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      Concise Review: Stem/Progenitor Cell Proteoglycans Decorated with 7‐D‐4, 4‐C‐3, and 3‐B‐3(‐) Chondroitin Sulfate Motifs Are Morphogenetic Markers of Tissue Development

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          Abstract

          This study reviewed the occurrence of chondroitin sulfate (CS) motifs 4‐C‐3, 7‐D‐4, and 3‐B‐3(‐), which are expressed by progenitor cells in tissues undergoing morphogenesis. These motifs have a transient early expression pattern during tissue development and also appear in mature tissues during pathological remodeling and attempted repair processes by activated adult stem cells. The CS motifs are information and recognition modules, which may regulate cellular behavior and delineate stem cell niches in developmental tissues. One of the difficulties in determining the precise role of stem cells in tissue development and repair processes is their short engraftment period and the lack of specific markers, which differentiate the activated stem cell lineages from the resident cells. The CS sulfation motifs 7‐D‐4, 4‐C‐3, and 3‐B‐3 (‐) decorate cell surface proteoglycans on activated stem/progenitor cells and appear to identify these cells in transitional areas of tissue development and in tissue repair and may be applicable to determining a more precise role for stem cells in tissue morphogenesis. stem cells 2018;36:1475–1486

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          Convergence of Wnt, beta-catenin, and cadherin pathways.

          W Nelson (2004)
          The specification and proper arrangements of new cell types during tissue differentiation require the coordinated regulation of gene expression and precise interactions between neighboring cells. Of the many growth factors involved in these events, Wnts are particularly interesting regulators, because a key component of their signaling pathway, beta-catenin, also functions as a component of the cadherin complex, which controls cell-cell adhesion and influences cell migration. Here, we assemble evidence of possible interrelations between Wnt and other growth factor signaling, beta-catenin functions, and cadherin-mediated adhesion.
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            The surface of articular cartilage contains a progenitor cell population.

            It is becoming increasingly apparent that articular cartilage growth is achieved by apposition from the articular surface. For such a mechanism to occur, a population of stem/progenitor cells must reside within the articular cartilage to provide transit amplifying progeny for growth. Here, we report on the isolation of an articular cartilage progenitor cell from the surface zone of articular cartilage using differential adhesion to fibronectin. This population of cells exhibits high affinity for fibronectin, possesses a high colony-forming efficiency and expresses the cell fate selector gene Notch 1. Inhibition of Notch signalling abolishes colony forming ability whilst activated Notch rescues this inhibition. The progenitor population also exhibits phenotypic plasticity in its differentiation pathway in an embryonic chick tracking system, such that chondroprogenitors can engraft into a variety of connective tissue types including bone, tendon and perimysium. The identification of a chondrocyte subpopulation with progenitor-like characteristics will allow for advances in our understanding of both cartilage growth and maintenance as well as provide novel solutions to articular cartilage repair.
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              Mesenchymal Stem Cells in Tissue Repair

              The advent of mesenchymal stem cell (MSC)-based therapies for clinical therapeutics has been an exciting and new innovation for the treatment of a variety of diseases associated with inflammation, tissue damage, and subsequent regeneration and repair. Application-based ability to measure MSC potency and fate of the cells post-MSC therapy are the variables that confound the use of MSCs therapeutics in human diseases. An evaluation of MSC function and applications with attention to detail in the preparation as well as quality control and quality assurance are only as good as the assays that are developed. In vivo measures of efficacy and potency require an appreciation of the overall pathophysiology of the model and standardization of outcome measures. The new concepts of how MSC’s participate in the tissue regeneration and wound repair process and further, how this is impacted by estimates of efficacy and potency are important new topics. In this regard, this chapter will review some of the in vitro and in vivo assays for MSC function and activity and their application to the clinical arena.
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                Author and article information

                Contributors
                james.melrose@sydney.edu.au
                Journal
                Stem Cells
                Stem Cells
                10.1002/(ISSN)1549-4918
                STEM
                Stem Cells (Dayton, Ohio)
                John Wiley & Sons, Inc. (Hoboken, USA )
                1066-5099
                1549-4918
                31 July 2018
                October 2018
                : 36
                : 10 ( doiID: 10.1002/stem.v36.10 )
                : 1475-1486
                Affiliations
                [ 1 ] Bioimaging Research Hub, Cardiff School of Biosciences Cardiff University Cardiff Wales, United Kingdom
                [ 2 ] Raymond Purves Bone and Joint Research Laboratories Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney St. Leonards New South Wales Australia
                [ 3 ] School of Biosciences Cardiff University Cardiff Wales, United Kingdom
                [ 4 ] Graduate School of Biomedical Engineering University of New South Wales Sydney New South Wales Australia
                Author notes
                [*] [* ]Correspondence: Dr. J. Melrose, Raymond Purves Bone and Joint Research Laboratories, Level 10, Kolling Institute of Medical Research B6, The Royal North Shore Hospital, St. Leonards, New South Wale 2065, Australia. Telephone: +61 2 9926‐4806; Fax: +61 2 9926‐5266; e‐mail: james.melrose@ 123456sydney.edu.au
                Author information
                http://orcid.org/0000-0001-9237-0524
                Article
                STEM2860
                10.1002/stem.2860
                6381390
                29893019
                ee810845-87a5-4c79-ae1c-1e5162ff2c10
                © 2018 The Authors stem cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press

                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
                : 13 March 2018
                : 02 May 2018
                : 11 May 2018
                Page count
                Figures: 6, Tables: 0, Pages: 12, Words: 9391
                Funding
                Funded by: Arthritis Research UK
                Award ID: #19858
                Funded by: National Health and Medical Research Council Australia
                Award ID: 512167
                Categories
                Regenerative Medicine
                Regenerative Medicine
                Custom metadata
                2.0
                stem2860
                October 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.5.9 mode:remove_FC converted:20.02.2019

                Molecular medicine
                cell surface markers,chondroitin sulfate,developmental biology,differentiation,fetal stem cells,glycosaminoglycan,mesenchymal stem cells

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