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Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://www.sciencedirect.com/science/article/pii/S2214031X21000656?via%3Dihub Background: Osteoarthritis (OA) is a joint disease characterized by cartilage degradation, low-grade synovitis and subchondral bone alterations. In the damaged joint, there is a progressive increase of oxidative stress leading to disruption of chondrocyte homeostasis. The modulation of oxidative stress could control the expression of inflammatory and catabolic mediators involved in OA. We have previously demonstrated that extracellular vesicles (EVs) present in the secretome of human mesenchymal stem cells from adipose tissue (AD-MSCs) exert antiinflammatory and anti-catabolic effects in OA chondrocytes. In the current work, we have investigated whether AD-MSC EVs could regulate oxidative stress in OA chondrocytes as well as the possible contribution of peroxiredoxin 6 (Prdx6). Methods: Microvesicles (MV) and exosomes (EX) were isolated from AD-MSC conditioned medium by differential centrifugation with size filtration. The size and concentration of EVs were determined by resistive pulse sensing. OA chondrocytes were isolated from knee articular cartilage of advanced OA patients. 4-Hydroxynonenal adducts, IL-6 and MMP-13 were determined by enzyme-linked immunosorbent assay. Expression of Prdx6 and autophagic markers was assessed by immunofluorescence and Western blotting. Prdx6 was downregulated in AD-MSCs by transfection with a specific siRNA. Results: MV and to a lesser extent EX significantly reduced the production of oxidative stress in OA chondrocytes stimulated with IL-1β. Treatment with MV resulted in a dramatic upregulation of Prdx6. MV also enhanced the expression of autophagy marker LC3B. We downregulated Prdx6 in AD-MSCs by using a specific siRNA and then MV were isolated. These Prdx6-silenced MV failed to modify oxidative stress and the expression of autophagy markers. We also assessed the possible contribution of Prdx6 to the effects of MV on IL-6 and MMP-13 production. The reduction in the levels of both mediators induced by MV was partly reverted after Prdx6 silencing. Conclusion: Our results indicate that EVs from AD-MSCs regulate the production of oxidative stress in OA chondrocytes during inflammation. Prdx6 may mediate the antioxidant and protective effects of MV. The translational potential of this article: This study gives insight into the protective properties of EVs from AD-MSCs in OA chondrocytes. Our findings support the development of novel therapies based on EVs to prevent or treat cartilage degradation.

Este artículo se encuentra disponible en la siguiente URL: https://www.mdpi.com/2227-9059/9/11/1726 Este artículo pertenece al número especial "Adipose-Derived Mesenchymal Stem Cells, Cell-Based Therapies, and Biomaterials as New Regenerative Strategies". Osteoarthritis (OA) is the most common articular disease in adults and has a current prevalence of 12% in the population over 65 years old. This chronic disease causes damage to articular cartilage and synovial joints, causing pain and leading to a negative impact on patients’ function, decreasing quality of life. There are many limitations regarding OA conventional therapies—pharmacological therapy can cause gastrointestinal, renal, and cardiac adverse effects, and some of them could even be a threat to life. On the other hand, surgical options, such as microfracture, have been used for the last 20 years, but hyaline cartilage has a limited regeneration capacity. In recent years, the interest in new therapies, such as cell-based and cell-free therapies, has been considerably increasing. The purpose of this review is to describe and compare bioregenerative therapies’ efficacy for OA, with particular emphasis on the use of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). In OA, these therapies might be an alternative and less invasive treatment than surgery, and a more effective option than conventional therapies.