Diagnostic and Therapeutic Role of Extracellular Vesicles in Articular Cartilage Lesions and Degenerative Joint Diseases.

Two leading contributors to the global disability are cartilage lesions and degenerative joint diseases, which are characterized by the progressive cartilage destruction. Current clinical treatments often fail due to variable outcomes and an unsatisfactory long-term repair. Cell-based therapies were once considered as an effective solution because of their anti-inflammatory and immunosuppression characteristics as well as their differentiation capacity to regenerate the damaged tissue. However, stem cell-based therapies have inherent limitations, such as a high tumorigenicity risk, a low retention, and an engraftment rate, as well as strict regulatory requirements, which result in an underwhelming therapeutic effect. Therefore, the non-stem cell-based therapy has gained its popularity in recent years. Extracellular vesicles (EVs), in particular, like the paracrine factors secreted by stem cells, have been proven to play a role in mediating the biological functions of target cells, and can achieve the therapeutic effect similar to stem cells in cartilage tissue engineering. Therefore, a comprehensive review of the therapeutic role of EVs in cartilage lesions and degenerative joint diseases can be discussed both in terms of time and favorability. In this review, we summarized the physiological environment of a joint and its pathological alteration after trauma and consequent changes in EVs, which are lacking in the current literature studies. In addition, we covered the potential working mechanism of EVs in the repair of the cartilage and the joint and also discussed the potential therapeutic applications of EVs in future clinical use.