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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.

[EN] Mesenchymal stem/stromal cells (MSCs) represent a promising therapy for musculoskeletal diseases. There is compelling evidence indicating that MSC effects are mainly mediated by paracrine mechanisms and in particular by the secretion of extracellular vesicles (EVs). Many studies have thus suggested that EVs may be an alternative to cell therapy with MSCs in tissue repair. In this review, we summarize the current understanding of MSC EVs actions in preclinical studies of (1) immune regulation and rheumatoid arthritis, (2) bone repair and bone diseases, (3) cartilage repair and osteoarthritis, (4) intervertebral disk degeneration and (5) skeletal muscle and tendon repair. We also discuss the mechanisms underlying these actions and the perspectives of MSC EVs-based strategies for future treatments of musculoskeletal disorders., This work has been funded by grant SAF2017-85806-R (Ministerio de Ciencia, Innovación y Universidades, Spain, FEDER.

Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194752 The goal of this study was to objectively assess the effect of a platelet-rich plasma (PRP) derivate in English bulldogs with stifle degenerative joint disease secondary to cranial cruciate ligament rupture (CCLR). We used a force platform and affixed electrogoniometers to measure peak vertical force (PVF), vertical impulse (VI), stance time (ST), and angular range of motion (AROM), from 12 lame client-owned English bulldogs with post-CCLR stifle joint abnormalities. The 12 affected subjects were treated with 4 intra-articular injections of PRP, at 30-day intervals. Ten untreated, sound English bulldogs were used as a reference group. Clinical outcomes were evaluated using a linear mixed effects model. Mean values of PVF, VI, ST, and AROM were improved within the first 3 months post-treatment in the CCLR group, with mean measured changes increasing to maximum 4.56% body weight gain, 1.5% body weight/second, 0.07 seconds, and 6.18 degrees, respectively. The effects declined progressively after the treatment interval, ending at nearly initial levels after 6 months. This study demonstrates that dogs with CCLR treated with intra-articular PRP had improved PVF, VI, ST, and AROM over time; the duration of effect was waning by the end of the post-treatment period.

et al., [Background]: Osteoarthritis is the most prevalent joint disease and a frequent cause of joint pain, functional loss, and disability. Osteoarthritis often becomes chronic, and conventional treatments have demonstrated only modest clinical benefits without lesion reversal. Cell-based therapies have shown encouraging results in both animal studies and a few human case reports. We designed a pilot study to assess the feasibility and safety of osteoarthritis treatment with mesenchymal stromal cells (MSCs) in humans and to obtain early efficacy information for this treatment. [Methods]: Twelve patients with chronic knee pain unresponsive to conservative treatments and radiologic evidence of osteoarthritis were treated with autologous expanded bone marrow MSCs by intra-articular injection (40×10 cells). Clinical outcomes were followed for 1 year and included evaluations of pain, disability, and quality of life. Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping. [Results]: Feasibility and safety were confirmed, and strong indications of clinical efficacy were identified. Patients exhibited rapid and progressive improvement of algofunctional indices that approached 65% to 78% by 1 year. This outcome compares favorably with the results of conventional treatments. Additionally, quantification of cartilage quality by T2 relaxation measurements demonstrated a highly significant decrease of poor cartilage areas (on average, 27%), with improvement of cartilage quality in 11 of the 12 patients. [Conclusions]: MSC therapy may be a valid alternative treatment for chronic knee osteoarthritis. The intervention is simple, does not require hospitalization or surgery, provides pain relief, and significantly improves cartilage quality.

Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://www.mdpi.com/1422-0067/19/7/1926 Osteoarthritis (OA) is a major cause of disability in elderly population around the world. More than one-third of people over 65 years old shows either clinical or radiological evidence of OA. There is no effective treatment for this degenerative disease, due to the limited capacity for spontaneous cartilage regeneration. Regarding the use of regenerative therapies, it has been reported that one option to restore degenerated cartilage are adipose-derived mesenchymal stem cells (ASCs). The purpose of this review is to describe and compare the efficacy of ASCs versus other therapies in OA. Methods: Recent studies have shown that ASCs exert paracrine effects protecting against degenerative changes in chondrocytes. According to the above, we have carried out a review of the literature using a combination of osteoarthritis, stem cells, and regenerative therapies as keywords. Results: Conventional pharmacological therapies for OA treatment are considered before the surgical option, however, they do not stop the progression of the disease. Moreover, total joint replacement is not recommended for patients under 55 years, and high tibia osteotomy (HTO) is a viable solution to address lower limb malalignment with concomitant OA, but some complications have been described. In recent years, the use of mesenchymal stem cells (MSCs) as a treatment strategy for OA is increasing considerably, thanks to their capacity to improve symptoms together with joint functionality and, therefore, the patients’ quality of life. Conclusions: ASC therapy has a positive effect on patients with OA, although there is limited evidence and little long-term follow-up.

et al., [Background]: Osteoarthritis is the most prevalent joint disease and a frequent cause of joint pain, functional loss, and disability. Osteoarthritis often becomes chronic, and conventional treatments have demonstrated only modest clinical benefits without lesion reversal. Cell-based therapies have shown encouraging results in both animal studies and a few human case reports. We designed a pilot study to assess the feasibility and safety of osteoarthritis treatment with mesenchymal stromal cells (MSCs) in humans and to obtain early efficacy information for this treatment. [Methods]: Twelve patients with chronic knee pain unresponsive to conservative treatments and radiologic evidence of osteoarthritis were treated with autologous expanded bone marrow MSCs by intra-articular injection (40×106 cells). Clinical outcomes were followed for 1 year and included evaluations of pain, disability, and quality of life. Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping. [Results]: Feasibility and safety were confirmed, and strong indications of clinical efficacy were identified. Patients exhibited rapid and progressive improvement of algofunctional indices that approached 65% to 78% by 1 year. This outcome compares favorably with the results of conventional treatments. Additionally, quantification of cartilage quality by T2 relaxation measurements demonstrated a highly significant decrease of poor cartilage areas (on average, 27%), with improvement of cartilage quality in 11 of the 12 patients. [Conclusions]: MSC therapy may be a valid alternative treatment for chronic knee osteoarthritis. The intervention is simple, does not require hospitalization or surgery, provides pain relief, and significantly improves cartilage quality.

Producción Científica, Surgical treatment options for medial compartment osteoarthritis of the knee include high tibial osteotomy, total knee arthroplasty or unicompartmental knee arthroplasty (UKA), depending on the patient's age, level of physical activity and the degree of deformity. METHODS:In this study, we evaluated the long-term results of patients who underwent the Oxford cemented meniscal-bearing unicondylar knee prosthesis through a minimally invasive approach including a clinical, functional and radiographic assessment. RESULTS:Favourable clinical and radiological outcomes were registered overall at ten years after surgery. Overall results of UKA according to the American Knee Society (AKS) using Insall's criteria showed an excellent or good outcome for 492 knees (96.28 %), fair for 11 (2.15 %) and poor for eight (1.57 %) in the post-operative long term. CONCLUSIONS:We believe that with appropriate surgical technique, patient selection, prosthetic design and specific training, surgeons should achieve good outcomes with the added advantages of a minimally invasive approach. High volume for this technique is important in our opinion