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.
Highlights
The problem of rheumatic diseases management is relevant worldwide
According to the authors (Fu et al, 2017; Volkova et al, 2019; Jimenez-Puerta et al, 2020) mesenchymal stromal cells (MMSCs) can promote regeneration by direct cell differentiation and by secretion of biologically active substances known as growth factors
It should be noted that the regulators of prochondrogenic cells and direct chondrogenic differentiation are a number of intracellular signaling molecules and growth factors, which include fibroblast growth factor (FGF), bone morphogenetic protein (BMP), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF), epidermal factor (Jafri et al, 2020; Qasim et al, 2020)
Summary
According to the World Health Organization, in the developed countries of the world inflammatory diseases of the joints and connective tissue occupy the second place after cardiovascular pathology among the causes of disability and mortality. Rheumatoid arthritis is characterized by autoimmune chronic inflammatory synovitis with progressive joint destruction and a wide range of extra-articular (systemic) manifestations (Rana et al, 2018). Its genetic and metabolic impairments contribute greatly to pathogenesis of some pathologies, including rheumatoid arthritis (Phull et al, 2018). Against this background there was noted an infiltration of synovial membrane with lymphocytes, monocytes, plasmatic cells, which under co-operative interaction release the mediators, provoking an inflammatory reaction and destruction of tissues
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