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      Characteristics and Therapeutic Potential of Dental Pulp Stem Cells on Neurodegenerative Diseases

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          Abstract

          To evaluate the therapeutic potential of stem cells for neurodegenerative diseases, emphasis should be placed on clarifying the characteristics of the various types of stem cells. Among stem cells, dental pulp stem cells (DPSCs) are a cell population that is rich in cell proliferation and multipotency. It has been reported that transplantation of DPSCs has protective effects against models of neurodegenerative diseases. The protective effects are not only through differentiation into the target cell type for the disease but are also related to trophic factors released from DPSCs. Recently, it has been reported that serum-free culture supernatant of dental pulp stem cell-conditioned medium (DPCM) contains various trophic factors and cytokines and that DPCM is effective for models of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS). Moreover, the use of stem cells from human exfoliated deciduous teeth (SHEDs) has been considered. SHEDs are derived from deciduous teeth that have been disposed of as medical waste. SHEDs have higher differentiation capacity and proliferation ability than DPSCs. In addition, the serum-free culture supernatant of SHEDs (SHED-CM) contains more trophic factors, cytokines, and biometals than DPCM and also promotes neuroprotection. The neuroprotective effect of DPSCs, including those from deciduous teeth, will be used as the seeds of therapeutic drugs for neurodegenerative diseases. SHEDs will be used for further cell therapy of neurodegenerative diseases in the future. In this paper, we focused on the characteristics of DPSCs and their potential for neurodegenerative diseases.

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          Most cited references42

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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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            Stem cell properties of human dental pulp stem cells.

            In this study, we characterized the self-renewal capability, multi-lineage differentiation capacity, and clonogenic efficiency of human dental pulp stem cells (DPSCs). DPSCs were capable of forming ectopic dentin and associated pulp tissue in vivo. Stromal-like cells were reestablished in culture from primary DPSC transplants and re-transplanted into immunocompromised mice to generate a dentin-pulp-like tissue, demonstrating their self-renewal capability. DPSCs were also found to be capable of differentiating into adipocytes and neural-like cells. The odontogenic potential of 12 individual single-colony-derived DPSC strains was determined. Two-thirds of the single-colony-derived DPSC strains generated abundant ectopic dentin in vivo, while only a limited amount of dentin was detected in the remaining one-third. These results indicate that single-colony-derived DPSC strains differ from each other with respect to their rate of odontogenesis. Taken together, these results demonstrate that DPSCs possess stem-cell-like qualities, including self-renewal capability and multi-lineage differentiation.
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              Parkinson's disease. Second of two parts.

              At no time in the past have the basic and clinical sciences applied to Parkinson's disease been so active. Experimental therapies under study at present promise to improve on the limitations of existing treatments. Future progress in understanding the causation and pathogenesis of the disorder will permit the development of new treatments that will slow, halt, or even reverse the currently inexorable progressive course of Parkinson's disease.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                07 May 2020
                2020
                : 14
                : 407
                Affiliations
                Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University , Gifu, Japan
                Author notes

                Edited by: Asuka Morizane, Kyoto University, Japan

                Reviewed by: Jihwan Song, CHA University, South Korea; Keiji Masuda, Kyushu University, Japan

                *Correspondence: Isao Hozumi, hozumi@ 123456gifu-pu.ac.jp

                This article was submitted to Neuropharmacology, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2020.00407
                7222959
                32457568
                33b19ff1-b24f-484d-be29-138f1fc04e24
                Copyright © 2020 Ueda, Inden, Ito, Kurita and Hozumi.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 February 2020
                : 03 April 2020
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 54, Pages: 7, Words: 0
                Categories
                Neuroscience
                Mini Review

                Neurosciences
                dental pulp stem cells,stem cells from human exfoliated deciduous teeth,conditioned medium,neurodegenerative disease,cell therapy

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