Osteoarthritis (OA) is a degenerative joint disease with limited therapeutic options, where inflammation plays a critical role in disease progression. Extracellular vesicles (EV) derived from mesenchymal stromal cells (MSC) have shown potential as a therapeutic approach for OA by modulating inflammation and alleviating degenerative processes in the joint. This study evaluated the therapeutic effects for the treatment of OA of two types of EV—exosomes and matrix-bound nanovesicles (MBV)—both derived from the human umbilical cord MSC (UC-MSC) via differential ultracentrifugation. Different phenotypes of human monocyte-derived macrophages (MDM) were used to study the anti-inflammatory properties of EV in vitro, and the medial meniscectomy-induced rat model of knee osteoarthritis (MMx) was used in vivo. The study found that both EV reduced pro-inflammatory cytokines IL-6 and TNF-α in MDM. However, exosomes showed superior results, preserving the extracellular matrix (ECM) of hyaline cartilage, and reducing synovitis more effectively than MBVs. Additionally, exosomes downregulated inflammatory markers (TNF-α, iNOS) and increased Arg-1 expression in macrophages and synovial fibroblasts, indicating a stronger anti-inflammatory effect. These results suggest UC-MSC exosomes as a promising therapeutic option for OA, with the potential for modulating inflammation and promoting joint tissue regeneration.

Control over endogenous reparative mechanisms is the future of regenerative medicine. The rabbit ear defect is a rare model which allows the observation of the epimorphic regeneration of elastic cartilage. However, the mechanisms of phenotypical restoration of this highly differentiated tissue have not been studied. We modelled circular ear defects of different sizes (4, 6, and 8 mm in diameter) in 12 laboratory rabbits, and observed them during 30, 60, 90, and 120 day periods. Excised tissues were processed and analyzed by standard histological methods and special histochemical reactions for senescence associated-β-galactosidase and lectin markers. We demonstrated that larger defects caused significant elevation of senescence associated-β-galactosidase in chondrocytes. The fullness of epimorphic regeneration of elastic cartilage depended on the activation of cellular senescence and synthesis of elastic fibers. Further investigation into the role of cells with senescence-associated secretory phenotype in damaged tissues can present new targets for controlled tissue regeneration.