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      Mesenchymal stem cell-derived extracellular vesicles, osteoimmunology and orthopedic diseases

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          Abstract

          Mesenchymal stem cells (MSCs) play an important role in tissue healing and regenerative medicine due to their self-renewal and multi-directional differentiation properties. MSCs exert their therapeutic effects mainly via the paracrine pathway, which involves the secretion of extracellular vesicles (EVs). EVs have a high drug loading capacity and can transport various molecules, such as proteins, nucleic acids, and lipids, that can modify the course of diverse diseases. Due to their ability to maintain the therapeutic effects of their parent cells, MSC-derived EVs have emerged as a promising, safe cell-free treatment approach for tissue regeneration. With advances in inflammation research and emergence of the field of osteoimmunology, evidence has accumulated pointing to the role of inflammatory and osteoimmunological processes in the occurrence and progression of orthopedic diseases. Several studies have shown that MSC-derived EVs participate in bone regeneration and the pathophysiology of orthopedic diseases by regulating the inflammatory environment, enhancing angiogenesis, and promoting the differentiation and proliferation of osteoblasts and osteoclasts. In this review, we summarize recent advances in the application and functions of MSC-derived EVs as potential therapies against orthopedic diseases, including osteoarthritis, intervertebral disc degeneration, osteoporosis and osteonecrosis.

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          Multilineage potential of adult human mesenchymal stem cells.

          Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.
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            Extracellular vesicles: biology and emerging therapeutic opportunities.

            Within the past decade, extracellular vesicles have emerged as important mediators of intercellular communication, being involved in the transmission of biological signals between cells in both prokaryotes and higher eukaryotes to regulate a diverse range of biological processes. In addition, pathophysiological roles for extracellular vesicles are beginning to be recognized in diseases including cancer, infectious diseases and neurodegenerative disorders, highlighting potential novel targets for therapeutic intervention. Moreover, both unmodified and engineered extracellular vesicles are likely to have applications in macromolecular drug delivery. Here, we review recent progress in understanding extracellular vesicle biology and the role of extracellular vesicles in disease, discuss emerging therapeutic opportunities and consider the associated challenges.
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              Current knowledge on exosome biogenesis and release

              Exosomes are nanosized membrane vesicles released by fusion of an organelle of the endocytic pathway, the multivesicular body, with the plasma membrane. This process was discovered more than 30 years ago, and during these years, exosomes have gone from being considered as cellular waste disposal to mediate a novel mechanism of cell-to-cell communication. The exponential interest in exosomes experienced during recent years is due to their important roles in health and disease and to their potential clinical application in therapy and diagnosis. However, important aspects of the biology of exosomes remain unknown. To explore the use of exosomes in the clinic, it is essential that the basic molecular mechanisms behind the transport and function of these vesicles are better understood. We have here summarized what is presently known about how exosomes are formed and released by cells. Moreover, other cellular processes related to exosome biogenesis and release, such as autophagy and lysosomal exocytosis are presented. Finally, methodological aspects related to exosome release studies are discussed.
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                Author and article information

                Contributors
                Journal
                PeerJ
                PeerJ
                peerj
                PeerJ
                PeerJ Inc. (San Diego, USA )
                2167-8359
                24 January 2023
                2023
                : 11
                : e14677
                Affiliations
                [1 ]Department of Orthopedics, Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province , Luoyang, Henan, China
                [2 ]Department of Orthopedics, Luoyang Central Hospital Affiliated to Zhengzhou University , Luoyang, Henan, China
                Article
                14677
                10.7717/peerj.14677
                9881470
                36710868
                58ea412e-d6d5-4036-82cf-6a33d6d4cf3c
                ©2023 Ma et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                : 29 August 2022
                : 12 December 2022
                Funding
                Funded by: The National Natural Science Foundation of China
                Award ID: 82004396
                Award ID: 82074472
                Funded by: The Project of Science and Technology of Henan Province
                Award ID: 212102311089
                Funded by: The Heluo youth talent promotion project
                Award ID: 2022HLTJ15
                This work is supported in China by the National Natural Science Foundation of China (82004396, 82074472); the Project of Science and Technology of Henan Province (212102311089); and the Heluo youth talent promotion project (2022HLTJ15). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Bioengineering
                Cell Biology
                Immunology
                Orthopedics

                mesenchymal stem cell,extracellular vesicles,osteoimmunology,orthopedic diseases

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