Inroduction:The results of experimental and clinical studies in recent years indicate that the transplantation of multipotent mesenchymal stromal cells (MMSCs) is a possible approach for the "restoration" of the immune system of patients with autoimmune diseases, in particular, rheumatoid arthritis. However, the strength and duration of the effect vary greatly, which indicates incomplete correction of the tested parameters, thereby opening up the prospect of improving this method of treatment by choosing dose-time parameters and methods of their administration. The aim of this research was to determine the indices of cellular immunity in animals with adjuvant arthritis and therapy with cryopreserved MMSCs derived from adipose and cartilage tissues. Material and methods: Adjuvant arthritis in male rats was modeled by subplantar administration of Freund's complete adjuvant. On day 7 of modeling, experimental animals were administered with saline (control group) or cryopreserved MMSCs from adipose or cartilaginous tissue locally or generalized. On day 28 after therapy the body weight, spleen index and cellularity, and content of CD3+, CD4+, CD8+, CD4+CD25+ cells in the spleen were determined. Results: In the control group of animals, the inflammation was pronounced, as evidenced by a significant increase in the studied parameters throughout the observation period. The use of cryopreserved MMSCs from adipose and cartilaginous tissues led to the restoration of T regulatory cells (Treg) on day 28. Generalized administration of cells had a more pronounced therapeutic effect compared to the animals with local administration. These data can be used to justify and develop a therapeutic approach to rheumatoid arthritis in clinical practice. Conclusions: Cell therapy with cryopreserved MMSCs from investigated sources provided by both local and generalized administration to animals with adjuvant arthritis has a correcting effect on the cellular immunity.

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.