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      Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis

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          Abstract

          Osteoporosis is a systemic metabolic bone disease with characteristics of bone loss and microstructural degeneration. The personal and societal costs of osteoporosis are increasing year by year as the ageing of population, posing challenges to public health care. Homing disorders, impaired capability of osteogenic differentiation, senescence of mesenchymal stem cells (MSCs), an imbalanced microenvironment, and disordered immunoregulation play important roles during the pathogenesis of osteoporosis. The MSC transplantation promises to increase osteoblast differentiation and block osteoclast activation, and to rebalance bone formation and resorption. Preclinical investigations on MSC transplantation in the osteoporosis treatment provide evidences of enhancing osteogenic differentiation, increasing bone mineral density, and halting the deterioration of osteoporosis. Meanwhile, the latest techniques, such as gene modification, targeted modification and co‐transplantation, are promising approaches to enhance the therapeutic effect and efficacy of MSCs. In addition, clinical trials of MSC therapy to treat osteoporosis are underway, which will fill the gap of clinical data. Although MSCs tend to be effective to treat osteoporosis, the urgent issues of safety, transplant efficiency and standardization of the manufacturing process have to be settled. Moreover, a comprehensive evaluation of clinical trials, including safety and efficacy, is still needed as an important basis for clinical translation.

          Abstract

          Osteoporosis occurs when the orchestrated balance between bone formation by osteoblasts and bone destruction by osteoclasts breaks down, and this process is closely associated with MSCs. Existing preclinical evidences of MSCs derived from different tissues support MSCs‐based cell therapy as a possible radical approach to the prevention and treatment of osteoporosis. Clinical trials of MSC transplantation for osteoporosis mainly focus on the application of autologous cells and will fill the gap of clinical data.

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          Communication by Extracellular Vesicles: Where We Are and Where We Need to Go.

          In multicellular organisms, distant cells can exchange information by sending out signals composed of single molecules or, as increasingly exemplified in the literature, via complex packets stuffed with a selection of proteins, lipids, and nucleic acids, called extracellular vesicles (EVs; also known as exosomes and microvesicles, among other names). This Review covers some of the most striking functions described for EV secretion but also presents the limitations on our knowledge of their physiological roles. While there are initial indications that EV-mediated pathways operate in vivo, the actual nature of the EVs involved in these effects still needs to be clarified. Here, we focus on the context of tumor cells and their microenvironment, but similar results and challenges apply to all patho/physiological systems in which EV-mediated communication is proposed to take place.
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            Taking dendritic cells into medicine.

            Dendritic cells (DCs) orchestrate a repertoire of immune responses that bring about resistance to infection and silencing or tolerance to self. In the settings of infection and cancer, microbes and tumours can exploit DCs to evade immunity, but DCs also can generate resistance, a capacity that is readily enhanced with DC-targeted vaccines. During allergy, autoimmunity and transplant rejection, DCs instigate unwanted responses that cause disease, but, again, DCs can be harnessed to silence these conditions with novel therapies. Here we present some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy.
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              Bone regeneration: current concepts and future directions

              Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis.
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                Author and article information

                Contributors
                lvlw@bjmu.edu.cn , kqzhouysh@hsc.pku.edu.cn
                kqzhouysh@hsc.pku.edu.cn
                Journal
                Cell Prolif
                Cell Prolif
                10.1111/(ISSN)1365-2184
                CPR
                Cell Proliferation
                John Wiley and Sons Inc. (Hoboken )
                0960-7722
                1365-2184
                18 November 2020
                January 2021
                : 54
                : 1 ( doiID: 10.1111/cpr.v54.1 )
                : e12956
                Affiliations
                [ 1 ] Department of Prosthodontics Peking University School and Hospital of Stomatology National Engineering Laboratory for Digital and Material Technology of Stomatology National Clinical Research Center for Oral Disease Beijing Key Laboratory of Digital Stomatology Beijing P.R. China
                Author notes
                [*] [* ] Correspondence

                Longwei Lv and Yongsheng Zhou, Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, P.R. China.

                Email: lvlw@ 123456bjmu.edu.cn (L. L.) kqzhouysh@ 123456hsc.pku.edu.cn (Y. Z.)

                Author information
                https://orcid.org/0000-0002-2912-1530
                https://orcid.org/0000-0002-4332-0878
                Article
                CPR12956
                10.1111/cpr.12956
                7791182
                33210341
                1b0056ee-5b3a-43a0-bf69-f73cc49b9f8b
                © 2020 The Authors. Cell Proliferation published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 July 2020
                : 21 October 2020
                : 23 October 2020
                Page count
                Figures: 4, Tables: 3, Pages: 19, Words: 13913
                Funding
                Funded by: Natural Science Foundation of Beijing Municipality , open-funder-registry 10.13039/501100004826;
                Award ID: 7192228
                Award ID: L182006
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                January 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.6 mode:remove_FC converted:08.01.2021

                Cell biology
                clinical trial,mesenchymal stem cells,osteoporosis,preclinical investigation,stem cell therapy

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