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Cell therapy is becoming established in many fields, including oncology with CAR-Ts or in regenerative medicine for cardiovascular diseases, diabetes or musculoskeletal disorders with mesenchymal stromal cells. These therapeutic cells are called advanced therapy medicinal products (ATMPs) and include all processes including cells manipulated to obtain reprogramming (iPS), to induce gene expression or by genome editing to modify the expression of a gene. The development of new biomaterial supports that can be 3D printed and take the desired shape of the target tissue before being colonised by the cellular elements necessary for their biological functions and replace the failing organ. All of these new technologies are driving innovation and the development of tomorrow’s bio-medicines. These new biotherapies will profoundly modify patient care in all areas, changing medical practices but with a considerable societal impact. Thus, the development and clinical research on cellular biotherapies are essential health issues but with a major ethical, societal and economic impact.

Mesenchymal stromal or stem cells (MSCs) are multipotent adult cells that can be isolated from a variety of adult or neonatal tissues, such as bone marrow, fat tissue, placenta or umbilical cord. A therapy based on MSCs can be justified in osteoarthritis (OA) thanks to their differentiation abilities but mostly, to their paracrine and immunosuppressive properties. Possible therapeutic strategies therefore rely on the articular injection of MSCs suspensions for trophic activity or the implantation of MSCs combined with biodegradable materials for tissue engineering applications. Depending on the mode of administration and behavior after implantation, they can decrease local inflammation, prevent chondrocyte hypertrophy and apoptosis as well as differentiate into cartilage-forming chondrocytes. In this review, we summarize pathophysiological and mechanistic data and discuss perspectives confirming the interest of MSCs as a potential therapeutic strategy in OA., (© 2018 médecine/sciences – Inserm.)

Our societies are facing with the emergence of an exponential number of patients with age-related degenerative chronic diseases such as osteoarthritis or osteoporosis. The "better" aging will thus be at the center of the next medical challenges in order to delay the loss of independence of the elderly and reduce costs of our health services. Over the last 5 years, based on innovative mouse models or in vitro studies, several research teams have demonstrated that many age-related degenerative diseases have in common a deleterious accumulation of so-called senescent cells in their respective deficient tissues. Thus, under the concept of senolysis, it has been proposed to target pharmacologically in vivo these cells to eliminate them and thus delay the emergence of these chronic diseases of the elderly subject. We propose here to summarize the recent strategies applied for the identification of novel senolytics and their uses in osteoarthritis and osteoporosis therapies., (© 2018 médecine/sciences – Inserm.)

Mesenchymal stem cells/multipotent marrow stromal cells (MSC) have the ability to participate in there construction of tissues both directly by providing repair cells (essentially those originating from mesoderm)and indirectly by modulating inflammatory and immune responses. This wide range of properties makes these cells very appealing to treat various pathological conditions. They have been first used in 1995 as supportive cells to facilitate hematopoietic stem cells engraftment, and then to minimize the deleterious consequences of graft versus host disease by their immunosuppressive function. Their robust osteogenic differentiation capacity has also been evaluated in numerous preclinical settings of healing/repair but more rarely in human clinical trials. During the past 10-15 years, the potential benefit of their paracrine actions has been tested in various situations such as to facilitate repair after cutaneous defects after burns or lower consequences of ischemic strokes. The purpose of this series of short texts is not to give an exhaustive panorama, but to discuss some well-identified indications in four different fields : auto-immune diseases,bone repair, vascular regeneration and eye lesions such as corneal and retinal defects.

Purpose: Extracorporal shock wave therapy has recently been proposed with good results (70%) for treatment of persistent painful calcifying tendinitis of the shoulder. The aim of this study was to evaluate the early impact of shock wave therapy on the anatomic structures of the shoulder., Materials and Methods: Eight patients (7 women and 1 man, with mean age of 48 years) were prospectively followed up after undergoing shock wave therapy (1500 pulses with 0.28 mJ/mm2 energy). MRI (T1: 500/12 [TR/TE] and STIR: 7200/60/180/180 [TR/TE/TI/alpha]) were obtained 2 hours before and 15 days after the procedure; in addition for 5 of them one more examination was carried out 6 hours after extracorporal shock wave therapy., Results: There was no significant signal change of the humeral bone or rotator cuff, and the calcification size, when seen (6 times), was unchanged at successive MR examinations. One patient had subcutaneous fat signal change (STIR) next to the zone of impact, which resolved 15 days after the extracorporal shock wave therapy. No bursitis or joint effusion was found., Conclusion: Shock wave therapy has no early complications or significant impact on the anatomic structures of the shoulder.

Purpose: Interleukin -1 receptor antagonist ( IL-1Ra ) is a new option among biotherapies against rheumatoid arthritis ( RA )., The Aim: of this review is to recall the rationale of use of IL-1Ra and to analyse the results available in the current literature., Current Knowledge and Key Points: Pathophysiological data of RA give a specific position for IL-1 as a potential target for immunotherapy in this disease, confirmed in animal models. Phase II and III studies with IL-1Ra (Anakinra) demonstrated clinical efficacy versus placebo (42% responders in ACR 20 in Anakinra + methotrexate, and 23% in the placebo + methotrexate group at 24 weeks) and a structural effect (slowing of radiological progression at six months). Anakinra has obtained an European license and is indicated in RA not controlled by methotrexate, in daily subcutaneous administration (100 mg/day), in combination with methotrexate. Tolerance is fair; the most frequent side effect is represented by injection site reactions., Future Prospects and Projects: This ambulatory biotherapy offers new perspectives in combination with other slow acting drugs as well as biologic agents such as anti-TNF, currently under evaluation.

Introduction: Tumor necrosis factor (TNF) blocking agents have changed the therapeutic approach in rheumatoid arthritis, but a true clinical remission remains rare. Gene therapy opens new perspectives in immunotherapy in rheumatoid arthritis. This review focuses on the research, data and clinical development in rheumatoid arthritis using this strategy., Current Knowledge and Key Points: New therapeutical targets have been described besides the cytokine inhibitors: apoptosis inducers, angiogenesis inhibitors and metalloprotease inhibitors, cell activation and signalization have been used in experimental models to inhibit arthritis. Gene therapy makes it possible to better understand the physiopathology of rheumatoid arthritis and offers the opportunity to induce true remissions of experimental arthritis., Future Prospects and Projects: Biotechnology allows the development of new safer vectors which permit long-term expression. However, the difficulties to produce high titers and safe vectors limit the use of this strategy. The previous clinical data on gene therapy in rheumatoid arthritis are limited to feasibility studies. We believe that the efficiency of gene therapy will be obtained by combining two or more complementary targets.

One hundred and ninety one patients with rheumatoid arthritis were included in an open prospective trial with the aim of evaluating the acceptability, efficacy and therapeutic maintenance levels of methotrexate. The mean treatment duration was 19 +/- 13.2 (3-58) months and the mean weekly dose of methotrexate 10.2 +/- 0.2 mg. Analysis of the 191 patients by intention to treat showed a statistically significant improvement in all clinical parameters as well as a significant fall in sedimentation rate with a corticosteroid-sparing effect. The therapeutic maintenance level of methotrexate was 73% at one year, 65% at 2 years and 46% at 5 years. Adverse reactions occurred in 71 patients (37.1%) including 30 who stopped methotrexate permanently as a result. With cautious and strict patient selection, methotrexate could be used in RA as basic treatment of first choice.

The wrist is involved, often as the initial lesion, in 85% of patients with rheumatoid arthritis. . An early diagnosis results in a better management. At an advanced stage the functional disablement may be severe; it can be due to instability of the wrist, sometimes associated with palmar dislocation of the carpus, to rupture of tendons facilitated by dorsal dislocation of the ulnar head, and to the limited mobility of the wrist, notably in supination. Treatment is part of the overall management of rheumatoid arthritis, with surgery playing a major role.