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      Concise Review: Periodontal Tissue Regeneration Using Stem Cells: Strategies and Translational Considerations

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          Abstract

          Periodontitis is a widespread disease characterized by inflammation‐induced progressive damage to the tooth‐supporting structures until tooth loss occurs. The regeneration of lost/damaged support tissue in the periodontium, including the alveolar bone, periodontal ligament, and cementum, is an ambitious purpose of periodontal regenerative therapy and might effectively reduce periodontitis‐caused tooth loss. The use of stem cells for periodontal regeneration is a hot field in translational research and an emerging potential treatment for periodontitis. This concise review summarizes the regenerative approaches using either culture‐expanded or host‐mobilized stem cells that are currently being investigated in the laboratory and with preclinical models for periodontal tissue regeneration and highlights the most recent evidence supporting their translational potential toward a widespread use in the clinic for combating highly prevalent periodontal disease. We conclude that in addition to in vitro cell‐biomaterial design and transplantation, the engineering of biomaterial devices to encourage the innate regenerative capabilities of the periodontium warrants further investigation. In comparison to cell‐based therapies, the use of biomaterials is comparatively simple and sufficiently reliable to support high levels of endogenous tissue regeneration. Thus, endogenous regenerative technology is a more economical and effective as well as safer method for the treatment of clinical patients. stem cells translational medicine 2019;8:392–403

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          Most cited references74

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          Periodontitis: a polymicrobial disruption of host homeostasis.

          Periodontitis, or gum disease, affects millions of people each year. Although it is associated with a defined microbial composition found on the surface of the tooth and tooth root, the contribution of bacteria to disease progression is poorly understood. Commensal bacteria probably induce a protective response that prevents the host from developing disease. However, several bacterial species found in plaque (the 'red-complex' bacteria: Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) use various mechanisms to interfere with host defence mechanisms. Furthermore, disease may result from 'community-based' attack on the host. Here, I describe the interaction of the host immune system with the oral bacteria in healthy states and in diseased states.
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            Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine.

            To date, 5 different human dental stem/progenitor cells have been isolated and characterized: dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAP), and dental follicle progenitor cells (DFPCs). These postnatal populations have mesenchymal-stem-cell-like (MSC) qualities, including the capacity for self-renewal and multilineage differentiation potential. MSCs derived from bone marrow (BMMSCs) are capable of giving rise to various lineages of cells, such as osteogenic, chondrogenic, adipogenic, myogenic, and neurogenic cells. The dental-tissue-derived stem cells are isolated from specialized tissue with potent capacities to differentiate into odontogenic cells. However, they also have the ability to give rise to other cell lineages similar to, but different in potency from, that of BMMSCs. This article will review the isolation and characterization of the properties of different dental MSC-like populations in comparison with those of other MSCs, such as BMMSCs. Important issues in stem cell biology, such as stem cell niche, homing, and immunoregulation, will also be discussed.
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              Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds.

              In normal tissue repair, macrophages exhibit a pro-inflammatory phenotype (M1) at early stages and a pro-healing phenotype (M2) at later stages. We have previously shown that M1 macrophages initiate angiogenesis while M2 macrophages promote vessel maturation. Therefore, we reasoned that scaffolds that promote sequential M1 and M2 polarization of infiltrating macrophages should result in enhanced angiogenesis and healing. To this end, we first analyzed the in vitro kinetics of macrophage phenotype switch using flow cytometry, gene expression, and cytokine secretion analysis. Then, we designed scaffolds for bone regeneration based on modifications of decellularized bone for a short release of interferon-gamma (IFNg) to promote the M1 phenotype, followed by a more sustained release of interleukin-4 (IL4) to promote the M2 phenotype. To achieve this sequential release profile, IFNg was physically adsorbed onto the scaffolds, while IL4 was attached via biotin-streptavidin binding. Interestingly, despite the strong interactions between biotin and streptavidin, release studies showed that biotinylated IL4 was released over 6 days. These scaffolds promoted sequential M1 and M2 polarization of primary human macrophages as measured by gene expression of ten M1 and M2 markers and secretion of four cytokines, although the overlapping phases of IFNg and IL4 release tempered polarization to some extent. Murine subcutaneous implantation model showed increased vascularization in scaffolds releasing IFNg compared to controls. This study demonstrates that scaffolds for tissue engineering can be designed to harness the angiogenic behavior of host macrophages towards scaffold vascularization.
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                Author and article information

                Contributors
                sunhaihua1972225@163.com
                cfmsunhh@fmmu.edu.cn
                Journal
                Stem Cells Transl Med
                Stem Cells Transl Med
                10.1002/(ISSN)2157-6580
                SCT3
                Stem Cells Translational Medicine
                John Wiley & Sons, Inc. (Hoboken, USA )
                2157-6564
                2157-6580
                26 December 2018
                April 2019
                : 8
                : 4 ( doiID: 10.1002/sct3.2019.8.issue-4 )
                : 392-403
                Affiliations
                [ 1 ] State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology Fourth Military Medical University Xi'an People's Republic of China
                Author notes
                [*] [* ]Correspondence: Fa‐Ming Chen, Ph.D., State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 145th West Changle Road, Xi'an 710032, People's Republic of China. Telephone: 86‐29‐84776096; e‐mail: cfmsunhh@ 123456fmmu.edu.cn ; or Hai‐Hua Sun, Ph.D., State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 145th West Changle Road, Xi'an 710032, People's Republic of China. Telephone: 86‐29‐84776094; e‐mail: sunhaihua1972225@ 123456163.com
                [†]

                Contributed equally

                Author information
                https://orcid.org/0000-0001-7434-690X
                https://orcid.org/0000-0002-8398-2104
                Article
                SCT312443
                10.1002/sctm.18-0181
                6431686
                30585445
                3ee40b86-6665-4d9d-baff-89a5281f9b94
                © 2018 The Authors stem cells translational medicine 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-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 17 August 2018
                : 22 November 2018
                Page count
                Figures: 6, Tables: 1, Pages: 12, Words: 8821
                Funding
                Funded by: National Key Research and Development Program of China
                Award ID: 2018YFC1105204
                Funded by: National Natural Science Foundation of China
                Award ID: 81530050
                Funded by: Shaanxi Key Scientific and Technological Innovation Team
                Award ID: 2017KCT‐32
                Funded by: Changjiang Scholars Program of the Ministry of Education of the People's Republic of China (2016)
                Categories
                Tissue Engineering and Regenerative Medicine
                Tissue Engineering and Regenerative Medicine
                Custom metadata
                2.0
                sct312443
                April 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.1 mode:remove_FC converted:25.03.2019

                periodontal regeneration,cell transplantation,cell homing,biomaterials,tissue engineering,endogenous regeneration

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