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      Dental Pulp Stem Cells for Bone Tissue Engineering: A Literature Review

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          Abstract

          Bone tissue engineering (BTE) is a promising approach for repairing and regenerating damaged bone tissue, using stem cells and scaffold structures. Among various stem cell sources, dental pulp stem cells (DPSCs) have emerged as a potential candidate due to their multipotential capabilities, ability to undergo osteogenic differentiation, low immunogenicity, and ease of isolation. This article reviews the biological characteristics of DPSCs, their potential for BTE, and the underlying transcription factors and signaling pathways involved in osteogenic differentiation; it also highlights the application of DPSCs in inducing scaffold tissues for bone regeneration and summarizes animal and clinical studies conducted in this field. This review demonstrates the potential of DPSC-based BTE for effective bone repair and regeneration, with implications for clinical translation.

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          Most cited references156

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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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            SHED: stem cells from human exfoliated deciduous teeth.

            To isolate high-quality human postnatal stem cells from accessible resources is an important goal for stem-cell research. In this study we found that exfoliated human deciduous tooth contains multipotent stem cells [stem cells from human exfoliated deciduous teeth (SHED)]. SHED were identified to be a population of highly proliferative, clonogenic cells capable of differentiating into a variety of cell types including neural cells, adipocytes, and odontoblasts. After in vivo transplantation, SHED were found to be able to induce bone formation, generate dentin, and survive in mouse brain along with expression of neural markers. Here we show that a naturally exfoliated human organ contains a population of stem cells that are completely different from previously identified stem cells. SHED are not only derived from a very accessible tissue resource but are also capable of providing enough cells for potential clinical application. Thus, exfoliated teeth may be an unexpected unique resource for stem-cell therapies including autologous stem-cell transplantation and tissue engineering.
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              Bone regeneration strategies: Engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives

              Bone fractures are the most common traumatic injuries in humans. The repair of bone fractures is a regenerative process that recapitulates many of the biological events of embryonic skeletal development. Most of the time it leads to successful healing and the recovery of the damaged bone. Unfortunately, about 5-10% of fractures will lead to delayed healing or non-union, more so in the case of co-morbidities such as diabetes. In this article, we review the different strategies to heal bone defects using synthetic bone graft substitutes and biologically active substances or stem cells. Our review is different from previous reviews, which focus on strategies that are still at the early stages of development and use mostly in vitro experiments with cell lines or stem cells. Here, we focus on what is already implemented in the clinics, what is currently in clinical trials, and what has been tested in animal models. Treatment approaches can be classified in three major categories: i) synthetic bone graft substitutes (BGS) whose architecture and surface can be optimized; ii) BGS combined with bioactive molecules such as growth factors, peptides or small molecules targeting bone precursor cells, bone formation and metabolism; iii) cell-based strategies with progenitor cells combined or not with active molecules that can be injected or seeded on BGS for improved delivery. We review the major types of adult stromal cells (bone marrow, adipose and periosteum derived) that have been used and compare their properties. Finally, we discuss the remaining challenges that need to be addressed to significantly improve the healing of bone defects.
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                Author and article information

                Contributors
                Journal
                Stem Cells Int
                Stem Cells Int
                sci
                Stem Cells International
                Hindawi
                1687-966X
                1687-9678
                2023
                11 October 2023
                : 2023
                : 7357179
                Affiliations
                1Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
                2Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
                Author notes

                Academic Editor: Isotta Chimenti

                Author information
                https://orcid.org/0000-0002-7447-3826
                https://orcid.org/0009-0003-5174-7534
                https://orcid.org/0000-0001-6057-0804
                https://orcid.org/0009-0007-8036-6633
                https://orcid.org/0000-0002-1308-4827
                https://orcid.org/0000-0001-9215-3845
                Article
                10.1155/2023/7357179
                10586346
                37868704
                f92eb881-3c44-4a4a-bbad-888db8ef9031
                Copyright © 2023 Xiaolei Bai et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 1 March 2023
                : 3 June 2023
                : 19 September 2023
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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