Abstract
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.
Highlights
Articular cartilage defect (ACD) is a common clinical disease, which can be induced by trauma, joint degeneration, infection, autoimmune diseases, and among other reasons
The results showed that long non-coding RNAs (LncRNAs) PCGEM1 [a sponge IncRNA targeting miR-770 and motivating the propagation of osteoarthritic synoviocytes (Kang et al, 2016)] expression in synovial fluid was significantly higher in early primary OA (KL scale 0–2, 2:16:2) and late primary OA (KL scale 1–4, 1:3:15:3) compared to controls (KL scale 0–1, 18:2), which in turn was higher in late OA than in early OA
The results indicated that the isolated exosomes facilitated the proliferation and migration of chondrocytes and maintained the homeostasis of chondrocyte matrix, and suppressed the infiltration of M1 macrophages into synovium, preventing cartilage degeneration and delaying the progression of OA
Summary
Articular cartilage defect (ACD) is a common clinical disease, which can be induced by trauma, joint degeneration, infection, autoimmune diseases, and among other reasons. The release and formation of exosomes are regulated by some lipid metabolic enzymes, such as phospholipase D2 (PLD2) or neutral sphingomyelinase (nSMase) (Bjorge et al, 2017; Mianehsaz et al, 2019) Those bioactive lipids cargo within EVs derived from stem cells have a variety of signal transduction functions, including immunomodulatory and anti-inflammatory activities (Bjorge et al, 2017). Ultracentrifugation Ultracentrifugation is the most commonly used technique for the isolation of EVs and a traditional method developed by Johnstone et al to pellet the vesicles, which involves the separation of cells by centrifugation followed by the recentrifugation of the supernatant in 100,000 g for 90 min (Bjorge et al, 2017) This method is suitable for the granulation of lipoproteins, extracapsular protein complexes, aggregates, and other pollutants but not suitable for isolating exosomes for clinical samples because it is time-consuming and laborious.
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