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      Repair of Damaged Articular Cartilage: Current Approaches and Future Directions

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          Abstract

          Articular hyaline cartilage is extensively hydrated, but it is neither innervated nor vascularized, and its low cell density allows only extremely limited self-renewal. Most clinical and research efforts currently focus on the restoration of cartilage damaged in connection with osteoarthritis or trauma. Here, we discuss current clinical approaches for repairing cartilage, as well as research approaches which are currently developing, and those under translation into clinical practice. We also describe potential future directions in this area, including tissue engineering based on scaffolding and/or stem cells as well as a combination of gene and cell therapy. Particular focus is placed on cell-based approaches and the potential of recently characterized chondro-progenitors; progress with induced pluripotent stem cells is also discussed. In this context, we also consider the ability of different types of stem cell to restore hyaline cartilage and the importance of mimicking the environment in vivo during cell expansion and differentiation into mature chondrocytes.

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          Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial.

          Timothy McAlindon, Michael LaValley, William F Harvey … (2017)
          Synovitis is common and is associated with progression of structural characteristics of knee osteoarthritis. Intra-articular corticosteroids could reduce cartilage damage associated with synovitis but might have adverse effects on cartilage and periarticular bone.
          Article 0 comments Cited 237 times – based on 0 reviews     Review now
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            Human gingiva-derived mesenchymal stem cells elicit polarization of m2 macrophages and enhance cutaneous wound healing.

            Qun-Zhou Zhang, Wen-Ru Su, Shi-Hong Shi … (2010)
            Increasing evidence has supported the important role of mesenchymal stem cells (MSCs) in wound healing, however, the underlying mechanism remains unclear. Recently, we have isolated a unique population of MSCs from human gingiva (GMSCs) with similar stem cell-like properties, immunosuppressive, and anti-inflammatory functions as human bone marrow-derived MSCs (BMSCs). We describe here the interplay between GMSCs and macrophages and the potential relevance in skin wound healing. When cocultured with GMSCs, macrophages acquired an anti-inflammatory M2 phenotype characterized by an increased expression of mannose receptor (MR; CD206) and secretory cytokines interleukin (IL)-10 and IL-6, a suppressed production of tumor necrosis factor (TNF)-α, and decreased ability to induce Th-17 cell expansion. In vivo, we demonstrated that systemically infused GMSCs could home to the wound site in a tight spatial interaction with host macrophages, promoted them toward M2 polarization, and significantly enhanced wound repair. Mechanistically, GMSC treatment mitigated local inflammation mediated by a suppressed infiltration of inflammatory cells and production of IL-6 and TNF-α, and an increased expression of IL-10. The GMSC-induced suppression of TNF-α secretion by macrophages appears to correlate with impaired activation of NFκB p50. These findings provide first evidence that GMSCs are capable to elicit M2 polarization of macrophages, which might contribute to a marked acceleration of wound healing.
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              Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: implications for cartilage tissue repair.

              J Kisiday, M. Jin, B Kurz … (2002)
              Emerging medical technologies for effective and lasting repair of articular cartilage include delivery of cells or cell-seeded scaffolds to a defect site to initiate de novo tissue regeneration. Biocompatible scaffolds assist in providing a template for cell distribution and extracellular matrix (ECM) accumulation in a three-dimensional geometry. A major challenge in choosing an appropriate scaffold for cartilage repair is the identification of a material that can simultaneously stimulate high rates of cell division and high rates of cell synthesis of phenotypically specific ECM macromolecules until repair evolves into steady-state tissue maintenance. We have devised a self-assembling peptide hydrogel scaffold for cartilage repair and developed a method to encapsulate chondrocytes within the peptide hydrogel. During 4 weeks of culture in vitro, chondrocytes seeded within the peptide hydrogel retained their morphology and developed a cartilage-like ECM rich in proteoglycans and type II collagen, indicative of a stable chondrocyte phenotype. Time-dependent accumulation of this ECM was paralleled by increases in material stiffness, indicative of deposition of mechanically functional neo-tissue. Taken together, these results demonstrate the potential of a self-assembling peptide hydrogel as a scaffold for the synthesis and accumulation of a true cartilage-like ECM within a three-dimensional cell culture for cartilage tissue repair.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 11 August 2018
                Publication date Collection: August 2018
                Volume: 19
                Issue: 8
                Electronic Location Identifier: 2366
                Affiliations
                [1 ]Institute for Regenerative Medicine, Sechenov University, 8-2 Trubetskaya St., Moscow 119991, Russia; grebeneka@ 123456gmail.com (E.A.G.); svetlana.gornost@ 123456gmail.com (S.N.G.); telpuhov@ 123456mail.ru (V.I.T.); timashev.peter@ 123456gmail.com (P.S.T.)
                [2 ]Department of Trauma, Orthopedics and Disaster Surgery, Sechenov University, 8-2 Trubetskaya St., Moscow 119991, Russia; dr.lychagin@ 123456mail.ru
                [3 ]Department of Polymers and Composites, N. N. Semenov Institute of Chemical Physics, 4 Kosygin St., Moscow 119991, Russia
                [4 ]Institute of Photonic Technologies, Research Center “Crystallography and Photonics”, RAS, 2 Pionerskaya St., Troitsk, Moscow 142190, Russia
                [5 ]Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum 6D, Stockholm 17177, Sweden
                Author notes
                Article
                Publisher ID: ijms-19-02366
                DOI: 10.3390/ijms19082366
                PMC ID: 6122081
                PubMed ID: 30103493
                SO-VID: 670a13f4-04e9-4c1e-a7d0-138b8fe294dc
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 29 June 2018
                Date accepted : 07 August 2018
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: articular hyaline cartilage,regenerative medicine approaches,stem cells,tissue-engineered constructs,cell-based therapy,micro-fracture,mosaicplasty,autologous chondrocyte implantation (aci),matrix-induced autologous chondrocyte implantation (maci)
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: articular hyaline cartilage, regenerative medicine approaches, stem cells, tissue-engineered constructs, cell-based therapy, micro-fracture, mosaicplasty, autologous chondrocyte implantation (aci), matrix-induced autologous chondrocyte implantation (maci)

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