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      Human Oral Stem Cells, Biomaterials and Extracellular Vesicles: A Promising Tool in Bone Tissue Repair

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          Abstract

          Tissue engineering and/or regenerative medicine are fields of life science exploiting both engineering and biological fundamentals to originate new tissues and organs and to induce the regeneration of damaged or diseased tissues and organs. In particular, de novo bone tissue regeneration requires a mechanically competent osteo-conductive/inductive 3D biomaterial scaffold that guarantees the cell adhesion, proliferation, angiogenesis and differentiation into osteogenic lineage. Cellular components represent a key factor in tissue engineering and bone growth strategies take advantage from employment of mesenchymal stem cells (MSCs), an ideal cell source for tissue repair. Recently, the application of extracellular vesicles (EVs), isolated from stem cells, as cell-free therapy has emerged as a promising therapeutic strategy. This review aims at summarizing the recent and representative research on the bone tissue engineering field using a 3D scaffold enriched with human oral stem cells and their derivatives, EVs, as a promising therapeutic potential in the reconstructing of bone tissue defects.

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          Most cited references 80

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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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            Investigation of multipotent postnatal stem cells from human periodontal ligament.

            Periodontal diseases that lead to the destruction of periodontal tissues--including periodontal ligament (PDL), cementum, and bone--are a major cause of tooth loss in adults and are a substantial public-health burden worldwide. PDL is a specialised connective tissue that connects cementum and alveolar bone to maintain and support teeth in situ and preserve tissue homoeostasis. We investigated the notion that human PDL contains stem cells that could be used to regenerate periodontal tissue. PDL tissue was obtained from 25 surgically extracted human third molars and used to isolate PDL stem cells (PDLSCs) by single-colony selection and magnetic activated cell sorting. Immunohistochemical staining, RT-PCR, and northern and western blot analyses were used to identify putative stem-cell markers. Human PDLSCs were transplanted into immunocompromised mice (n=12) and rats (n=6) to assess capacity for tissue regeneration and periodontal repair. Findings PDLSCs expressed the mesenchymal stem-cell markers STRO-1 and CD146/MUC18. Under defined culture conditions, PDLSCs differentiated into cementoblast-like cells, adipocytes, and collagen-forming cells. When transplanted into immunocompromised rodents, PDLSCs showed the capacity to generate a cementum/PDL-like structure and contribute to periodontal tissue repair. Our findings suggest that PDL contains stem cells that have the potential to generate cementum/PDL-like tissue in vivo. Transplantation of these cells, which can be obtained from an easily accessible tissue resource and expanded ex vivo, might hold promise as a therapeutic approach for reconstruction of tissues destroyed by periodontal diseases.
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              Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles

              Release of membrane vesicles, a process conserved in both prokaryotes and eukaryotes, represents an evolutionary link, and suggests essential functions of a dynamic extracellular vesicular compartment (including exosomes, microparticles or microvesicles and apoptotic bodies). Compelling evidence supports the significance of this compartment in a broad range of physiological and pathological processes. However, classification of membrane vesicles, protocols of their isolation and detection, molecular details of vesicular release, clearance and biological functions are still under intense investigation. Here, we give a comprehensive overview of extracellular vesicles. After discussing the technical pitfalls and potential artifacts of the rapidly emerging field, we compare results from meta-analyses of published proteomic studies on membrane vesicles. We also summarize clinical implications of membrane vesicles. Lessons from this compartment challenge current paradigms concerning the mechanisms of intercellular communication and immune regulation. Furthermore, its clinical implementation may open new perspectives in translational medicine both in diagnostics and therapy.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                09 October 2019
                October 2019
                : 20
                : 20
                Affiliations
                [1 ]Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; guya.marconi@ 123456unich.it (G.D.M.); sante.pierdomenico@ 123456unich.it (S.D.P.); adriano.piattelli@ 123456unich.it (A.P.); francesca.diomede@ 123456unich.it (F.D.); jacopo.pizzicannella@ 123456unich.it (J.P.)
                [2 ]ASL02 Lanciano-Vasto-Chieti, Ss. Annunziata Hospital, 66100 Chieti, Italy
                Author notes
                [* ]Correspondence: trubiani@ 123456unich.it ; Tel.: +39-0871-3554097
                [†]

                These authors contributed equally to this work.

                Article
                ijms-20-04987
                10.3390/ijms20204987
                6834314
                31600975
                © 2019 by the authors.

                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/).

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