Rheumatoid Arthritis. Autoimmunity Reviews, 18(7), 706–713.

Dey, P. (2018). Basic and advanced laboratory techniques in histopathology and cytology. Springer, Singapore.

Fan, X. L., Zhang, Y., Li, X., & Fu, Q. L. (2020). Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cellular and Molecular Life Sciences, 77(14), 2771–2794.

Fitzsimmons, R., Mazurek, M. S., Soos, A., & Simmons, C. A. (2018). Mesenchymal stromal/stem cells in regenerative medicine and tissue engineering. Stem Cells International, 2018, 8031718.

Freitag, J., Bates, D., Boyd, R., Shah, K., Barnard, A., Huguenin, L., & Tenen, A. (2016). Mesenchymal stem cell therapy in the treatment of osteoarthritis: Reparative pathways, safety and efficacy – a review. BMC Musculoskeletal Disorders, 17, 230.

Freyria, A. M., & Mallein-Gerin, F. (2012). Chondrocytes or adult stem cells for cartilage repair: The indisputable role of growth factors. Injury, 43(3), 259–265.

Fu, X., Liu, G., Halim, A., Ju, Y., Luo, Q., & Song, A. G. (2019). Mesenchymal stem cell migration and tissue repair. Cells, 8(8), 784.

Fu, Y., Karbaat, L., Wu, L., Leijten, J., Both, S. K., & Karperien, M. (2017). Trophic effects of mesenchymal stem cells in tissue regeneration. Tissue Engineering. Part B, Reviews, 23(6), 515–528.

Gerwin, N., Bendele, A. M., Glasson, S., & Carlson, C. S. (2010). The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the rat. Osteoarthritis and Cartilage, 18(S3), S24–S34.

Goryachev, D. V., & Telnykh, M. Y. (2018). Planirovanie registracionnoj programmy issledovanij preparatov bazisnoj protivovospalitel'noj terapii revmatoidnogo artrita [Planning of a clinical data registry for basic anti-inflammatory drugs for the treatment of rheumatoid arthritis]. The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products, 8(4), 238–245 (in Russian).

Ingawale, D. K., & Patel, S. S. (2018). Hecogenin exhibits anti-arthritic activity in rats through suppression of pro-inflammatory cytokines in Complete Freund’s adjuvant-induced arthritis. Immunopharmacology and Immunotoxicology, 40(1), 59–71.

Jafri, M. A., Kalamegam, G., Abbas, M., Al-Kaff, M., Ahmed, F., Bakhashab, S., Rasool, M., Naseer, M. I., Sinnadurai, V., & Pushparaj, P. N. (2020). Deciphering the association of cytokines, chemokines, and growth factors in chondrogenic differentiation of human bone marrow mesenchymal stem cells using an ex vivo osteochondral culture system. Frontiers in Cell and Developmental Biology, 7, 380.

Jimenez-Puerta, G. J., Marchal, J. A., López-Ruiz, E., & Gálvez-Martín, P. (2020). Role of mesenchymal stromal cells as therapeutic agents: Potential mechanisms of action and implications in their clinical use. Journal of Clinical Medicine, 9(2), 445.

Kangari, P., Talaei-Khozani, T., Razeghian-Jahromi, I., & Razmkhah, M. (2020). Mesenchymal stem cells: Amazing remedies for bone and cartilage defects. Stem Cell Research and Therapy, 11(1), 492.

Kim, Y. K., Na, K. S., Myint, A. M., & Leonard, B. E. (2016). The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 64, 277–284.

Le, H., Xu, W., Zhuang, X., Chang, F., Wang, Y., & Ding, J. (2020). Mesenchymal stem cells for cartilage regeneration. Journal of Tissue Engineering, 11, 2041731420943839.

Levato, R., Webb, W. R., Otto, I. A., Mensinga, A., Zhang, Y., van Rijen, M., van Weeren, R., Khan, I. M., & Malda, J. (2017). The bio in the ink: Cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells. Acta Biomaterialia, 61, 41–53.

Li, X., Wang, M., Jing, X., Guo, W., Hao, C., Zhang, Y., Gao, S., Chen, M., Zhang, Z., Zhang, X., Shen, S., Zhang, B., Xian, H., Wang, Z., Wang, Y., Sui, X., Wang, A., Peng, J., Lu, S., Liu, S., & Guo, Q. (2018). Bone marrow- and adipose tissue-derived mesenchymal stem cells: Characterization, differentiation, and applications in cartilage tissue engineering. Critical Reviews in Eukaryotic Gene Expression, 28(4), 285–310.

Neybecker, P., Henrionnet, C., Pape, E., Grossin, L., Mainard, D., Galois, L., Loeuille, D., Gillet, P., & Pinzano, A. (2020). Respective stemness and chondrogenic potential of mesenchymal stem cells isolated from human bone marrow, synovial membrane, and synovial fluid. Stem Cell Research and Therapy, 11(1), 316.

Peng, L., Jia, Z., Yin, X., Zhang, X., Liu, Y., Chen, P., Ma, K., & Zhou, C. (2008). Comparative analysis of mesenchymal stem cells from bone marrow, cartilage, and adipose tissue. Stem Cells and Development, 17(4), 761–773.

Phull, A. R., Nasir, B., ul Haq, I., & Kim, S. J. (2018). Oxidative stress, consequences and ROS mediated cellular signaling in rheumatoid arthritis. Chemico-Biological Interactions, 281, 121–136.

Qasim, M., Chae, D. S., & Lee, N. Y. (2020). Bioengineering strategies for bone and cartilage tissue regeneration using growth factors and stem cells. Journal of Biomedical Materials Research, Part A, 108(3), 394–411.

Rana, A. K., Li, Y., Dang, Q., & Yang, F. (2018). Monocytes in rheumatoid arthritis: Circulating precursors of macrophages and osteoclasts and, their heterogeneity and plasticity role in RA pathogenesis. International Immunopharmacology, 65, 348–359.

Sasaki, A., Mizuno, M., Mochizuki, M., & Sekiya, I. (2019). Mesenchymal stem cells for cartilage regeneration in dogs. World Journal of Stem Cells, 11(5), 254–269.

Savvidou, O., Milonaki, M., Goumenos, S., Flevas, D., Papagelopoulos, P., & Moutsatsou, P. (2019). Glucocorticoid signaling and osteoarthritis. Molecular and Cellular Endocrinology, 480, 153–166.

To, K., & Khan, W. (2019). Mesenchymal stem cell transplantation in rheumatoid arthritis. In: Pham, P. (Ed.). Stem cells in clinical applications. Springer, Cham.

Volkova, N. A., & Goltsev, A. N. (2015). Cryopreservation effect on proliferation and differentiation potential of cultured chorion cells. Cryo Letters, 36(1), 25–29.

Volkovа, N. A., Yukhta, M. S., & Goltsev, A. N. (2016). Morphological and functional characteristics of cryopreserved multipotent mesenchymal stromal cells from bone marrow, adipose tissue and tendons. Cell and Organ Transplantology, 4(2), 200–205.

Volkovа, N. A., Yukhta, M. S., & Goltsev, A. N. (2019). Influence of growth factors on cryopreserved mesenchymal stromal cells. Fiziolohichnyi Zhurnal, 65(2), 12–21 (in Ukrainian).

Wassmer, C. H., & Berishvili, E. (2020). Immunomodulatory properties of amniotic membrane derivatives and their potential in regenerative medicine. Current Diabetes Reports, 20(8), 31.

Zhang, F., & Ma, C. (2018). Comparison of the effectiveness on intra-articular and subcutaneous TNF inhibitor in rheumatoid arthritis patients. Clinical Rheumatology, 37(1), 199–204. 

Published
2021-08-06
How to Cite
Vvedenskyi, D. B., Volkova, N. O., Yukhta, M. S., Ashukina, N. O., & Goltsev, A. M. (2021). Course correction of adjuvant arthritis with cryopreserved multipotent mesenchymal stromal cells . Regulatory Mechanisms in Biosystems, 12(3), 545-553. https://doi.org/10.15421/022175

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