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      Immunomodulatory effects of mesenchymal stem cells in peripheral nerve injury

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          Abstract

          Various immune cells and cytokines are present in the aftermath of peripheral nerve injuries (PNI), and coordination of the local inflammatory response is of great significance for the recovery of PNI. Mesenchymal stem cells (MSCs) exhibit immunosuppressive and anti-inflammatory abilities which can accelerate tissue regeneration and attenuate inflammation, but the role of MSCs in the regulation of the local inflammatory microenvironment after PNI has not been widely studied. Here, we summarize the known interactions between MSCs, immune cells, and inflammatory cytokines following PNI with a focus on the immunosuppressive role of MSCs. We also discuss the immunomodulatory potential of MSC-derived extracellular vesicles as a new cell-free treatment for PNI.

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          Most cited references138

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          Exploring the full spectrum of macrophage activation.

          Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.
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            Macrophages in Tissue Repair, Regeneration, and Fibrosis.

            Inflammatory monocytes and tissue-resident macrophages are key regulators of tissue repair, regeneration, and fibrosis. After tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play critical roles during the initiation, maintenance, and resolution phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, such that uncontrolled production of inflammatory mediators and growth factors, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contribute to a state of persistent injury, and this could lead to the development of pathological fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound-healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue-regenerating phenotypes after injury, and we highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically.
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              Macrophage plasticity and polarization in tissue repair and remodelling.

              Mononuclear phagocyte plasticity includes the expression of functions related to the resolution of inflammation, tissue repair and remodelling, particularly when these cells are set in an M2 or an M2-like activation mode. Macrophages are credited with an essential role in remodelling during ontogenesis. In extraembryonic life, under homeostatic conditions, the macrophage trophic and remodelling functions are recapitulated in tissues such as bone, mammary gland, decidua and placenta. In pathology, macrophages are key components of tissue repair and remodelling that occur during wound healing, allergy, parasite infection and cancer. Interaction with cells bearing stem or progenitor cell properties is likely an important component of the role of macrophages in repair and remodelling. These properties of cells of the monocyte-macrophage lineage may represent a tool and a target for therapeutic exploitation. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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                Author and article information

                Contributors
                wangyi1@301hospital.com.cn
                pengjiang301@126.com
                drtang304@126.com
                Journal
                Stem Cell Res Ther
                Stem Cell Res Ther
                Stem Cell Research & Therapy
                BioMed Central (London )
                1757-6512
                15 January 2022
                15 January 2022
                2022
                : 13
                : 18
                Affiliations
                [1 ]GRID grid.414252.4, ISNI 0000 0004 1761 8894, The Fourth Medical Center of Chinese PLA General Hospital, ; Beijing, 100853 People’s Republic of China
                [2 ]GRID grid.414252.4, ISNI 0000 0004 1761 8894, Institute of Orthopedics, , Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, ; Beijing, 100853 People’s Republic of China
                [3 ]GRID grid.414252.4, ISNI 0000 0004 1761 8894, Department of Stomatology, First Medical Center, , Chinese PLA General Hospital, ; Beijing, 100853 People’s Republic of China
                [4 ]GRID grid.454145.5, ISNI 0000 0000 9860 0426, The School of Medicine, , Jinzhou Medical University, ; Jinzhou, 121099 People’s Republic of China
                [5 ]GRID grid.411634.5, ISNI 0000 0004 0632 4559, Department of Spine Surgery, , Peking University People’s Hospital, ; Beijing, 100044 People’s Republic of China
                [6 ]GRID grid.216938.7, ISNI 0000 0000 9878 7032, The School of Medicine, , Nankai University, ; Tianjin, 300071 People’s Republic of China
                Article
                2690
                10.1186/s13287-021-02690-2
                8760713
                35033187
                b4eb723a-0927-46c0-8805-78285b8755ab
                © The Author(s) 2022

                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
                : 22 October 2021
                : 18 December 2021
                Funding
                Funded by: Medical Research and Development Projects
                Award ID: AWS17J005
                Award ID: AWS17J005
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                Molecular medicine
                mesenchymal stem cells (mscs),immunomodulation,peripheral nerve injury,review

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