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      Nomenclature clarification: synovial fibroblasts and synovial mesenchymal stem cells

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          Abstract

          Synovial-derived cells, found in the synovial membrane of human joints, were obtained by digestion of the synovial membrane and were subsequently expanded in vitro. The identity of synovial-derived cells has long been a topic of debate. The terms “type B synoviocytes,” “fibroblast-like synoviocytes (FLS),” “synovium-derived mesenchymal stem cells (MSCs),” and “synovial fibroblasts (SF)” appeared in different articles related to human synovial-derived cells in various disease models, yet they seemed to be describing the same cell type. However, to date, there is no clear standard to distinguish these terms; thus, the hypothesis that they represent the same cell type is currently inconclusive. Therefore, this review aims to clarify the similarities and differences between these terms and to diffuse the chaotic nomenclature of synovial-derived cells.

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          Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells.

          Katarina Le Blanc, Ida Rasmusson, Berit Sundberg … (2004)
          Adult bone-marrow-derived mesenchymal stem cells are immunosuppressive and prolong the rejection of mismatched skin grafts in animals. We transplanted haploidentical mesenchymal stem cells in a patient with severe treatment-resistant grade IV acute graft-versus-host disease of the gut and liver. Clinical response was striking. The patient is now well after 1 year. We postulate that mesenchymal stem cells have a potent immunosuppressive effect in vivo.
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            Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis.

            Joanna Stanczyk, Deena Pedrioli, Fabia Brentano … (2008)
            MicroRNAs (miRNA) have recently emerged as a new class of modulators of gene expression. In this study we investigated the expression, regulation, and function of miR-155 and miR-146a in rheumatoid arthritis (RA) synovial fibroblasts (RASFs) and RA synovial tissue. Locked nucleic acid microarray was used to screen for differentially expressed miRNA in RASFs treated with tumor necrosis factor alpha (TNFalpha). TaqMan-based real-time polymerase chain reaction was applied to measure the levels of miR-155 and miR-146a. Enforced overexpression of miR-155 was used to investigate the function of miR-155 in RASFs. Microarray analysis of miRNA expressed in RASFs treated with TNFalpha revealed a prominent up-regulation of miR-155. Constitutive expression of both miR-155 and miR-146a was higher in RASFs than in those from patients with osteoarthritis (OA), and expression of miR-155 could be further induced by TNFalpha, interleukin-1beta, lipopolysaccharide, poly(I-C), and bacterial lipoprotein. The expression of miR-155 in RA synovial tissue was higher than in OA synovial tissue. Enforced expression of miR-155 in RASFs was found to repress the levels of matrix metalloproteinase 3 (MMP-3) and reduce the induction of MMPs 3 and 1 by Toll-like receptor ligands and cytokines. Moreover, compared with monocytes from RA peripheral blood, RA synovial fluid monocytes displayed higher levels of miR-155. This study provides the first description of increased expression of miRNA miR-155 and miR-146a in RA. Based on these findings, we postulate that the inflammatory milieu may alter miRNA expression profiles in resident cells of the rheumatoid joints. Considering the repressive effect of miR-155 on the expression of MMPs 3 and 1 in RASFs, we hypothesize that miR-155 may be involved in modulation of the destructive properties of RASFs.
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              Fibroblast-like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis

              Marta F. Bustamante, Ricard Garcia-Carbonell, Katrijn Whisenant … (2017)
              An increasing number of studies show how changes in intracellular metabolic pathways alter tumor and immune cell function. However, little information about metabolic changes in other cell types, including synovial fibroblasts, is available. In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are the most common cell type at the pannus–cartilage junction and contribute to joint destruction through their production of cytokines, chemokines, and matrix-degrading molecules and by migrating and invading joint cartilage. In this review, we show that these cells differ from healthy synovial fibroblasts, not only in their marker expression, proto-oncogene expression, or their epigenetic changes, but also in their intracellular metabolism. These metabolic changes must occur due to the stressful microenvironment of inflamed tissues, where concentrations of crucial nutrients such as glucose, glutamine, and oxygen are spatially and temporally heterogeneous. In addition, these metabolic changes will increase metabolite exchange between fibroblast and other synovial cells, which can potentially be activated. Glucose and phospholipid metabolism as well as bioactive lipids, including sphingosine-1-phosphate and lysophosphatidic acid, among others, are involved in FLS activation. These metabolic changes likely contribute to FLS involvement in aspects of immune response initiation or abnormal immune responses and strongly contribute to joint destruction.
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                Author and article information

                Contributors
                Fangqi Li: lifq6@mail2.sysu.edu.cn
                Yiyong Tang: tangyiy@mail2.sysu.edu.cn
                Bin Song: songbin3@mail.sysu.edu.cn
                Menglei Yu: yumenglei@mail.sysu.edu.cn
                Qingyue Li: liqy37@mail2.sysu.edu.cn
                Congda Zhang: zhangcd@mail2.sysu.edu.cn
                Jingyi Hou:
                ORCID: http://orcid.org/0000-0001-7457-5163
                houjy7@mail.sysu.edu.cn
                Rui Yang: yangr@mail.sysu.edu.cn
                Journal
                Journal ID (nlm-ta): Stem Cell Res Ther
                Journal ID (iso-abbrev): Stem Cell Res Ther
                Title: Stem Cell Research & Therapy
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1757-6512
                Publication date (Electronic): 19 August 2019
                Publication date PMC-release: 19 August 2019
                Publication date Collection: 2019
                Volume: 10
                Electronic Location Identifier: 260
                Affiliations
                ISNI 0000 0004 1791 7851, GRID grid.412536.7, Department of Orthopedic, , Sun Yat-sen Memorial Hospital Sun Yat-sen University, ; NO.107 Yan Jiang West Road, Guangzhou, Guangdong Province, 510120 China
                Author information
                http://orcid.org/0000-0001-7457-5163
                Article
                Publisher ID: 1359
                DOI: 10.1186/s13287-019-1359-x
                PMC ID: 6701095
                PubMed ID: 31426847
                SO-VID: f77c7f0c-1582-43fe-b267-2efcbd815fbc
                Copyright © © The Author(s). 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.

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                Subject: Review
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                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Molecular medicine
                Keywords: synovium,synoviocytes,fibroblasts,mesenchymal stem cells,mscs
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: synovium, synoviocytes, fibroblasts, mesenchymal stem cells, mscs

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