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      Advances in mesenchymal stem cell conditioned medium-mediated periodontal tissue regeneration

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          Abstract

          Periodontitis is a chronic inflammatory disease that leads to the destruction of both soft and hard periodontal tissues. Complete periodontal regeneration in clinics using the currently available treatment approaches is still a challenge. Mesenchymal stem cells (MSCs) have shown promising potential to regenerate periodontal tissue in various preclinical and clinical studies. The poor survival rate of MSCs during in vivo transplantation and host immunogenic reaction towards MSCs are the main drawbacks of direct use of MSCs in periodontal tissue regeneration. Autologous MSCs have limited sources and possess patient morbidity during harvesting. Direct use of allogenic MSCs could induce host immune reaction. Therefore, the MSC-based indirect treatment approach could be beneficial for periodontal regeneration in clinics. MSC culture conditioned medium (CM) contains secretomes that had shown immunomodulatory and tissue regenerative potential in pre-clinical and clinical studies. MSC-CM contains a cocktail of growth factors, cytokines, chemokines, enzymes, and exosomes, extracellular vesicles, etc. MSC-CM-based indirect treatment has the potential to eliminate the drawbacks of direct use of MSCs for periodontal tissue regeneration. MSC-CM holds the tremendous potential of bench-to-bed translation in periodontal regeneration applications. This review focuses on the accumulating evidence indicating the therapeutic potential of the MSC-CM in periodontal regeneration-related pre-clinical and clinical studies. Recent advances on MSC-CM-based periodontal regeneration, existing challenges, and prospects are well summarized as guidance to improve the effectiveness of MSC-CM on periodontal regeneration in clinics.

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          Most cited references126

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          Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone.

          The mammalian skeletal system harbours a hierarchical system of mesenchymal stem cells, osteoprogenitors and osteoblasts sustaining lifelong bone formation. Osteogenesis is indispensable for the homeostatic renewal of bone as well as regenerative fracture healing, but these processes frequently decline in ageing organisms, leading to loss of bone mass and increased fracture incidence. Evidence indicates that the growth of blood vessels in bone and osteogenesis are coupled, but relatively little is known about the underlying cellular and molecular mechanisms. Here we identify a new capillary subtype in the murine skeletal system with distinct morphological, molecular and functional properties. These vessels are found in specific locations, mediate growth of the bone vasculature, generate distinct metabolic and molecular microenvironments, maintain perivascular osteoprogenitors and couple angiogenesis to osteogenesis. The abundance of these vessels and associated osteoprogenitors was strongly reduced in bone from aged animals, and pharmacological reversal of this decline allowed the restoration of bone mass.
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            Periodontitis: from microbial immune subversion to systemic inflammation.

            Periodontitis is a dysbiotic inflammatory disease with an adverse impact on systemic health. Recent studies have provided insights into the emergence and persistence of dysbiotic oral microbial communities that can mediate inflammatory pathology at local as well as distant sites. This Review discusses the mechanisms of microbial immune subversion that tip the balance from homeostasis to disease in oral or extra-oral sites.
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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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                Author and article information

                Contributors
                2020686041@gzhmu.edu.cn
                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central (London )
                1479-5876
                4 November 2021
                4 November 2021
                2021
                : 19
                : 456
                Affiliations
                [1 ]GRID grid.410737.6, ISNI 0000 0000 8653 1072, Department of Periodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, , Guangzhou Key laboratory of Basic and Applied Research of Oral Regenerative Medicine, ; Guangzhou, Guangdong 510182 China
                [2 ]GRID grid.64924.3d, ISNI 0000 0004 1760 5735, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, , Jilin University, ; Changchun, Jilin 130021 People’s Republic of China
                [3 ]GRID grid.410737.6, ISNI 0000 0000 8653 1072, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, , Affiliated Stomatology Hospital of Guangzhou Medical University, ; Guangzhou, China
                [4 ]GRID grid.411847.f, ISNI 0000 0004 1804 4300, Vascular Biology Research Institute, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, ; Guangzhou, China
                Article
                3125
                10.1186/s12967-021-03125-5
                8567704
                34736500
                4962708b-f0cc-4468-87c9-4822aac5b80e
                © The Author(s) 2021

                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
                : 31 July 2021
                : 22 October 2021
                Funding
                Funded by: medical support program of the jilin university
                Award ID: 20170311032YY
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100009991, department of finance of jilin province;
                Award ID: jcsz2020304-9
                Award ID: jsz2018170-12
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, national natural science foundation of china;
                Award ID: 81970946
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                Medicine
                periodontal tissue regeneration,mesenchymal stem cells conditioned medium,osteogenesis,immunomodulation,angiogenesis,chemotaxis

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