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      Wound Healing and Cell Dynamics Including Mesenchymal and Dental Pulp Stem Cells Induced by Photobiomodulation Therapy: An Example of Socket-Preserving Effects after Tooth Extraction in Rats and a Literature Review

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          Abstract

          High-intensity laser therapy (HILT) and photobiomodulation therapy (PBMT) are two types of laser treatment. According to recent clinical reports, PBMT promotes wound healing after trauma or surgery. In addition, basic research has revealed that cell differentiation, proliferation, and activity and subsequent tissue activation and wound healing can be promoted. However, many points remain unclear regarding the mechanisms for wound healing induced by PBMT. Therefore, in this review, we present an example from our study of HILT and PBMT irradiation of tooth extraction wounds using two types of lasers with different characteristics (diode laser and carbon dioxide laser). Then, the effects of PBMT on the wound healing of bone tissues are reviewed from histological, biochemical, and cytological perspectives on the basis of our own study of the extraction socket as well as studies by other researchers. Furthermore, we consider the feasibility of treatment in which PBMT irradiation is applied to stem cells including dental pulp stem cells, the theme of this Special Issue, and we discuss research that has been reported on its effect.

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          Most cited references72

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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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            Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy.

            Photobiomodulation (PBM) also known as low-level laser (or light) therapy (LLLT), has been known for almost 50 years but still has not gained widespread acceptance, largely due to uncertainty about the molecular, cellular, and tissular mechanisms of action. However, in recent years, much knowledge has been gained in this area, which will be summarized in this review. One of the most important chromophores is cytochrome c oxidase (unit IV in the mitochondrial respiratory chain), which contains both heme and copper centers and absorbs light into the near-infra-red region. The leading hypothesis is that the photons dissociate inhibitory nitric oxide from the enzyme, leading to an increase in electron transport, mitochondrial membrane potential and ATP production. Another hypothesis concerns light-sensitive ion channels that can be activated allowing calcium to enter the cell. After the initial photon absorption events, numerous signaling pathways are activated via reactive oxygen species, cyclic AMP, NO and Ca2+, leading to activation of transcription factors. These transcription factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT.
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              Spontaneous human adult stem cell transformation.

              Human adult stem cells are being evaluated widely for various therapeutic approaches. Several recent clinical trials have reported their safety, showing them to be highly resistant to transformation. The clear similarities between stem cell and cancer stem cell genetic programs are nonetheless the basis of a recent proposal that some cancer stem cells could derive from human adult stem cells. Here we show that although they can be managed safely during the standard ex vivo expansion period (6-8 weeks), human mesenchymal stem cells can undergo spontaneous transformation following long-term in vitro culture (4-5 months). This is the first report of spontaneous transformation of human adult stem cells, supporting the hypothesis of cancer stem cell origin. Our findings indicate the importance of biosafety studies of mesenchymal stem cell biology to efficiently exploit their full clinical therapeutic potential.
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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
                18 September 2020
                September 2020
                : 21
                : 18
                : 6850
                Affiliations
                [1 ]Department of Geriatric Dentistry, Osaka Dental University, Osaka 546-0032, Japan; kazuya-t@ 123456cc.osaka-dent.ac.jp
                [2 ]Department of Anesthesiology, Osaka Dental University, Osaka 540-0008, Japan; daigou_e0120@ 123456yahoo.co.jp
                [3 ]Fukuoka Dental Office, Satsuma-gun, Kagoshima 895-1811, Japan; hn-fukuoka@ 123456po4.synapse.ne.jp (H.F.); nobuko-aoki@ 123456hotmail.co.jp (N.F.)
                [4 ]Bees Dental Office, Fukuoka City, Fukuoka 814-0106, Japan; beezaemonn@ 123456yahoo.co.jp
                Author notes
                [* ]Correspondence: qpmayo24@ 123456yahoo.co.jp ; Tel.: +81-6-6910-1111
                Author information
                https://orcid.org/0000-0003-3032-3989
                Article
                ijms-21-06850
                10.3390/ijms21186850
                7555322
                32961958
                574d85a3-e28f-494d-80db-c7c42c082f0b
                © 2020 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/).

                History
                : 05 August 2020
                : 17 September 2020
                Categories
                Review

                Molecular biology
                co2 laser,diode laser,tooth extraction,socket preservation,extraction socket,photobiomodulation therapy,high-intensity laser therapy,wound healing

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