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      Potential Roles of Dental Pulp Stem Cells in Neural Regeneration and Repair

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          Abstract

          This review summarizes current advances in dental pulp stem cells (DPSCs) and their potential applications in the nervous diseases. Injured adult mammalian nervous system has a limited regenerative capacity due to an insufficient pool of precursor cells in both central and peripheral nervous systems. Nerve growth is also constrained by inhibitory factors (associated with central myelin) and barrier tissues (glial scarring). Stem cells, possessing the capacity of self-renewal and multicellular differentiation, promise new therapeutic strategies for overcoming these impediments to neural regeneration. Dental pulp stem cells (DPSCs) derive from a cranial neural crest lineage, retain a remarkable potential for neuronal differentiation, and additionally express multiple factors that are suitable for neuronal and axonal regeneration. DPSCs can also express immunomodulatory factors that stimulate formation of blood vessels and enhance regeneration and repair of injured nerve. These unique properties together with their ready accessibility make DPSCs an attractive cell source for tissue engineering in injured and diseased nervous systems. In this review, we interrogate the neuronal differentiation potential as well as the neuroprotective, neurotrophic, angiogenic, and immunomodulatory properties of DPSCs and its application in the injured nervous system. Taken together, DPSCs are an ideal stem cell resource for therapeutic approaches to neural repair and regeneration in nerve diseases.

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          Most cited references152

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          Alzheimer's disease: strategies for disease modification.

          Alzheimer's disease is the largest unmet medical need in neurology. Current drugs improve symptoms, but do not have profound disease-modifying effects. However, in recent years, several approaches aimed at inhibiting disease progression have advanced to clinical trials. Among these, strategies targeting the production and clearance of the amyloid-beta peptide - a cardinal feature of Alzheimer's disease that is thought to be important in disease pathogenesis - are the most advanced. Approaches aimed at modulating the abnormal aggregation of tau filaments (another key feature of the disease), and those targeting metabolic dysfunction, are also being evaluated in the clinic. This article discusses recent progress with each of these strategies, with a focus on anti-amyloid strategies, highlighting the lessons learned and the challenges that remain.
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            Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study.

            Mesenchymal stem cells (MSCs) have been isolated from the pulp tissue of permanent teeth (dental pulp stem cells or DPSCs) and deciduous teeth (stem cells from human exfoliated deciduous teeth). We recently discovered another type of MSCs in the apical papilla of human immature permanent teeth termed stem cells from the apical papilla (SCAP). Here, we further characterized the apical papilla tissue and stem cell properties of SCAP using histologic, immunohistochemical, and immunocytofluorescent analyses. We found that the apical papilla is distinctive to the pulp in terms of containing less cellular and vascular components than those in the pulp. Cells in the apical papilla proliferated 2- to 3-fold greater than those in the pulp in organ cultures. Both SCAP and DPSCs were as potent in osteo/dentinogenic differentiation as MSCs from bone marrows, whereas they were weaker in adipogenic potential. The immunophenotype of SCAP is similar to that of DPSCs on the osteo/dentinogenic and growth factor receptor gene profiles. Double-staining experiments showed that STRO-1 coexpressed with dentinogenic markers such as bone sialophosphoprotein, osteocalcin, and growth factors FGFR1 and TGFbetaRI in cultured SCAP. Additionally, SCAP express a wide variety of neurogenic markers such as nestin and neurofilament M upon stimulation with a neurogenic medium. We conclude that SCAP are similar to DPSCs but a distinct source of potent dental stem/progenitor cells. Their implications in root development and apexogenesis are discussed.
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              Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis.

              Neural crest cells are multipotential stem cells that contribute extensively to vertebrate development and give rise to various cell and tissue types. Determination of the fate of mammalian neural crest has been inhibited by the lack of appropriate markers. Here, we make use of a two-component genetic system for indelibly marking the progeny of the cranial neural crest during tooth and mandible development. In the first mouse line, Cre recombinase is expressed under the control of the Wnt1 promoter as a transgene. Significantly, Wnt1 transgene expression is limited to the migrating neural crest cells that are derived from the dorsal CNS. The second mouse line, the ROSA26 conditional reporter (R26R), serves as a substrate for the Cre-mediated recombination. Using this two-component genetic system, we have systematically followed the migration and differentiation of the cranial neural crest (CNC) cells from E9.5 to 6 weeks after birth. Our results demonstrate, for the first time, that CNC cells contribute to the formation of condensed dental mesenchyme, dental papilla, odontoblasts, dentine matrix, pulp, cementum, periodontal ligaments, chondrocytes in Meckel's cartilage, mandible, the articulating disc of temporomandibular joint and branchial arch nerve ganglia. More importantly, there is a dynamic distribution of CNC- and non-CNC-derived cells during tooth and mandibular morphogenesis. These results are a first step towards a comprehensive understanding of neural crest cell migration and differentiation during mammalian craniofacial development. Furthermore, this transgenic model also provides a new tool for cell lineage analysis and genetic manipulation of neural-crest-derived components in normal and abnormal embryogenesis.
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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
                2018
                7 May 2018
                : 2018
                : 1731289
                Affiliations
                1WMU-UQ Group for Regenerative Medicine, Institute of Stem Cells and Tissue Engineering, School of Stomatology, Wenzhou Medical University, Wenzhou 325035, China
                2School of Dentistry, The University of Queensland, Herston, QLD 4006, Australia
                3School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
                4School of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325035, China
                5Wenzhou Institute of Biomaterials and Engineering, CAS, Wenzhou 325011, China
                6Engineering Research Center of Clinical Functional Materials and Diagnosis & Treatment Devices of Zhejiang Province, Wenzhou Institute of Biomaterials and Engineering, CAS, Wenzhou 325011, China
                Author notes

                Academic Editor: Tao-Sheng Li

                Author information
                http://orcid.org/0000-0002-0949-8525
                http://orcid.org/0000-0002-6151-6479
                http://orcid.org/0000-0002-2868-9247
                Article
                10.1155/2018/1731289
                5964589
                a591119a-9451-45cb-ba5d-5bd78f946cf6
                Copyright © 2018 Lihua Luo 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
                : 7 November 2017
                : 22 March 2018
                Funding
                Funded by: Research and Development Program Project of Xiangyang
                Award ID: 20270268020
                Funded by: Wenzhou Medical University
                Award ID: QTJ16026
                Funded by: UQDVCR
                Award ID: 610709
                Funded by: National Natural Science Foundation of China
                Award ID: 81601626
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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