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      Priming strategies for controlling stem cell fate: Applications and challenges in dental tissue regeneration

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          Abstract

          Mesenchymal stromal cells (MSCs) have attracted intense interest in the field of dental tissue regeneration. Dental tissue is a popular source of MSCs because MSCs can be obtained with minimally invasive procedures. MSCs possess distinct inherent properties of self-renewal, immunomodulation, proangiogenic potential, and multilineage potency, as well as being readily available and easy to culture. However, major issues, including poor engraftment and low survival rates in vivo, remain to be resolved before large-scale application is feasible in clinical treatments. Thus, some recent investigations have sought ways to optimize MSC functions in vitro and in vivo. Currently, priming culture conditions, pretreatment with mechanical and physical stimuli, preconditioning with cytokines and growth factors, and genetic modification of MSCs are considered to be the main strategies; all of which could contribute to improving MSC efficacy in dental regenerative medicine. Research in this field has made tremendous progress and continues to gather interest and stimulate innovation. In this review, we summarize the priming approaches for enhancing the intrinsic biological properties of MSCs such as migration, antiapoptotic effect, proangiogenic potential, and regenerative properties. Challenges in current approaches associated with MSC modification and possible future solutions are also indicated. We aim to outline the present understanding of priming approaches to improve the therapeutic effects of MSCs on dental tissue regeneration.

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          Most cited references184

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          Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

          The considerable therapeutic potential of human multipotent mesenchymal stromal cells (MSC) has generated markedly increasing interest in a wide variety of biomedical disciplines. However, investigators report studies of MSC using different methods of isolation and expansion, and different approaches to characterizing the cells. Thus it is increasingly difficult to compare and contrast study outcomes, which hinders progress in the field. To begin to address this issue, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC. First, MSC must be plastic-adherent when maintained in standard culture conditions. Second, MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. Third, MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro. While these criteria will probably require modification as new knowledge unfolds, we believe this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.
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            Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo.

            Dentinal repair in the postnatal organism occurs through the activity of specialized cells, odontoblasts, that are thought to be maintained by an as yet undefined precursor population associated with pulp tissue. In this study, we isolated a clonogenic, rapidly proliferative population of cells from adult human dental pulp. These DPSCs were then compared with human bone marrow stromal cells (BMSCs), known precursors of osteoblasts. Although they share a similar immunophenotype in vitro, functional studies showed that DPSCs produced only sporadic, but densely calcified nodules, and did not form adipocytes, whereas BMSCs routinely calcified throughout the adherent cell layer with clusters of lipid-laden adipocytes. When DPSCs were transplanted into immunocompromised mice, they generated a dentin-like structure lined with human odontoblast-like cells that surrounded a pulp-like interstitial tissue. In contrast, BMSCs formed lamellar bone containing osteocytes and surface-lining osteoblasts, surrounding a fibrous vascular tissue with active hematopoiesis and adipocytes. This study isolates postnatal human DPSCs that have the ability to form a dentin/pulp-like complex.
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              Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities

              Mesenchymal stromal cells (MSCs) have been the subject of clinical trials for more than a generation, and the outcomes of advanced clinical trials have fallen short of expectations raised by encouraging pre-clinical animal data in a wide array of disease models. In this Perspective, important biological and pharmacological disparities in pre-clinical research and human translational studies are highlighted, and analyses of clinical trial failures and recent successes provide a rational pathway to MSC regulatory approval and deployment for disorders with unmet medical needs.
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                Author and article information

                Contributors
                Journal
                World J Stem Cells
                WJSC
                World Journal of Stem Cells
                Baishideng Publishing Group Inc
                1948-0210
                26 November 2021
                26 November 2021
                : 13
                : 11
                : 1625-1646
                Affiliations
                State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
                Department of Oral Radiology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
                State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
                Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
                Author notes

                Author contributions: Zhang SY drafted the manuscript; Ren JY drew the figures and revised the manuscript; Yang B proposed the ideas and revised the manuscript; All authors have read and approved the final manuscript.

                Supported by Applied Basic Research Programs of Science and Technology Department of Sichuan Province, No. 2021YJ0147; and National Natural Science Foundation of China, No. 31600789.

                Corresponding author: Bo Yang, DDS, PhD, Academic Fellow, State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14 3rd Section, Renmin South Road, Chengdu 610041, Sichuan Province, China. dr.yangbo@ 123456scu.edu.cn

                Article
                jWJSC.v13.i11.pg1625
                10.4252/wjsc.v13.i11.1625
                8641023
                34909115
                93356c67-9267-4390-a033-7cc00512ed69
                ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/

                History
                : 27 February 2021
                : 14 May 2021
                : 27 August 2021
                Categories
                Review

                mesenchymal stem cells,priming,dental regeneration,culture conditions,cytokines,growth factors,genetic modification

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