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      Emerging role of mesenchymal stem/stromal cells (MSCs) and MSCs-derived exosomes in bone- and joint-associated musculoskeletal disorders: a new frontier

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          Abstract

          Exosomes are membranous vesicles with a 30 to 150 nm diameter secreted by mesenchymal stem/stromal cells (MSCs) and other cells, such as immune cells and cancer cells. Exosomes convey proteins, bioactive lipids, and genetic components to recipient cells, such as microRNAs (miRNAs). Consequently, they have been implicated in regulating intercellular communication mediators under physiological and pathological circumstances. Exosomes therapy as a cell-free approach bypasses many concerns regarding the therapeutic application of stem/stromal cells, including undesirable proliferation, heterogeneity, and immunogenic effects. Indeed, exosomes have become a promising strategy to treat human diseases, particularly bone- and joint-associated musculoskeletal disorders, because of their characteristics, such as potentiated stability in circulation, biocompatibility, low immunogenicity, and toxicity. In this light, a diversity of studies have indicated that inhibiting inflammation, inducing angiogenesis, provoking osteoblast and chondrocyte proliferation and migration, and negative regulation of matrix-degrading enzymes result in bone and cartilage recovery upon administration of MSCs-derived exosomes. Notwithstanding, insufficient quantity of isolated exosomes, lack of reliable potency test, and exosomes heterogeneity hurdle their application in clinics. Herein, we will deliver an outline respecting the advantages of MSCs-derived exosomes-based therapy in common bone- and joint-associated musculoskeletal disorders. Moreover, we will have a glimpse the underlying mechanism behind the MSCs-elicited therapeutic merits in these conditions.

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          Most cited references217

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          Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis

          The use of extracellular vesicles, specifically exosomes, as carriers of biomarkers in extracellular spaces has been well demonstrated. Despite their promising potential, the use of exosomes in the clinical setting is restricted due to the lack of standardization in exosome isolation and analysis methods. The purpose of this review is to not only introduce the different types of extracellular vesicles but also to summarize their differences and similarities, and discuss different methods of exosome isolation and analysis currently used. A thorough understanding of the isolation and analysis methods currently being used could lead to some standardization in the field of exosomal research, allowing the use of exosomes in the clinical setting to become a reality.
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            Isolation and characterization of exosomes from cell culture supernatants and biological fluids.

            Exosomes are small membrane vesicles found in cell culture supernatants and in different biological fluids. Exosomes form in a particular population of endosomes, called multivesicular bodies (MVBs), by inward budding into the lumen of the compartment. Upon fusion of MVBs with the plasma membrane, these internal vesicles are secreted. Exosomes possess a defined set of membrane and cytosolic proteins. The physiological function of exosomes is still a matter of debate, but increasing results in various experimental systems suggest their involvement in multiple biological processes. Because both cell-culture supernatants and biological fluids contain different types of lipid membranes, it is critical to perform high-quality exosome purification. This unit describes different approaches for exosome purification from various sources, and discusses methods to evaluate the purity and homogeneity of the purified exosome preparations.
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              Osteoporosis: now and the future.

              Osteoporosis is a common disease characterised by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. With an ageing population, the medical and socioeconomic effect of osteoporosis, particularly postmenopausal osteoporosis, will increase further. A detailed knowledge of bone biology with molecular insights into the communication between bone-forming osteoblasts and bone-resorbing osteoclasts and the orchestrating signalling network has led to the identification of novel therapeutic targets. Novel treatment strategies have been developed that aim to inhibit excessive bone resorption and increase bone formation. The most promising novel treatments include: denosumab, a monoclonal antibody for receptor activator of NF-κB ligand, a key osteoclast cytokine; odanacatib, a specific inhibitor of the osteoclast protease cathepsin K; and antibodies against the proteins sclerostin and dickkopf-1, two endogenous inhibitors of bone formation. This overview discusses these novel therapies and explains their underlying physiology. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                dr.hadi.gerami@gmail.com
                roya.khorram.md@gmail.com
                Soheil.rasoolzadegann@gmail.com
                Saeidmardpour@gmail.com
                Poorianak@gmail.com
                srnhoshyar2@gmail.com
                almustaqbalstaff123@gmail.com
                amir.aminian1975@gmail.com , amir_aminian@yahoo.com
                Shrsamimi@gmail.com
                Journal
                Eur J Med Res
                Eur J Med Res
                European Journal of Medical Research
                BioMed Central (London )
                0949-2321
                2047-783X
                20 February 2023
                20 February 2023
                2023
                : 28
                : 86
                Affiliations
                [1 ]GRID grid.412571.4, ISNI 0000 0000 8819 4698, Bone and Joint Diseases Research Center, , Shiraz University of Medical Sciences, ; Shiraz, Iran
                [2 ]GRID grid.412571.4, ISNI 0000 0000 8819 4698, Bone and Joint Diseases Research Center, Department of Orthopedic Surgery, , Shiraz University of Medical Sciences, ; Shiraz, Iran
                [3 ]GRID grid.411600.2, Department of Surgery, School of Medicine, , Shahid Beheshti University of Medical Sciences, ; Tehran, Iran
                [4 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Department of Radiology, Imam Khomeini Hospital, , Tehran University of Medical Sciences, ; Tehran, Iran
                [5 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, , Tehran University of Medical Sciences, ; Tehran, Iran
                [6 ]GRID grid.411036.1, ISNI 0000 0001 1498 685X, Obstetrician, Gynaecology & Infertility Department, , Isfahan University of Medical Sciences, ; Isfahan, Iran
                [7 ]GRID grid.460855.a, Anesthesia Technology Department, , Al-Turath University College, ; Al Mansour, Baghdad, Iraq
                [8 ]GRID grid.411746.1, ISNI 0000 0004 4911 7066, Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, , Iran University of Medical Sciences, ; Tehran, Iran
                [9 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Tehran University of Medical Sciences, ; Tehran, Iran
                Article
                1034
                10.1186/s40001-023-01034-5
                9939872
                36803566
                f33ca0ff-31c5-4af2-a121-65abdac3e401
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 27 August 2022
                : 26 January 2023
                Categories
                Review
                Custom metadata
                © The Author(s) 2023

                Medicine
                mesenchymal stem/stromal cells (mscs),exosomes,musculoskeletal disorders bone,cartilage

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