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Nikolic S, Alastra G, Pultar F, Lüthy L, Stadlinger B, Carreira EM, Bugueno IM, Mitsiadis TA. Mutanobactin-D, a Streptococcus mutans Non-Ribosomal Cyclic Lipopeptide, Induces Osteogenic/Odontogenic Differentiation of Human Dental Pulp Stem Cells and Human Bone Marrow Stem Cells. Int J Mol Sci 2025; 26:1144. [PMID: 39940912 PMCID: PMC11817755 DOI: 10.3390/ijms26031144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/09/2025] [Accepted: 01/26/2025] [Indexed: 02/16/2025] Open
Abstract
Bacterium-triggered carious lesions implicate dental hard tissue destruction and the simultaneous initiation of regenerative events comprising dental stem cell activation. Streptococcus mutans (S. mutans) is a prominent pathogen of the oral cavity and the principal cause of caries. S. mutans generates complex products involved in interbacterial interactions, including Mutanobactin-D (Mub-D), which belongs to a group of non-ribosomal cyclic lipopeptides. In the present study, we aimed to analyse the potential role of the synthetic Mub-D peptide in cell populations involved in tissue regenerative processes. To this end, we assessed the in vitro effects of Mub-D in human dental pulp stem cells (hDPSCs) and human bone marrow stem cells (hBMSCs). Our data demonstrated a concentration-dependent effect of Mub-D on their viability and a significant increase in their proliferation and osteogenic/odontogenic differentiation. These events were associated with specific changes in gene expression, where CCDN-1, RUNX-2, OSX, OCN, DMP-1, DSPP, and BMP-2 genes were upregulated. The ability of Mub-D to modulate the osteogenic/odontogenic differentiation of both hDPSCs and hBMSCs and considerably enhance mineralisation in a controlled and concentration-dependent manner opens new perspectives for stem cell-based regenerative approaches in the clinics.
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Affiliation(s)
- Sandra Nikolic
- Orofacial Development and Regeneration, Institute of Oral Biology, Faculty of Medicine, Centre of Dental Medicine, University of Zurich, 8032 Zurich, Switzerland; (S.N.); (G.A.)
| | - Giuseppe Alastra
- Orofacial Development and Regeneration, Institute of Oral Biology, Faculty of Medicine, Centre of Dental Medicine, University of Zurich, 8032 Zurich, Switzerland; (S.N.); (G.A.)
- Department of Veterinary Medical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Felix Pultar
- Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland; (F.P.); (L.L.); (E.M.C.)
| | - Lukas Lüthy
- Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland; (F.P.); (L.L.); (E.M.C.)
| | - Bernd Stadlinger
- Clinic of Cranio-Maxillofacial and Oral Surgery, University of Zurich, 8032 Zurich, Switzerland;
| | - Erick M. Carreira
- Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland; (F.P.); (L.L.); (E.M.C.)
| | - Isaac Maximiliano Bugueno
- Orofacial Development and Regeneration, Institute of Oral Biology, Faculty of Medicine, Centre of Dental Medicine, University of Zurich, 8032 Zurich, Switzerland; (S.N.); (G.A.)
| | - Thimios A. Mitsiadis
- Orofacial Development and Regeneration, Institute of Oral Biology, Faculty of Medicine, Centre of Dental Medicine, University of Zurich, 8032 Zurich, Switzerland; (S.N.); (G.A.)
- Foundation for Research and Technology—Hellas (FORTH), University of Crete, 700 13 Heraklion, Greece
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Korkmaz Y, Pryymachuk G, Schroeter MM, Puladi B, Piekarek N, Appel S, Bloch W, Lackmann JW, Deschner J, Friebe A. The α 1- and β 1-Subunits of Nitric Oxide-Sensitive Guanylyl Cyclase in Pericytes of Healthy Human Dental Pulp. Int J Mol Sci 2024; 26:30. [PMID: 39795887 PMCID: PMC11720548 DOI: 10.3390/ijms26010030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 12/16/2024] [Accepted: 12/20/2024] [Indexed: 01/13/2025] Open
Abstract
Nitric oxide-sensitive guanylyl cyclase (NO-GC) is a heterodimeric enzyme with an α- and a β-subunit. In its active form as an α1β1-heterodimer, NO-GC produces cyclic guanosine-3',5'-monophophate (cGMP) to regulate vasodilation and proliferation of vascular smooth muscle cells (VSMCs). In contrast to VSMCs, only a few studies reported on the expression of the NO-GC α1β1-heterodimer in human pericytes. Since NO-GC is a marker for platelet-derived growth factor-β (PDGFRβ)-positive pericytes, we investigated whether NO-GC is expressed in its active α1β1-heterodimer in pericytes of healthy human dental pulp. In our previous studies, we developed and validated an antibody against the α1-subunit of human NO-GC. Here, we developed a new antibody against the β1-subunit of human NO-GC and validated it by immunoblot, mass spectrometry, and immunohistochemistry on tissue samples from humans and NO-GC knockout (GCKO) mice. Using both antibodies, we detected α1- and β1-subunits of NO-GC in pericytes of pre-capillary arterioles, capillaries, and post-capillary venules in dental pulp of decalcified and non-decalcified human molars. We concluded that NO-GC as an active α1β1-heterodimer may be involved in the regulation of vascular permeability, vascular stability, organ homeostasis, and organ regeneration in healthy human dental pulp.
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Affiliation(s)
- Yüksel Korkmaz
- Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany;
| | - Galyna Pryymachuk
- Institute of Anatomy, Brandenburg Medical School Theodor Fontane, 14770 Brandenburg an der Havel, Germany;
- Department of Anatomy I, University of Cologne, 50937 Cologne, Germany
| | - Mechthild M. Schroeter
- Center for Physiology and Pathophysiology Faculty of Medicine and University Hospital Cologne, 51109 Cologne, Germany;
| | - Behrus Puladi
- Department of Oral and Maxillofacial Surgery, University Hospital RWTH Aachen, RWTH Aachen University, 52074 Aachen, Germany;
| | - Nadin Piekarek
- Experimental Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 51109 Cologne, Germany;
| | - Sarah Appel
- Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany;
| | - Wilhelm Bloch
- Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, 50933 Cologne, Germany;
| | - Jan-Wilm Lackmann
- Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany;
| | - James Deschner
- Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany;
| | - Andreas Friebe
- Institute of Physiology, University of Würzburg, 97070 Würzburg, Germany;
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Nakazato H, Onodera S, Aida N, Furusawa M, Azuma T. Comprehensive analysis of transcription factors involved in odontoblast differentiation mechanism. Med Mol Morphol 2024; 57:253-267. [PMID: 38987402 DOI: 10.1007/s00795-024-00389-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 04/18/2024] [Indexed: 07/12/2024]
Abstract
Primary cultured odontoblasts rapidly lose their tissue-specific phenotype. To identify transcription factors (TF) that are important for the maintenance of the odontoblast phenotype, primary cultures of C57BL/6 J mouse dental mesenchymal cells (DMC) were isolated, and expression of TF and odontoblast marker genes in cells immediately after isolation and 2 days after culture were comprehensively evaluated and compared using RNA-sequencing (RNA-seq). The expression of odontoblast markers in mouse dental mesenchymal cells decreased rapidly after isolation. In addition, the expression of Hedgehog-related, Notch-related, and immediate- early gene (IEG)-related transcription factors significantly decreased. Forced expression of these genes in lentiviral vectors, together with fibroblast growth factor 4 (FGF4), fibroblast growth factor 9 (FGF9), and the Wnt pathway activator CHIR99021, significantly induced the expression of odontogenic marker genes. These results indicate, for the first time, that Notch signaling and early genes may be important for maintaining odontoblast cultures. Furthermore, simultaneous stimulation of FGF, Wnt, Hedgehog, Notch pathways, and IEG transcription factors cooperatively promoted the maintenance of the odontoblast phenotype. These results suggest that the Hedgehog and Notch signaling pathways may play an important role in maintaining odontoblast phenotypes, in addition to FGF and Wnt signaling.
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Affiliation(s)
- Haruka Nakazato
- Department of Endodontics, Tokyo Dental College, 2-9-18 Kanda-Misaki-Chou, Chiyoda, Tokyo, 101-0061, Japan
| | - Shoko Onodera
- Department of Biochemistry, Tokyo Dental College, 2-9-18 Kanda-Misaki-Chou, Chiyoda, Tokyo, 101-0061, Japan
| | - Natsuko Aida
- Department of Biochemistry, Tokyo Dental College, 2-9-18 Kanda-Misaki-Chou, Chiyoda, Tokyo, 101-0061, Japan
| | - Masahiro Furusawa
- Department of Endodontics, Tokyo Dental College, 2-9-18 Kanda-Misaki-Chou, Chiyoda, Tokyo, 101-0061, Japan
| | - Toshifumi Azuma
- Department of Biochemistry, Tokyo Dental College, 2-9-18 Kanda-Misaki-Chou, Chiyoda, Tokyo, 101-0061, Japan.
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Parchami K, Dastorani M, Barati M. What is the impact of Endodontic Irrigant Solutions on the Viability of Stem Cells from Apical Papilla in an in-vitro setting: A Systematic Review. Saudi Dent J 2024; 36:1170-1178. [PMID: 39286587 PMCID: PMC11402017 DOI: 10.1016/j.sdentj.2024.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 07/01/2024] [Accepted: 07/04/2024] [Indexed: 09/19/2024] Open
Abstract
Background The success of regenerative endodontic procedures (REPs) is significantly influenced by the choice of endodontic irrigant solution. However, the impact of these solutions on the viability of stem cells from the apical papilla (SCAP), a critical component of the REP, remains a subject of ongoing debate. Objective This study aimed to investigate the effects of various endodontic irrigant solutions on the viability of stem cells from the apical papilla in an in vitro setting. Methods A systematic literature search was conducted using databases such as PubMed/Medline, Scopus, the Cochrane Library, Web of Science, Embase, gray literature, and reference lists up to August 2023. The search was limited to in vitro studies investigating the impact of endodontic irrigant solutions on SCAP viability. The risk of bias in these studies was evaluated using the Joanna Briggs Institute's checklist. Results Of the 131 articles retrieved, 14 were selected for review. The effects of eighteen different root canal irrigants, such as ethylenediaminetetraacetic acid, sodium hypochlorite, chlorhexidine, and citric acid, on the viability of SCAPs were evaluated. The risk-of-bias analysis showed a high risk in sample randomization and size justification but a low risk in other areas. Discussion The effects of endodontic irrigant solutions on the viability of SCAPs are concentration dependent. Concentrations higher than 1.5% sodium hypochlorite, 2 % chlorhexidine, 10 % citric acid, and 2.5 % EDTA significantly reduced cell viability. However, additional research is necessary to determine the effect of these irrigants on tissue regeneration.
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Affiliation(s)
- Kiarash Parchami
- Infectious Diseases Research Center, AJA University of Medical Sciences, Tehran, Iran
| | - Mehdi Dastorani
- Trauma and Surgery Research Center, Aja University of Medical Sciences, Tehran, Iran
- Department of Endodontics, School of Dentistry, AJA University of Medical Sciences, Tehran, Iran
| | - Mohammad Barati
- Infectious Diseases Research Center, AJA University of Medical Sciences, Tehran, Iran
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Omerkić Dautović D, Hodžić B, Omerkić S. Application of Stem Cells in Dentistry: A Review Article. IFMBE PROCEEDINGS 2024:726-745. [DOI: 10.1007/978-3-031-49068-2_75] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Pan H, Yang Y, Xu H, Jin A, Huang X, Gao X, Sun S, Liu Y, Liu J, Lu T, Wang X, Zhu Y, Jiang L. The odontoblastic differentiation of dental mesenchymal stem cells: molecular regulation mechanism and related genetic syndromes. Front Cell Dev Biol 2023; 11:1174579. [PMID: 37818127 PMCID: PMC10561098 DOI: 10.3389/fcell.2023.1174579] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Accepted: 08/24/2023] [Indexed: 10/12/2023] Open
Abstract
Dental mesenchymal stem cells (DMSCs) are multipotent progenitor cells that can differentiate into multiple lineages including odontoblasts, osteoblasts, chondrocytes, neural cells, myocytes, cardiomyocytes, adipocytes, endothelial cells, melanocytes, and hepatocytes. Odontoblastic differentiation of DMSCs is pivotal in dentinogenesis, a delicate and dynamic process regulated at the molecular level by signaling pathways, transcription factors, and posttranscriptional and epigenetic regulation. Mutations or dysregulation of related genes may contribute to genetic diseases with dentin defects caused by impaired odontoblastic differentiation, including tricho-dento-osseous (TDO) syndrome, X-linked hypophosphatemic rickets (XLH), Raine syndrome (RS), hypophosphatasia (HPP), Schimke immuno-osseous dysplasia (SIOD), and Elsahy-Waters syndrome (EWS). Herein, recent progress in the molecular regulation of the odontoblastic differentiation of DMSCs is summarized. In addition, genetic syndromes associated with disorders of odontoblastic differentiation of DMSCs are discussed. An improved understanding of the molecular regulation and related genetic syndromes may help clinicians better understand the etiology and pathogenesis of dentin lesions in systematic diseases and identify novel treatment targets.
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Affiliation(s)
- Houwen Pan
- Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
- Shanghai Research Institute of Stomatology, Shanghai, China
| | - Yiling Yang
- Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
- Shanghai Research Institute of Stomatology, Shanghai, China
| | - Hongyuan Xu
- Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
- Shanghai Research Institute of Stomatology, Shanghai, China
| | - Anting Jin
- Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
- Shanghai Research Institute of Stomatology, Shanghai, China
| | - Xiangru Huang
- Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
- Shanghai Research Institute of Stomatology, Shanghai, China
| | - Xin Gao
- Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
- Shanghai Research Institute of Stomatology, Shanghai, China
| | - Siyuan Sun
- Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
- Shanghai Research Institute of Stomatology, Shanghai, China
| | - Yuanqi Liu
- Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
- Shanghai Research Institute of Stomatology, Shanghai, China
| | - Jingyi Liu
- Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
- Shanghai Research Institute of Stomatology, Shanghai, China
| | - Tingwei Lu
- Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
- Shanghai Research Institute of Stomatology, Shanghai, China
| | - Xinyu Wang
- Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
- Shanghai Research Institute of Stomatology, Shanghai, China
| | - Yanfei Zhu
- Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
- Shanghai Research Institute of Stomatology, Shanghai, China
| | - Lingyong Jiang
- Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
- Shanghai Research Institute of Stomatology, Shanghai, China
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Yoshida K, Suzuki S, Yuan H, Sato A, Hirata-Tsuchiya S, Saito M, Yamada S, Shiba H. Public RNA-seq data-based identification and functional analyses reveal that MXRA5 retains proliferative and migratory abilities of dental pulp stem cells. Sci Rep 2023; 13:15574. [PMID: 37730838 PMCID: PMC10511426 DOI: 10.1038/s41598-023-42684-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Accepted: 09/13/2023] [Indexed: 09/22/2023] Open
Abstract
Dental pulp stem cells (DPSC) usually remain quiescent in the dental pulp tissue; however, once the dental pulp tissue is injured, DPSCs potently proliferate and migrate into the injury microenvironment and contribute to immuno-modulation and tissue repair. However, the key molecules that physiologically support the potent proliferation and migration of DPSCs have not been revealed. In this study, we searched publicly available transcriptome raw data sets, which contain comparable (i.e., equivalently cultured) DPSC and mesenchymal stem cell data. Three data sets were extracted from the Gene Expression Omnibus database and then processed and analyzed. MXRA5 was identified as the predominant DPSC-enriched gene associated with the extracellular matrix. MXRA5 is detected in human dental pulp tissues. Loss of MXRA5 drastically decreases the proliferation and migration of DSPCs, concomitantly with reduced expression of the genes associated with the cell cycle and microtubules. In addition to the known full-length isoform of MXRA5, a novel splice variant of MXRA5 was cloned in DPSCs. Recombinant MXRA5 coded by the novel splice variant potently induced the haptotaxis migration of DPSCs, which was inhibited by microtubule inhibitors. Collectively, MXRA5 is a key extracellular matrix protein in dental pulp tissue for maintaining the proliferation and migration of DPSCs.
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Affiliation(s)
- Kazuma Yoshida
- Department of Biological Endodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan
| | - Shigeki Suzuki
- Department of Biological Endodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.
- Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, 980-8575, Japan.
| | - Hang Yuan
- Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, 980-8575, Japan
| | - Akiko Sato
- Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, 980-8575, Japan
| | - Shizu Hirata-Tsuchiya
- Department of Biological Endodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan
| | - Masahiro Saito
- Department of Restorative Dentistry, Tohoku University Graduate School of Dentistry, Sendai, 980-8575, Japan
| | - Satoru Yamada
- Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, 980-8575, Japan
| | - Hideki Shiba
- Department of Biological Endodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan
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Siddiqui Z, Acevedo-Jake AM, Griffith A, Kadincesme N, Dabek K, Hindi D, Kim KK, Kobayashi Y, Shimizu E, Kumar V. Cells and material-based strategies for regenerative endodontics. Bioact Mater 2022; 14:234-249. [PMID: 35310358 PMCID: PMC8897646 DOI: 10.1016/j.bioactmat.2021.11.015] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 10/29/2021] [Accepted: 11/09/2021] [Indexed: 12/21/2022] Open
Abstract
The carious process leads to inflammation of pulp tissue. Current care options include root canal treatment or apexification. These procedures, however, result in the loss of tooth vitality, sensitivity, and healing. Pulp capping and dental pulp regeneration are continually evolving techniques to regenerate pulp tissue, avoiding necrosis and loss of vitality. Many studies have successfully employed stem/progenitor cell populations, revascularization approaches, scaffolds or material-based strategies for pulp regeneration. Here we outline advantages and disadvantages of different methods and techniques which are currently being used in the field of regenerative endodontics. We also summarize recent findings on efficacious peptide-based materials which target the dental niche. .
Affiliation(s)
- Zain Siddiqui
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Amanda M. Acevedo-Jake
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Alexandra Griffith
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Nurten Kadincesme
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Kinga Dabek
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Dana Hindi
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Ka Kyung Kim
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Yoshifumi Kobayashi
- Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ, 07103, USA
| | - Emi Shimizu
- Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ, 07103, USA
- Department of Endodontics, Rutgers School of Dental Medicine, Newark, NJ, 07103, USA
| | - Vivek Kumar
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
- Department of Endodontics, Rutgers School of Dental Medicine, Newark, NJ, 07103, USA
- Department of Chemicals and Materials Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
- Department of Biology, New Jersey Institute of Technology, Newark, NJ, 07102, USA
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Nel S, Durandt C, Murdoch C, Pepper MS. Determinants of Dental Pulp Stem Cell Heterogeneity. J Endod 2022; 48:1232-1240. [PMID: 35809811 DOI: 10.1016/j.joen.2022.06.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 06/27/2022] [Accepted: 06/28/2022] [Indexed: 11/17/2022]
Abstract
INTRODUCTION The aim of this review is to provide a narrative review on the determinants of dental pulp stem cell (DPSC) heterogeneity that may affect the regenerative properties of these cells. METHODS PubMed, Scopus and Medline (Ovid) literature searches were done on human dental pulp stem cell (hDPSC) heterogeneity. The focus was on human dental pulp stem cells (hDPSCs) with a primary focus on DPSC heterogeneity. RESULTS DPSCs display significant heterogeneity as illustrated by the various subpopulations reported, including differences in proliferation and differentiation capabilities and the impact of various intrinsic and extrinsic factors. CONCLUSIONS The lack of consistent and reliable results in the clinical setting may be due to the heterogeneous nature of DPSC populations. Standardization in isolation techniques and in criteria to characterize DPSCs should lead to less variability in results reported and improve comparison of findings between studies. Single-cell RNA sequencing holds promise in elucidating DPSC heterogeneity and may contribute to the establishment of standardized techniques.
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Affiliation(s)
- Sulette Nel
- Department of Oral Pathology and Oral Biology, School of Dentistry, Faculty of Health Sciences, University of Pretoria, South Africa.
| | - Chrisna Durandt
- Institute for Cellular and Molecular Medicine (ICMM), Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, South Africa
| | - Candice Murdoch
- Institute for Cellular and Molecular Medicine (ICMM), Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, South Africa
| | - Michael S Pepper
- Institute for Cellular and Molecular Medicine (ICMM), Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, South Africa
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Komada T, Mitomo K, Ikarashi T, Shimono M, Jung HS, Muramatsu T. Periodontal Ligament Cells Are Involved in the Formation of Intracanal Cementum-Like Tissue After Regenerative Endodontic Procedures: A Mouse in situ Model. FRONTIERS IN DENTAL MEDICINE 2022. [DOI: 10.3389/fdmed.2022.864406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Regenerative endodontic cell-homing procedures are frequently performed on injured immature teeth diagnosed with pulp necrosis and/or apical periodontitis. The representative histological finding after those procedures is cementum-like tissues filling in the root canal but details of the healing process remain unknown. We investigated that healing process histologically using a mouse in situ model. Regenerative endodontic procedures were experimentally performed on noninfected maxillary first molars of 6-week-old male C57BL/6 mice, after which the healing process was investigated using histology and immunohistochemistry. Immediately after the regenerative endodontic cell-homing procedures, blood clots were seen in the root canals that disappeared over time. On day 7, the blot clot in the root canal was replaced by granulation tissue. From day 14 onward, cementum-like tissues were filled in the root canals, while the amount of fibrous tissue was reduced. Immunohistochemically, positive reactions for periostin were seen in the fibrous tissue in the root canal, the apex, and periodontal ligament cells. On the other hand, positive reactions for nestin were not detected in the root canal. CD31-positive cells with a luminal structure were also observed in the fibrous tissue around the apex and around the newly formed cementum-like tissues in the root canal. Thus, in this study, we have established an in situ mouse model of regenerative endodontic procedures. The results of this study suggest that periodontal ligament cells and vascular endothelial cells grow into the root canals from the apex, replace the blood clots, and participate in the formation of cementum-like tissues with angiogenesis during the healing process of regenerative endodontic procedures.
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11
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Fonticoli L, Della Rocca Y, Rajan TS, Murmura G, Trubiani O, Oliva S, Pizzicannella J, Marconi GD, Diomede F. A Narrative Review: Gingival Stem Cells as a Limitless Reservoir for Regenerative Medicine. Int J Mol Sci 2022; 23:ijms23084135. [PMID: 35456951 PMCID: PMC9024914 DOI: 10.3390/ijms23084135] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 04/05/2022] [Accepted: 04/07/2022] [Indexed: 11/16/2022] Open
Abstract
The gingival tissue can be collected in an easy way and represent an accessible source to isolate gingival-derived mesenchymal stem cells (GMSCs). GMSCs are a subpopulation of dental-derived mesenchymal stem cells that show the mesenchymal stem cells (MSCs) features, such as differentiation abilities and immunomodulatory properties. Dental-derived stem cells are also expandable in vitro with genomic stability and the possibility to maintain the stemness properties over a prolonged period of passages. Moreover, several preclinical studies have documented that the extracellular vesicles (EVs) released from GMSCs possess similar biological functions and therapeutic effects. The EVs may represent a promising tool in the cell-free regenerative therapy approach. The present review paper summarized the GMSCs, their multi-lineage differentiation capacities, immunomodulatory features, and the potential use in the treatment of several diseases in order to stimulate tissue regeneration. GMSCs should be considered a good stem cell source for potential applications in tissue engineering and regenerative dentistry.
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Affiliation(s)
- Luigia Fonticoli
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
| | - Ylenia Della Rocca
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
| | | | - Giovanna Murmura
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
| | - Oriana Trubiani
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
| | - Stefano Oliva
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
| | | | - Guya Diletta Marconi
- Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
| | - Francesca Diomede
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
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12
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Shaikh MS, Shahzad Z, Tash EA, Janjua OS, Khan MI, Zafar MS. Human Umbilical Cord Mesenchymal Stem Cells: Current Literature and Role in Periodontal Regeneration. Cells 2022; 11:cells11071168. [PMID: 35406732 PMCID: PMC8997495 DOI: 10.3390/cells11071168] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/27/2022] [Accepted: 03/29/2022] [Indexed: 12/21/2022] Open
Abstract
Periodontal disease can cause irreversible damage to tooth-supporting tissues such as the root cementum, periodontal ligament, and alveolar bone, eventually leading to tooth loss. While standard periodontal treatments are usually helpful in reducing disease progression, they cannot repair or replace lost periodontal tissue. Periodontal regeneration has been demonstrated to be beneficial in treating intraosseous and furcation defects to varied degrees. Cell-based treatment for periodontal regeneration will become more efficient and predictable as tissue engineering and progenitor cell biology advance, surpassing the limitations of present therapeutic techniques. Stem cells are undifferentiated cells with the ability to self-renew and differentiate into several cell types when stimulated. Mesenchymal stem cells (MSCs) have been tested for periodontal regeneration in vitro and in humans, with promising results. Human umbilical cord mesenchymal stem cells (UC-MSCs) possess a great regenerative and therapeutic potential. Their added benefits comprise ease of collection, endless source of stem cells, less immunorejection, and affordability. Further, their collection does not include the concerns associated with human embryonic stem cells. The purpose of this review is to address the most recent findings about periodontal regenerative mechanisms, different stem cells accessible for periodontal regeneration, and UC-MSCs and their involvement in periodontal regeneration.
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Affiliation(s)
- Muhammad Saad Shaikh
- Department of Oral Biology, Sindh Institute of Oral Health Sciences, Jinnah Sindh Medical University, Karachi 75510, Pakistan;
| | - Zara Shahzad
- Lahore Medical and Dental College, University of Health Sciences, Lahore 53400, Pakistan;
| | - Esraa Abdulgader Tash
- Department of Oral and Clinical Basic Science, College of Dentistry, Taibah University, Al Madinah Al Munawarah 41311, Saudi Arabia;
| | - Omer Sefvan Janjua
- Department of Maxillofacial Surgery, PMC Dental Institute, Faisalabad Medical University, Faisalabad 38000, Pakistan;
| | | | - Muhammad Sohail Zafar
- Department of Restorative Dentistry, College of Dentistry, Taibah University, Al Madinah Al Munawarah 41311, Saudi Arabia
- Department of Dental Materials, Islamic International Dental College, Riphah International University, Islamabad 44000, Pakistan
- Correspondence: ; Tel.: +966-507544691
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Koh B, Ab Rahman FH, Matlan NA, Rajan M, Musta'ain AY, Mohd Jeffry Lee MR, Ramli R, Mohd Yunus SS, Binti Hj Idrus R, Yazid MD. Potential role of dental pulp stem cells conditioned medium for odontoblastic differentiation. Biol Res 2022; 55:11. [PMID: 35246266 PMCID: PMC8895822 DOI: 10.1186/s40659-022-00380-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Accepted: 02/17/2022] [Indexed: 12/03/2022] Open
Abstract
Background Functional bioengineered tooth regeneration using autologous or allogeneic alternative differentiated cells sources are thought to have a great potential in replacing conventional dentures. This study investigated the potential of dental pulp stem cells (DPSCs) conditioned medium for odontoblastic differentiation of Wharton’s jelly mesenchymal stem cells (WJMSCs). The DPSCs derived from healthy adult permanent first molars were cultured at high confluence prior to conditioned medium collection. The WJMSCs were cultured in six different treatments, with varying ratios of culture media to DPSCs-conditioned medium. MTT assay was used to measure the rate of proliferation of WJMSCs, while immunocytochemistry staining was utilised to detect the expression of dental matrix protein 1 (DMP-1). The deposited calcium was detected and analysed via Alizarin-Red Staining (ARS). Results It was found that the proliferation of WJMSCs cultured under the mixture of complete medium and DPSCs conditioned medium showed significantly lower than the control; presumably the cells started to exit proliferative state prior differentiation. In 14 days of induction, the cells in all treatments showed osteoblastic-like morphology, calcium compound deposits were observed at day 7, 10 and 14 of differentiation suggested that DPSCs conditioned medium could lead to osteoblastic/odontoblastic differentiation. However, the DMP-1 protein can be seen only expressed minimally at day 14 of conditioned medium induction. Conclusions In conclusion, DPSCs conditioned medium appeared as a potential odontoblastic induction approach for WJMSCs. To further investigate the stimulatory effects by DPSCs conditioned medium, specific signalling pathway need to be elucidated to enhance the differentiation efficiency.
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Affiliation(s)
- Benson Koh
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Cheras, 56000, Kuala Lumpur, Malaysia
| | - Farynna Hana Ab Rahman
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Cheras, 56000, Kuala Lumpur, Malaysia
| | - Najwa Amira Matlan
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Cheras, 56000, Kuala Lumpur, Malaysia
| | - Manissha Rajan
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Cheras, 56000, Kuala Lumpur, Malaysia
| | - Aimi Yasmin Musta'ain
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Cheras, 56000, Kuala Lumpur, Malaysia
| | - Mohamad Ridhwan Mohd Jeffry Lee
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Cheras, 56000, Kuala Lumpur, Malaysia
| | - Roszalina Ramli
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia
| | - Siti Salmiah Mohd Yunus
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia
| | - Ruszymah Binti Hj Idrus
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Cheras, 56000, Kuala Lumpur, Malaysia
| | - Muhammad Dain Yazid
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Cheras, 56000, Kuala Lumpur, Malaysia.
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14
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Rusu MC, Vrapciu AD, Nicolescu MI, Stoenescu MD, Jianu AM, Lighezan R, Oancea R, Mănoiu VS, Hostiuc S. Extruded Nucleoli of Human Dental Pulp Cells. Medicina (B Aires) 2022; 58:medicina58020260. [PMID: 35208583 PMCID: PMC8876639 DOI: 10.3390/medicina58020260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 02/04/2022] [Accepted: 02/06/2022] [Indexed: 11/22/2022] Open
Abstract
Background and Objectives: The dental pulp stem cells are highly proliferative and can differentiate into various cell types, including endothelial cells. We aimed to evaluate the ultrastructural characteristics of the human dental pulp cells of the permanent frontal teeth. Materials and Methods: Human adult bioptic dental pulp was collected from n = 10 healthy frontal teeth of five adult patients, prior to prosthetic treatments for aesthetic purposes. Tissues were examined under transmission electron microscopy. Results: We identified cells with a peculiar trait: giant nucleoli resembling intranuclear endoplasmic reticulum, which mimicked extrusion towards the cytoplasm. These were either partly embedded within the nuclei, the case in which their adnuclear side was coated by marginal heterochromatin and the abnuclear side was coated by a thin rim of ribosomes, or were apparently isolated from the nuclei, while still being covered by ribosomes. Conclusions: Similar electron microscopy features were previously reported in the human endometrium, as nucleolar channel system; or R-Rings induced by Nopp140. To our knowledge, this is the first report of extruded nucleolar structure in the dental pulp. Moreover, the aspect of giant extruded nucleoli was not previously reported in any human cell type, although similar evidence was gathered in other species as well as in plants.
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Affiliation(s)
- Mugurel Constantin Rusu
- Division of Anatomy, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.C.R.); (A.D.V.)
| | - Alexandra Diana Vrapciu
- Division of Anatomy, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.C.R.); (A.D.V.)
| | - Mihnea Ioan Nicolescu
- Division of Histology, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Laboratory of Radiobiology, “Victor Babeș” National Institute of Pathology, 050096 Bucharest, Romania
- Correspondence: (M.I.N.); (A.M.J.)
| | - Mihai Dragomir Stoenescu
- Research Department, “Dr. Carol Davila” Central Military Emergency Hospital, 010825 Bucharest, Romania;
| | - Adelina Maria Jianu
- Department of Anatomy, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, 300041 Timişoara, Romania
- Correspondence: (M.I.N.); (A.M.J.)
| | - Rodica Lighezan
- Department of Histology, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, 300041 Timişoara, Romania;
| | - Roxana Oancea
- Department of Preventive and Community Dentistry, Faculty of Dental Medicine, “Victor Babeş” University of Medicine and Pharmacy, 300041 Timişoara, Romania;
| | - Vasile Sorin Mănoiu
- Department of Cellular and Molecular Biology, National Institute of Research and Development for Biological Sciences, 060031 Bucharest, Romania;
| | - Sorin Hostiuc
- Division of Legal Medicine, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania;
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15
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Rong W, Rome C, Yao S. Increased Expression of miR-7a-5p and miR-592 during Expansion of Rat Dental Pulp Stem Cells and Their Implication in Osteogenic Differentiation. Cells Tissues Organs 2022; 211:41-56. [PMID: 34530424 PMCID: PMC8766878 DOI: 10.1159/000519600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Accepted: 09/12/2021] [Indexed: 01/03/2023] Open
Abstract
Dental pulp stem cells (DPSCs) possess strong osteogenic differentiation potential and are promising cell sources in regenerative medicine. However, such differentiation capacity progressively declines during their in vitro expansion. MicroRNAs (miRNAs) play important roles in modulating stem cell differentiation. This study aimed (1) to determine if miR-7a-5p and miR-592 are involved in maintaining and regulating osteogenic differentiation of DPSCs, and (2) to explore their potential regulatory pathways. We found that the expression of miR-7a-5p and miR-592 was significantly upregulated during the expansion of rat DPSCs (rDPSCs). Overexpression of these miRNAs inhibited the osteogenic/odontogenic differentiation of rDPSCs, as evidenced by calcium deposition and osteogenic/odontogenic gene expression. RT-qPCR determined that miR-592 could downregulate heat shock protein B8, whose expression is reduced during the expansion of rDPSCs. Furthermore, RNA-seq and bioinformatics analysis identified significant signaling pathways of miR-7a-5p and miR-592 in regulating osteogenic differentiation, including TNF, MAPK, and PI3K-Akt pathways. We conclude that upregulating miR-7a-5p and miR-592 suppresses the osteogenic differentiation of rDPSCs during their in vitro expansion, likely via TNF, MAPK, and PI3K-Akt pathways. The results may shed light on application of miR-7a-5p and miR-592 for maintaining osteo-differentiation potential in stem cells for bone regeneration and bone-related disease treatment.
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Affiliation(s)
| | | | - Shaomian Yao
- Corresponding author: Shaomian Yao, Ph.D., Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA, Tel: +1-225-578-9889, Fax: +1-225-578-9895,
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16
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Al Madhoun A, Sindhu S, Haddad D, Atari M, Ahmad R, Al-Mulla F. Dental Pulp Stem Cells Derived From Adult Human Third Molar Tooth: A Brief Review. Front Cell Dev Biol 2021; 9:717624. [PMID: 34712658 PMCID: PMC8545885 DOI: 10.3389/fcell.2021.717624] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 09/15/2021] [Indexed: 12/13/2022] Open
Abstract
The fields of regenerative medicine and stem cell-based tissue engineering have the potential of treating numerous tissue and organ defects. The use of adult stem cells is of particular interest when it comes to dynamic applications in translational medicine. Recently, dental pulp stem cells (DPSCs) have been traced in third molars of adult humans. DPSCs have been isolated and characterized by several groups. DPSCs have promising characteristics including self-renewal capacity, rapid proliferation, colony formation, multi-lineage differentiation, and pluripotent gene expression profile. Nevertheless, genotypic, and phenotypic heterogeneities have been reported for DPSCs subpopulations which may influence their therapeutic potentials. The underlying causes of DPSCs' heterogeneity remain poorly understood; however, their heterogeneity emerges as a consequence of an interplay between intrinsic and extrinsic cellular factors. The main objective of the manuscript is to review the current literature related to the human DPSCs derived from the third molar, with a focus on their physiological properties, isolation procedures, culture conditions, self-renewal, proliferation, lineage differentiation capacities and their prospective advances use in pre-clinical and clinical applications.
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Affiliation(s)
- Ashraf Al Madhoun
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait
- Department of Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman, Kuwait
| | - Sardar Sindhu
- Department of Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman, Kuwait
- Department of Immunology and Microbiology, Dasman Diabetes Institute, Dasman, Kuwait
| | - Dania Haddad
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait
| | - Maher Atari
- Biointelligence Technology Systems S.L., Barcelona, Spain
| | - Rasheed Ahmad
- Department of Immunology and Microbiology, Dasman Diabetes Institute, Dasman, Kuwait
| | - Fahd Al-Mulla
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait
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17
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Effect of Different Root Canal Irrigant Solutions on the Release of Dentin-Growth Factors: A Systematic Review and Meta-Analysis. MATERIALS 2021; 14:ma14195829. [PMID: 34640224 PMCID: PMC8510123 DOI: 10.3390/ma14195829] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 09/22/2021] [Accepted: 09/29/2021] [Indexed: 01/07/2023]
Abstract
Irrigant solutions are used to promote dentin-growth factors (GF) release for regenerative endodontics. This review aimed to evaluate the reports comparing the release of GFs using different root canal irrigant solutions. Eligible studies compared the in vitro GF release in human teeth after the use of at least two distinct solutions. A search was conducted on Pubmed, Scopus, Web of Science, and Lilacs on 11 August 2021. Risk of bias was assessed using SciRAP. Study characteristics and quantitative data were extracted, and meta-analyses were performed for the mean difference (95% confidence interval) of the release of transforming growth factors Beta 1 (TGF-β1) by EDTA compared to other irrigants. Of sixteen eligible studies, eight were included in quantitative analysis. ELISA assays showed higher TGF-β1 release from 10% EDTA compared to 10% citric acid (p < 0.00001). Immunogold assays showed higher levels of TGF-β1 for 17% EDTA (p < 0.00001) compared to 10% citric acid. GRADE identified a low to very low certainty of evidence. These results point to an increased release of TGF-β1 in dentin treated with EDTA. The high heterogeneity and very low certainty of the evidence demand further studies before EDTA indication as a better irrigant for regenerative endodontics. Registration: CRD42020160871 (PROSPERO).
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Pagella P, de Vargas Roditi L, Stadlinger B, Moor AE, Mitsiadis TA. Notch signaling in the dynamics of perivascular stem cells and their niches. Stem Cells Transl Med 2021; 10:1433-1445. [PMID: 34227747 PMCID: PMC8459638 DOI: 10.1002/sctm.21-0086] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 04/20/2021] [Accepted: 05/02/2021] [Indexed: 12/11/2022] Open
Abstract
The Notch signaling pathway is a fundamental regulator of cell fate determination in homeostasis and regeneration. In this work, we aimed to determine how Notch signaling mediates the interactions between perivascular stem cells and their niches in human dental mesenchymal tissues, both in homeostatic and regenerative conditions. By single cell RNA sequencing analysis, we showed that perivascular cells across the dental pulp and periodontal human tissues all express NOTCH3, and that these cells are important for the response to traumatic injuries in vivo in a transgenic mouse model. We further showed that the behavior of perivascular NOTCH3‐expressing stem cells could be modulated by cellular and molecular cues deriving from their microenvironments. Taken together, the present studies, reinforced by single‐cell analysis, reveal the pivotal importance of Notch signaling in the crosstalk between perivascular stem cells and their niches in tissue homeostasis and regeneration.
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Affiliation(s)
- Pierfrancesco Pagella
- Orofacial Development and Regeneration, Institute of Oral Biology, Center of Dental Medicine, University of Zurich, Zurich, Switzerland
| | - Laura de Vargas Roditi
- Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.,Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland
| | - Bernd Stadlinger
- Clinic of Cranio-Maxillofacial and Oral Surgery, Center of Dental Medicine, University of Zurich, Zurich, Switzerland
| | - Andreas E Moor
- Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.,Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland
| | - Thimios A Mitsiadis
- Orofacial Development and Regeneration, Institute of Oral Biology, Center of Dental Medicine, University of Zurich, Zurich, Switzerland
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Ehlinger C, Mathieu E, Rabineau M, Ball V, Lavalle P, Haikel Y, Vautier D, Kocgozlu L. Insensitivity of dental pulp stem cells migration to substrate stiffness. Biomaterials 2021; 275:120969. [PMID: 34157563 DOI: 10.1016/j.biomaterials.2021.120969] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/26/2021] [Accepted: 06/09/2021] [Indexed: 12/16/2022]
Abstract
Dental pulp stem cells (DPSCs) are a promising cell source for regeneration of dental pulp. Migration is a key event but influence of the microenvironment rigidity (5 kPa at the center of dental pulp to 20 GPa for the dentin) is largely unknown. Mechanical signals are transmitted from the extracellular matrix to the cytoskeleton, to the nuclei, and to the chromatin, potentially regulating gene expression. To identify the microenvironmental influence on migration, we analyzed motility on PDMS substrates with stiffness increasing from 1.5 kPa up to 2.5 MPa. We found that migration speed slightly increases as substrate stiffness decreases in correlation with decreasing focal adhesion size. Motility is relatively insensitive to substrate stiffness, even on a bi-rigidity PDMS substrate where DPSCs migrate without preferential direction. Migration is independent of both myosin II activity and YAP translocation after myosin II inhibition. Additionally, inhibition of Arp2/3 complex leads to significant speed decrease for all rigidities, suggesting contribution of the lamellipodia in the migration. Interestingly, the chromatin architecture remains stable after a 7-days exposure on the PDMS substrates for all rigidity. To design scaffold mimicking dental pulp environment, similar DPSCs migration for all rigidity, leaves field open to choose this mechanical parameter.
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Affiliation(s)
- Claire Ehlinger
- Inserm UMR-S1121, Centre de Recherche en Biomédecine de Strasbourg (CRBS), 1 rue Eugène Boeckel, 67084, Strasbourg, France; Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Sainte Elisabeth, 67000, Strasbourg, France; Fédération de Médecine Translationnelle, Strasbourg, France
| | - Eric Mathieu
- Inserm UMR-S1121, Centre de Recherche en Biomédecine de Strasbourg (CRBS), 1 rue Eugène Boeckel, 67084, Strasbourg, France; Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Sainte Elisabeth, 67000, Strasbourg, France; Fédération de Médecine Translationnelle, Strasbourg, France
| | - Morgane Rabineau
- Inserm UMR-S1121, Centre de Recherche en Biomédecine de Strasbourg (CRBS), 1 rue Eugène Boeckel, 67084, Strasbourg, France; Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Sainte Elisabeth, 67000, Strasbourg, France; Fédération de Médecine Translationnelle, Strasbourg, France
| | - Vincent Ball
- Inserm UMR-S1121, Centre de Recherche en Biomédecine de Strasbourg (CRBS), 1 rue Eugène Boeckel, 67084, Strasbourg, France; Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Sainte Elisabeth, 67000, Strasbourg, France; Fédération de Médecine Translationnelle, Strasbourg, France
| | - Philippe Lavalle
- Inserm UMR-S1121, Centre de Recherche en Biomédecine de Strasbourg (CRBS), 1 rue Eugène Boeckel, 67084, Strasbourg, France; Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Sainte Elisabeth, 67000, Strasbourg, France; Fédération de Médecine Translationnelle, Strasbourg, France
| | - Youssef Haikel
- Inserm UMR-S1121, Centre de Recherche en Biomédecine de Strasbourg (CRBS), 1 rue Eugène Boeckel, 67084, Strasbourg, France; Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Sainte Elisabeth, 67000, Strasbourg, France; Fédération de Médecine Translationnelle, Strasbourg, France
| | - Dominique Vautier
- Inserm UMR-S1121, Centre de Recherche en Biomédecine de Strasbourg (CRBS), 1 rue Eugène Boeckel, 67084, Strasbourg, France; Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Sainte Elisabeth, 67000, Strasbourg, France; Fédération de Médecine Translationnelle, Strasbourg, France.
| | - Leyla Kocgozlu
- Inserm UMR-S1121, Centre de Recherche en Biomédecine de Strasbourg (CRBS), 1 rue Eugène Boeckel, 67084, Strasbourg, France; Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Sainte Elisabeth, 67000, Strasbourg, France; Fédération de Médecine Translationnelle, Strasbourg, France.
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Olaru M, Sachelarie L, Calin G. Hard Dental Tissues Regeneration-Approaches and Challenges. MATERIALS 2021; 14:ma14102558. [PMID: 34069265 PMCID: PMC8156070 DOI: 10.3390/ma14102558] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/10/2021] [Accepted: 05/13/2021] [Indexed: 12/13/2022]
Abstract
With the development of the modern concept of tissue engineering approach and the discovery of the potential of stem cells in dentistry, the regeneration of hard dental tissues has become a reality and a priority of modern dentistry. The present review reports the recent advances on stem-cell based regeneration strategies for hard dental tissues and analyze the feasibility of stem cells and of growth factors in scaffolds-based or scaffold-free approaches in inducing the regeneration of either the whole tooth or only of its component structures.
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Affiliation(s)
- Mihaela Olaru
- “Petru Poni” Institute of Macromolecular Chemistry, 41 A Grigore Ghica Voda Alley, 700487 Iasi, Romania;
| | - Liliana Sachelarie
- Faculty of Medical Dentistry, “Apollonia” University of Iasi, 2 Muzicii Str., 700399 Iasi, Romania;
- Correspondence:
| | - Gabriela Calin
- Faculty of Medical Dentistry, “Apollonia” University of Iasi, 2 Muzicii Str., 700399 Iasi, Romania;
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21
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Ramos-Rodriguez DH, MacNeil S, Claeyssens F, Asencio IO. The Use of Microfabrication Techniques for the Design and Manufacture of Artificial Stem Cell Microenvironments for Tissue Regeneration. Bioengineering (Basel) 2021; 8:50. [PMID: 33922428 PMCID: PMC8146165 DOI: 10.3390/bioengineering8050050] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 04/19/2021] [Accepted: 04/21/2021] [Indexed: 12/13/2022] Open
Abstract
The recapitulation of the stem cell microenvironment is an emerging area of research that has grown significantly in the last 10 to 15 years. Being able to understand the underlying mechanisms that relate stem cell behavior to the physical environment in which stem cells reside is currently a challenge that many groups are trying to unravel. Several approaches have attempted to mimic the biological components that constitute the native stem cell niche, however, this is a very intricate environment and, although promising advances have been made recently, it becomes clear that new strategies need to be explored to ensure a better understanding of the stem cell niche behavior. The second strand in stem cell niche research focuses on the use of manufacturing techniques to build simple but functional models; these models aim to mimic the physical features of the niche environment which have also been demonstrated to play a big role in directing cell responses. This second strand has involved a more engineering approach in which a wide set of microfabrication techniques have been explored in detail. This review aims to summarize the use of these microfabrication techniques and how they have approached the challenge of mimicking the native stem cell niche.
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Affiliation(s)
- David H. Ramos-Rodriguez
- Bioengineering and Health Technologies Group, The School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK;
- Biomaterials and Tissue Engineering Group, Department of Materials Science and Engineering, Kroto Research Institute, University of Sheffield, Sheffield S3 7HQ, UK; (S.M.); (F.C.)
| | - Sheila MacNeil
- Biomaterials and Tissue Engineering Group, Department of Materials Science and Engineering, Kroto Research Institute, University of Sheffield, Sheffield S3 7HQ, UK; (S.M.); (F.C.)
| | - Frederik Claeyssens
- Biomaterials and Tissue Engineering Group, Department of Materials Science and Engineering, Kroto Research Institute, University of Sheffield, Sheffield S3 7HQ, UK; (S.M.); (F.C.)
| | - Ilida Ortega Asencio
- Bioengineering and Health Technologies Group, The School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK;
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22
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Wu Y, Zhou C, Tong X, Li S, Liu J. Histochemical localization of putative stem cells in irreversible pulpitis. Oral Dis 2021; 28:1207-1214. [PMID: 33728761 DOI: 10.1111/odi.13850] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 01/14/2021] [Accepted: 03/11/2021] [Indexed: 11/28/2022]
Abstract
OBJECTIVES Our study aimed to observe the distribution of putative stem cells in irreversible pulpitis and to investigate the expression of specific molecules. SUBJECTS AND METHODS Extracted third molar teeth were collected and divided into two groups: the normal pulp group and inflamed pulp group. Real-time PCR was applied to detect the expression of several embryonic and dentinogenic genes. The expression of mesenchymal cell markers (STRO-1, CD90, and CD146) and stromal cell-derived factor 1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) proteins was examined by immunohistochemical analysis. RESULTS The expression levels of most embryonic and dentinogenic genes were not statistically different between the two groups. Immunohistochemical analysis revealed that in inflamed pulp, cells with positive expression for STRO-1, CD90, and CD146 mainly resided in two specific niches, both adjacent to inflammatory sites: one in the pulp core and another in the odontoblast layer. SDF-1α- and CXCR4-positive cells were significantly correlated with STRO-1-positive cells. Double immunofluorescence analysis indicated that STRO-1-positive cells overlapped with SDF-1α- and CXCR4-positive cells near the inflammatory site. CONCLUSIONS This study gave a direct observation of putative stem cells distributed in irreversible pulpitis and implied a role of SDF-1α/CXCR4 signaling in stem cell-based therapies for reparative dentinogenesis.
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Affiliation(s)
- Yan Wu
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
| | - Caixia Zhou
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
| | - Xueying Tong
- Department of Geriatrics, Taihe Hospital, Hubei University of Chinese Medicine, Shiyan, China
| | - Shue Li
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
| | - Jiarong Liu
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
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23
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Nizami MZI, Nishina Y. Recent Advances in Stem Cells for Dental Tissue Engineering. ENGINEERING MATERIALS FOR STEM CELL REGENERATION 2021:281-324. [DOI: 10.1007/978-981-16-4420-7_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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24
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Granz CL, Gorji A. Dental stem cells: The role of biomaterials and scaffolds in developing novel therapeutic strategies. World J Stem Cells 2020; 12:897-921. [PMID: 33033554 PMCID: PMC7524692 DOI: 10.4252/wjsc.v12.i9.897] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/05/2020] [Accepted: 08/16/2020] [Indexed: 02/06/2023] Open
Abstract
Dental stem cells (DSCs) are self-renewable cells that can be obtained easily from dental tissues, and are a desirable source of autologous stem cells. The use of DSCs for stem cell transplantation therapeutic approaches is attractive due to their simple isolation, high plasticity, immunomodulatory properties, and multipotential abilities. Using appropriate scaffolds loaded with favorable biomolecules, such as growth factors, and cytokines, can improve the proliferation, differentiation, migration, and functional capacity of DSCs and can optimize the cellular morphology to build tissue constructs for specific purposes. An enormous variety of scaffolds have been used for tissue engineering with DSCs. Of these, the scaffolds that particularly mimic tissue-specific micromilieu and loaded with biomolecules favorably regulate angiogenesis, cell-matrix interactions, degradation of extracellular matrix, organized matrix formation, and the mineralization abilities of DSCs in both in vitro and in vivo conditions. DSCs represent a promising cell source for tissue engineering, especially for tooth, bone, and neural tissue restoration. The purpose of the present review is to summarize the current developments in the major scaffolding approaches as crucial guidelines for tissue engineering using DSCs and compare their effects in tissue and organ regeneration.
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Affiliation(s)
- Cornelia Larissa Granz
- Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster 48149, Germany
| | - Ali Gorji
- Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster 48149, Germany
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25
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Therapeutic Functions of Stem Cells from Oral Cavity: An Update. Int J Mol Sci 2020; 21:ijms21124389. [PMID: 32575639 PMCID: PMC7352407 DOI: 10.3390/ijms21124389] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 06/14/2020] [Accepted: 06/17/2020] [Indexed: 12/11/2022] Open
Abstract
Adult stem cells have been developed as therapeutics for tissue regeneration and immune regulation due to their self-renewing, differentiating, and paracrine functions. Recently, a variety of adult stem cells from the oral cavity have been discovered, and these dental stem cells mostly exhibit the characteristics of mesenchymal stem cells (MSCs). Dental MSCs can be applied for the replacement of dental and oral tissues against various tissue-damaging conditions including dental caries, periodontitis, and oral cancers, as well as for systemic regulation of excessive inflammation in immune disorders, such as autoimmune diseases and hypersensitivity. Therefore, in this review, we summarized and updated the types of dental stem cells and their functions to exert therapeutic efficacy against diseases.
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Abstract
Alagille syndrome (AGS) is a multisystem disorder classically involving liver and heart failure, characteristic vertebral and facial features and ocular abnormalities. AGS is caused by heterozygous mutations in JAG1 or NOTCH2, with variable phenotype penetrance. We report two cases of AGS in children with tooth defects characterised by green discolouration and hypomineralisation. The role of hyperbilirubinaemia (HB) in this atypical colour, a classical feature of AGS, has been well described. However, it does not totally explain the dental phenotype. As JAG1 and NOTCH2 mutations can affect bone development and considering common physiological pathways between bone and tooth mineralisation, both mutations could participate in this unusual dental phenotype. The role of HB and genetics in the development of the dental phenotype of AGS is discussed in two prototypical cases. Future research should focus on the underlying genetic component of tooth abnormalities.
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Affiliation(s)
- Anne-Laure Bonnet
- EA2496, Université de Paris, F-92120 Montrouge, France.,Department of Dentistry, AP-HP. Sorbonne Université, Paris, France
| | - Victor Greset
- Faculté d'odontologie, Université de Lorraine, Nancy, France
| | - Tiphaine Davit-Beal
- Department of Dentistry, AP-HP. Sorbonne Université, Paris, France .,Pediatric Dentistry, Université de Paris, F-92120 Montrouge, France
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27
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Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons. Cells 2020; 9:cells9030644. [PMID: 32155948 PMCID: PMC7140461 DOI: 10.3390/cells9030644] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 03/04/2020] [Accepted: 03/05/2020] [Indexed: 12/19/2022] Open
Abstract
Ameloblastomas are locally invasive and aggressive odontogenic tumors treated via surgical resection, which results in facial deformity and significant morbidity. Few studies have addressed the cellular and molecular events of ameloblastoma onset and progression, thus hampering the development of non-invasive therapeutic approaches. Tumorigenesis is driven by a plethora of factors, among which innervation has been long neglected. Recent findings have shown that innervation directly promotes tumor progression. On this basis, we investigated the molecular characteristics and neurotrophic properties of human ameloblastomas. Our results showed that ameloblastomas express dental epithelial stem cell markers, as well as components of the Notch signaling pathway, indicating persistence of stemness. We demonstrated that ameloblastomas express classical stem cell markers, exhibit stem cell potential, and form spheres. These tumors express also molecules of the Notch signaling pathway, fundamental for stem cells and their fate. Additionally, we showed that ameloblastomas express the neurotrophic factors NGF and BDNF, as well as their receptors TRKA, TRKB, and P75/NGFR, which are responsible for their innervation by trigeminal axons in vivo. In vitro studies using microfluidic devices showed that ameloblastoma cells attract and form connections with these nerves. Innervation of ameloblastomas might play a key role in the onset of this malignancy and might represent a promising target for non-invasive pharmacological interventions.
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28
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Li X, Wang L, Su Q, Ye L, Zhou X, Song D, Huang D. Highly Proliferative Immortalized Human Dental Pulp Cells Retain the Odontogenic Phenotype when Combined with a Beta-Tricalcium Phosphate Scaffold and BMP2. Stem Cells Int 2020; 2020:4534128. [PMID: 32148517 PMCID: PMC7044479 DOI: 10.1155/2020/4534128] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 01/14/2020] [Accepted: 01/22/2020] [Indexed: 02/05/2023] Open
Abstract
Human dental pulp cells (HDPCs) play a vital role in dentin formation and reparative dentinogenesis, which indicated their potential application in regenerative medicine. However, HDPCs, which can only be obtained from scarce human pulp tissues, also have a limited lifespan in vitro, and stem cells usually lose their original characteristics over a large number of passages. To overcome these challenges, we successfully immortalized human dental pulp cells using the piggyBac system which was employed to efficiently overexpress the SV40 T-Ag, and we then comprehensively described the cell biological behavior. The immortalized human dental pulp cells (iHDPCs) acquired long-term proliferative activity and expressed most HDPC markers. The iHDPCs maintained multiple differentiation potential and could be induced to differentiate into chondrogenic, osteogenic, and adipogenic cells in vitro. We also proved that the iHDPCs gained a stronger ability to migrate than the primary cells, while apoptosis was inhibited. Furthermore, highly proliferative iHDPCs displayed no oncogenicity when subcutaneously implanted into athymic nude mice. Finally, iHDPCs exhibited odontogenic differentiation ability and secreted dentin sialophosphoprotein (DSPP) when combined with a beta-tricalcium phosphate scaffold and bone morphogenetic protein-2 (BMP2) in vivo. Conclusively, the established iHDPCs are a valuable resource for mechanistic study of dental pulp cell differentiation and dental pulp injury repair, as well as for applications in tooth regeneration.
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Affiliation(s)
- Xiangfen Li
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Liu Wang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Qin Su
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Ling Ye
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Xuedong Zhou
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Dongzhe Song
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Dingming Huang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
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29
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Tian S, Wang J, Dong F, Du N, Li W, Song P, Liu Y. Concentrated Growth Factor Promotes Dental Pulp Cells Proliferation and Mineralization and Facilitates Recovery of Dental Pulp Tissue. Med Sci Monit 2019; 25:10016-10028. [PMID: 31877561 PMCID: PMC6944166 DOI: 10.12659/msm.919316] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Dental pulp cells (DPCs) play vital roles in the recovery of dental pulp tissue. Concentrated growth factor (CGF) can promote proliferation and mineralization of various cells. However, the functions of CGF on DPCs and dental pulp tissue are unclear. The object of our study was to identify the roles of CGF in DPCs proliferation and mineralization in vitro and to assess the effects of CGF on direct pulp capping in vivo. Material/Methods We performed CCK-8 and Transwell assay to detect proliferation and migration activity of DPCs. Alizarin Red staining was performed to examine mineralized nodules. Alkaline phosphatase activity test was used to measure the mineralization capacity of DPCs. We assessed the odontogenic differentiation gene expression level by Western blot and qPCR. The effect of CGF on direct pulp capping in vivo were evaluated by radiography and histopathology. Results CGF increased the number of proliferative and migratory DPCs. CGF enhanced DPCs mineralized nodules and improved the gene expression levels of DSPP, DMP-1, BSP, and ALP. CGF upregulated the protein levels of ALP, BMP2, SMAD5, Runx2, and p-Smad, and the effect could be partially reversed by Noggin. CGF promoted pulp recovery and kept its vitality in directly pulp capping. Conclusions CGF promotes DPCs proliferation and mineralization. It regulates the mineralization of DPCs via the BMP2/SMAD5/Runx2 signaling pathway. CGF can be used as the effective graft for direct pulp capping.
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Affiliation(s)
- Songbo Tian
- Department of Oral Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland)
| | - Jie Wang
- Department of Oral Pathology, College of Stomatology, Hebei Medical University, Shijiazhuang, Hebei, China (mainland)
| | - Fusheng Dong
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Hebei Medical University, Shijiazhuang, Hebei, China (mainland)
| | - Nan Du
- Department of Oral Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland)
| | - Wenjing Li
- Department of Oral Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland)
| | - Peng Song
- Department of Oral Pathology, College of Stomatology, Hebei Medical University, Shijiazhuang, Hebei, China (mainland)
| | - Yanping Liu
- Physical Examination Center, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland)
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30
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Man RC, Sulaiman N, Idrus RBH, Ariffin SHZ, Wahab RMA, Yazid MD. Insights into the Effects of the Dental Stem Cell Secretome on Nerve Regeneration: Towards Cell-Free Treatment. Stem Cells Int 2019; 2019:4596150. [PMID: 31772587 PMCID: PMC6855004 DOI: 10.1155/2019/4596150] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 08/28/2019] [Accepted: 09/16/2019] [Indexed: 12/11/2022] Open
Abstract
Cell-free treatment is emerging as an alternative to cell delivery to promote endogenous regeneration using cell-derived factors. The purpose of this article was to systematically review studies of the effects of the dental stem cell secretome on nerve regeneration. PubMed and Scopus databases were used where searched and related studies were selected. The primary search identified 36 articles with the utilized keywords; however, only 13 articles met the defined inclusion criteria. Eight out of thirteen articles included in vivo and in vitro studies. We classified the dental stem cell-derived secretome with its nerve regeneration potential. All studies demonstrated that dental stem cell-derived factors promote neurotrophic effects that can mechanistically stimulate nerve regeneration in neurodegenerative diseases and nerve injury. This data collection will enable researchers to gather information to create a precise formulation for future prescribed treatments.
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Affiliation(s)
- Rohaina Che Man
- Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia
| | - Nadiah Sulaiman
- Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia
| | - Ruszymah Bt Hj Idrus
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia
| | - Shahrul Hisham Zainal Ariffin
- Malaysia Genome Institute (MGI), National Institute of Biotechnology Malaysia (NIBM), Jalan Bangi, 43000 Bangi, Selangor, Malaysia
- Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Selangor 43600, Malaysia
| | - Rohaya Megat Abdul Wahab
- Department of Orthodontic, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia
| | - Muhammad Dain Yazid
- Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia
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31
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Liu J, Ruan J, Weir MD, Ren K, Schneider A, Wang P, Oates TW, Chang X, Xu HHK. Periodontal Bone-Ligament-Cementum Regeneration via Scaffolds and Stem Cells. Cells 2019; 8:E537. [PMID: 31167434 PMCID: PMC6628570 DOI: 10.3390/cells8060537] [Citation(s) in RCA: 167] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 05/29/2019] [Accepted: 05/29/2019] [Indexed: 12/13/2022] Open
Abstract
Periodontitis is a prevalent infectious disease worldwide, causing the damage of periodontal support tissues, which can eventually lead to tooth loss. The goal of periodontal treatment is to control the infections and reconstruct the structure and function of periodontal tissues including cementum, periodontal ligament (PDL) fibers, and bone. The regeneration of these three types of tissues, including the re-formation of the oriented PDL fibers to be attached firmly to the new cementum and alveolar bone, remains a major challenge. This article represents the first systematic review on the cutting-edge researches on the regeneration of all three types of periodontal tissues and the simultaneous regeneration of the entire bone-PDL-cementum complex, via stem cells, bio-printing, gene therapy, and layered bio-mimetic technologies. This article primarily includes bone regeneration; PDL regeneration; cementum regeneration; endogenous cell-homing and host-mobilized stem cells; 3D bio-printing and generation of the oriented PDL fibers; gene therapy-based approaches for periodontal regeneration; regenerating the bone-PDL-cementum complex via layered materials and cells. These novel developments in stem cell technology and bioactive and bio-mimetic scaffolds are highly promising to substantially enhance the periodontal regeneration including both hard and soft tissues, with applicability to other therapies in the oral and maxillofacial region.
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Affiliation(s)
- Jin Liu
- Key Laboratory of Shannxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, 98 XiWu Road, Xi'an 710004, China.
- Clinical Research Center of Shannxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi'an Jiaotong University, 98 XiWu Road, Xi'an 710004, China.
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA.
| | - Jianping Ruan
- Key Laboratory of Shannxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, 98 XiWu Road, Xi'an 710004, China.
- Clinical Research Center of Shannxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi'an Jiaotong University, 98 XiWu Road, Xi'an 710004, China.
| | - Michael D Weir
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA.
| | - Ke Ren
- Department of Neural and Pain Sciences, School of Dentistry, & Program in Neuroscience, University of Maryland, Baltimore, MD 21201, USA.
| | - Abraham Schneider
- Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
- Member, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
| | - Ping Wang
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA.
| | - Thomas W Oates
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA.
| | - Xiaofeng Chang
- Key Laboratory of Shannxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, 98 XiWu Road, Xi'an 710004, China.
- Clinical Research Center of Shannxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi'an Jiaotong University, 98 XiWu Road, Xi'an 710004, China.
| | - Hockin H K Xu
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA.
- Member, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
- Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
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32
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Serotonin in stem cell based-dental repair and bone formation: A review. Biochimie 2019; 161:65-72. [DOI: 10.1016/j.biochi.2018.07.030] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Accepted: 07/31/2018] [Indexed: 01/08/2023]
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33
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Shi C, Yuan Y, Guo Y, Jing J, Ho TV, Han X, Li J, Feng J, Chai Y. BMP Signaling in Regulating Mesenchymal Stem Cells in Incisor Homeostasis. J Dent Res 2019; 98:904-911. [PMID: 31136721 DOI: 10.1177/0022034519850812] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Bone morphogenetic protein (BMP) signaling performs multiple essential functions during craniofacial development. In this study, we used the adult mouse incisor as a model to uncover how BMP signaling maintains tissue homeostasis and regulates mesenchymal stem cell (MSC) fate by mediating WNT and FGF signaling. We observed a severe defect in the proximal region of the adult mouse incisor after loss of BMP signaling in the Gli1+ cell lineage, indicating that BMP signaling is required for cell proliferation and odontoblast differentiation. Our study demonstrates that BMP signaling serves as a key regulator that antagonizes WNT and FGF signaling to regulate MSC lineage commitment. In addition, BMP signaling in the Gli1+ cell lineage is also required for the maintenance of quiescent MSCs, suggesting that BMP signaling not only is important for odontoblast differentiation but also plays a crucial role in providing feedback to the MSC population. This study highlights multiple important roles of BMP signaling in regulating tissue homeostasis.
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Affiliation(s)
- C Shi
- 1 Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA.,2 Department of Orthodontics, The Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China
| | - Y Yuan
- 1 Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA
| | - Y Guo
- 1 Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA.,3 Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China
| | - J Jing
- 1 Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA.,4 State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - T V Ho
- 1 Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA
| | - X Han
- 1 Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA
| | - J Li
- 1 Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA.,5 Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China
| | - J Feng
- 1 Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA
| | - Y Chai
- 1 Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA
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Wu A, Bao Y, Yu H, Zhou Y, Lu Q. Berberine Accelerates Odontoblast Differentiation by Wnt/β-Catenin Activation. Cell Reprogram 2019; 21:108-114. [PMID: 30969881 DOI: 10.1089/cell.2018.0060] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Berberine, a Chinese medical herbal extract, plays a key role in antidiabetic, antiangiogenesis, anti-inflammatory, antimicrobial, anticancer, and antihypercholesterolemic. Our previous studies revealed that berberine exerted odontoprotective effect by increasing odontoblast differentiation. However, the mechanisms involved in the odontoprotective effect of berberine have not been fully explored. The Wnt/β-catenin pathway is involved in odontoblast differentiation of dental pulp stem cells (DPSCs). If β-catenin is nuclear translocation, the Wnt/β-catenin pathway is activation. In this study, DPSCs were treated with or without berberine. Then, we examined the accelerative effects of berberine on odontoblast differentiation and mineralized nodules formation by real-time polymerase chain reaction, alizarin red S staining, and alkaline phosphatase staining. In addition, while treated with berberine, β-catenin translocated to the nucleus evaluated by western blot and immunofluorescent staining. Our results revealed that berberine functions as a promoter of odontoblast differentiation by promoting Wnt/β-catenin pathway, suggesting that it may be useful in guiding therapeutic strategies for the treatment of dental caries.
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Affiliation(s)
- Anqian Wu
- 1 Department of Implantology, School of Stomatology, Jilin University, Changchun, Jilin, China
| | - Yueqi Bao
- 2 Department of Ophthalmology, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Hongqiang Yu
- 1 Department of Implantology, School of Stomatology, Jilin University, Changchun, Jilin, China
| | - Yanmin Zhou
- 1 Department of Implantology, School of Stomatology, Jilin University, Changchun, Jilin, China.,3 Department of Implantology, Stomatological Hospital of Jilin University, Changchun, Jilin, China
| | - Qi Lu
- 4 Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
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A comparative in vitro study of the osteogenic and adipogenic potential of human dental pulp stem cells, gingival fibroblasts and foreskin fibroblasts. Sci Rep 2019; 9:1761. [PMID: 30741963 PMCID: PMC6370862 DOI: 10.1038/s41598-018-37981-x] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 12/17/2018] [Indexed: 12/12/2022] Open
Abstract
Human teeth contain a variety of mesenchymal stem cell populations that could be used for cell-based regenerative therapies. However, the isolation and potential use of these cells in the clinics require the extraction of functional teeth, a process that may represent a significant barrier to such treatments. Fibroblasts are highly accessible and might represent a viable alternative to dental stem cells. We thus investigated and compared the in vitro differentiation potential of human dental pulp stem cells (hDPSCs), gingival fibroblasts (hGFs) and foreskin fibroblasts (hFFs). These cell populations were cultured in osteogenic and adipogenic differentiation media, followed by Alizarin Red S and Oil Red O staining to visualize cytodifferentiation. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was performed to assess the expression of markers specific for stem cells (NANOG, OCT-4), osteogenic (RUNX2, ALP, SP7/OSX) and adipogenic (PPAR-γ2, LPL) differentiation. While fibroblasts are more prone towards adipogenic differentiation, hDPSCs exhibit a higher osteogenic potential. These results indicate that although fibroblasts possess a certain mineralization capability, hDPSCs represent the most appropriate cell population for regenerative purposes involving bone and dental tissues.
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Marrelli M, Codispoti B, Shelton RM, Scheven BA, Cooper PR, Tatullo M, Paduano F. Dental Pulp Stem Cell Mechanoresponsiveness: Effects of Mechanical Stimuli on Dental Pulp Stem Cell Behavior. Front Physiol 2018; 9:1685. [PMID: 30534086 PMCID: PMC6275199 DOI: 10.3389/fphys.2018.01685] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Accepted: 11/08/2018] [Indexed: 12/28/2022] Open
Abstract
Dental pulp is known to be an accessible and important source of multipotent mesenchymal progenitor cells termed dental pulp stem cells (DPSCs). DPSCs can differentiate into odontoblast-like cells and maintain pulp homeostasis by the formation of new dentin which protects the underlying pulp. DPSCs similar to other mesenchymal stem cells (MSCs) reside in a niche, a complex microenvironment consisting of an extracellular matrix, other local cell types and biochemical stimuli that influence the decision between stem cell (SC) self-renewal and differentiation. In addition to biochemical factors, mechanical factors are increasingly recognized as key regulators in DPSC behavior and function. Thus, microenvironments can significantly influence the role and differentiation of DPSCs through a combination of factors which are biochemical, biomechanical and biophysical in nature. Under in vitro conditions, it has been shown that DPSCs are sensitive to different types of force, such as uniaxial mechanical stretch, cyclic tensile strain, pulsating fluid flow, low-intensity pulsed ultrasound as well as being responsive to biomechanical cues presented in the form of micro- and nano-scale surface topographies. To understand how DPSCs sense and respond to the mechanics of their microenvironments, it is essential to determine how these cells convert mechanical and physical stimuli into function, including lineage specification. This review therefore covers some aspects of DPSC mechanoresponsivity with an emphasis on the factors that influence their behavior. An in-depth understanding of the physical environment that influence DPSC fate is necessary to improve the outcome of their therapeutic application for tissue regeneration.
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Affiliation(s)
- Massimo Marrelli
- Stem Cells Unit, Biomedical Section, Tecnologica Research Institute and Marrelli Health, Crotone, Italy
| | - Bruna Codispoti
- Stem Cells Unit, Biomedical Section, Tecnologica Research Institute and Marrelli Health, Crotone, Italy
| | - Richard M. Shelton
- School of Dentistry, Institute of Clinical Sciences, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, United Kingdom
| | - Ben A. Scheven
- School of Dentistry, Institute of Clinical Sciences, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, United Kingdom
| | - Paul R. Cooper
- School of Dentistry, Institute of Clinical Sciences, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, United Kingdom
| | - Marco Tatullo
- Stem Cells Unit, Biomedical Section, Tecnologica Research Institute and Marrelli Health, Crotone, Italy
| | - Francesco Paduano
- Stem Cells Unit, Biomedical Section, Tecnologica Research Institute and Marrelli Health, Crotone, Italy
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Kichenbrand C, Velot E, Menu P, Moby V. Dental Pulp Stem Cell-Derived Conditioned Medium: An Attractive Alternative for Regenerative Therapy. TISSUE ENGINEERING PART B-REVIEWS 2018; 25:78-88. [PMID: 30156475 DOI: 10.1089/ten.teb.2018.0168] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Mesenchymal stem cells (MSC) have a lot of potential in regenerative medicine, and MSC-based therapies are currently explored in numerous research fields. Among these cells, deciduous or permanent dental pulp-MSC represent a promising option in tissue engineering. This expectation is based on their capacity to self-renew, to repair various damaged tissues and organs due to their multipotency, as well as their ability to modulate immune system. They present other advantages such as the harvesting by a simple, painless, and noninvasive procedure and the absence of ethical considerations. The role played by these cells in the reparative process is mainly attributed to paracrine mechanisms mediated by their secreted factors, namely the secretome. The secreted factors can be found in the cell culture medium, called conditioned medium (CM). Moreover, CM presents many advantages compared with cells such as possible use in allogeneic therapies. This minireview aims at investigating the therapeutic use of dental pulp MSC-derived CM to develop cell-free therapies. The analysis of the available literature illustrates its massive panel of potential applications: mainly reduction of inflammation, promotion of angiogenesis and neurogenesis, reduction of stroke or ischemia, and organ regeneration. Furthermore, studies often highlight its superiority over the other sources of CM derived from other stem cells for the same applications. Dental pulp MSC-derived CM is an attractive, noninvasive, and acellular tool for therapeutic approaches in regenerative medicine. This promising novel approach should be further explored for clinical applications.
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Affiliation(s)
- Charlène Kichenbrand
- 1 CNRS UMR 7365, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine, Biopôle de l'Université de Lorraine, Vandoeuvre-Lès-Nancy, France.,2 CHRU de Nancy-Service Odontologie, Vandœuvre-lès-Nancy, France.,3 Faculté d'Odontologie, Université de Lorraine, Nancy, France
| | - Emilie Velot
- 1 CNRS UMR 7365, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine, Biopôle de l'Université de Lorraine, Vandoeuvre-Lès-Nancy, France.,4 Faculté de Pharmacie, Nancy, France
| | - Patrick Menu
- 1 CNRS UMR 7365, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine, Biopôle de l'Université de Lorraine, Vandoeuvre-Lès-Nancy, France.,4 Faculté de Pharmacie, Nancy, France
| | - Vanessa Moby
- 1 CNRS UMR 7365, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine, Biopôle de l'Université de Lorraine, Vandoeuvre-Lès-Nancy, France.,2 CHRU de Nancy-Service Odontologie, Vandœuvre-lès-Nancy, France.,3 Faculté d'Odontologie, Université de Lorraine, Nancy, France
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Kulakov AA, Goldshtein DV, Krechina EK, Bukharova TB, Volkov AV, Gadzhiev AK. [Regeneration of dental pulp tissue using pulpal autologous mesenchymal stem cells and platelet-rich plasma]. STOMATOLOGII︠A︡ 2018; 96:12-16. [PMID: 29260758 DOI: 10.17116/stomat201796612-16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Regeneration of pulp and dentin could be important in operative dentistry as a method to save teeth. Currently cell population from dental pulp of deciduous and permanent teeth of humans and laboratory animals are isolated and characterized. The paper presents a study on pulp regeneration using autologous mesenchymal stromal cells from pulp of molars in combination with fibrin clot, transplanted in pulp chamber of miniature pigs after pulp removal. The results proved that transplantation of autologous multipotent stromal cells of dental pulp in combination with autologous platelet-rich plasma in pulp chamber of miniature pigs after pulp removal leads to pulp restoration and reparative dentinogenesis with dentinal bridge formation on the 30th day. However, the completion of regeneration also results in a decrease in the pulp chamber volume due to the neodentin bedding. Tissue regeneration of dental pulp by direct pulp capping in the absence of inflammatory processes is a promising direction of the use of cellular technologies.
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Affiliation(s)
- A A Kulakov
- Central Research Institute of Dentistry and Maxillofacial Surgery, Moscow, Russia
| | | | - E K Krechina
- Central Research Institute of Dentistry and Maxillofacial Surgery, Moscow, Russia
| | - T B Bukharova
- Research Centre for Medical Genetics, Moscow, Russia
| | - A V Volkov
- N.N. Priorov National Medical Research Centre of Traumatology and Orthopedics, Moscow, Russia
| | - A K Gadzhiev
- Central Research Institute of Dentistry and Maxillofacial Surgery, Moscow, Russia
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Dentinogenic effects of extracted dentin matrix components digested with matrix metalloproteinases. Sci Rep 2018; 8:10690. [PMID: 30013085 PMCID: PMC6048071 DOI: 10.1038/s41598-018-29112-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Accepted: 07/05/2018] [Indexed: 01/28/2023] Open
Abstract
Dentin is primarily composed of hydroxyapatite crystals within a rich organic matrix. The organic matrix comprises collagenous structural components, within which a variety of bioactive molecules are sequestered. During caries progression, dentin is degraded by acids and enzymes derived from various sources, which can release bioactive molecules with potential reparative activity towards the dentin-pulp complex. While these molecules’ repair activities in other tissues are already known, their biological effects are unclear in relation to degradation events during disease in the dentin-pulp complex. This study was undertaken to investigate the effects of dentin matrix components (DMCs) that are partially digested by matrix metalloproteinases (MMPs) in vitro and in vivo during wound healing of the dentin-pulp complex. DMCs were initially isolated from healthy dentin and treated with recombinant MMPs. Subsequently, their effects on the behaviour of primary pulp cells were investigated in vitro and in vivo. Digested DMCs modulated a range of pulp cell functions in vitro. In addition, DMCs partially digested with MMP-20 stimulated tertiary dentin formation in vivo, which exhibited a more regular tubular structure than that induced by treatment with other MMPs. Our results indicate that MMP-20 may be especially effective in stimulating wound healing of the dentin-pulp complex.
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Lew WZ, Feng SW, Lin CT, Huang HM. Use of 0.4-Tesla static magnetic field to promote reparative dentine formation of dental pulp stem cells through activation of p38 MAPK signalling pathway. Int Endod J 2018; 52:28-43. [PMID: 29869795 DOI: 10.1111/iej.12962] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Accepted: 05/30/2018] [Indexed: 11/29/2022]
Abstract
AIM To investigate whether static magnetic fields (SMFs) have a positive effect on the migration and dentinogenesis of dental pulp stem cells (DPSCs) to promote reparative dentine formation. METHODOLOGY In vitro scratch assays and a traumatic pulp exposure model were performed to evaluate the effect of 0.4-Tesla (T) SMF on DPSC migration. The cytoskeletons of the DPSCs were identified by fluorescence immunostaining and compared with those of a sham-exposed group. Dentinogenic evaluation was performed by analysing the expressions of DMP-1 and DSPP marker genes using a quantitative real-time polymerase chain reaction (qRT-PCR) process. Furthermore, the formation of calcified deposits was examined by staining the dentinogenic DPSCs with Alizarin Red S dye. Finally, the role played by the p38 MAPK signalling pathway in the migration and dentinogenesis of DPSCs under 0.4-T SMF was investigated by incorporating p38 inhibitor (SB203580) into the in vitro DPSC experiments. The Student's t-test and the Kruskal-Wallis test followed by Dunn's post hoc test with a significance level of P < 0.05 were used for statistical analysis. RESULTS The scratch assay results revealed that the application of 0.4-T SMF enhanced DPSCs migration towards the scratch wound (P < 0.05). The cytoskeletons of the SMF-treated DPSCs were found to be aligned perpendicular to the scratch wound. After 20 days of culture, the SMF-treated group had a greater number of out-grown cells than the sham-exposed group (nonmagnetized control). For the SMF-treated group, the DMP-1 (P < 0.05) and DSPP genes (P < 0.05), analysed by qRT-PCR, exhibited a higher expression. The distribution of calcified nodules was also found to be denser in the SMF-treated group when stained with Alizarin Red S dye (P < 0.05). Given the incorporation of p38 inhibitor SB203580 into the DPSCs, cell migration and dentinogenesis were suppressed. No difference was found between the SMF-treated and sham-exposed cells (P > 0.05). CONCLUSION 0.4-T SMF enhanced DPSC migration and dentinogenesis through the activation of the p38 MAPK-related pathway.
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Affiliation(s)
- W-Z Lew
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - S-W Feng
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.,School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - C-T Lin
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - H-M Huang
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.,Graduate Institute of Biomedical Optomechatronics, Taipei Medical University, Taipei, Taiwan
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Heng BC, Wang S, Gong T, Xu J, Yuan C, Zhang C. EphrinB2 signaling enhances osteogenic/odontogenic differentiation of human dental pulp stem cells. Arch Oral Biol 2018; 87:62-71. [DOI: 10.1016/j.archoralbio.2017.12.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 12/11/2017] [Accepted: 12/13/2017] [Indexed: 01/09/2023]
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Mitsiadis TA, Pagella P, Cantù C. Early Determination of the Periodontal Domain by the Wnt-Antagonist Frzb/Sfrp3. Front Physiol 2017; 8:936. [PMID: 29209231 PMCID: PMC5702314 DOI: 10.3389/fphys.2017.00936] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 11/06/2017] [Indexed: 12/21/2022] Open
Abstract
Odontogenesis results from the continuous and reciprocal interaction between cells of the oral epithelium and cranial neural crest-derived mesenchyme. The canonical Wnt signaling pathway plays a fundamental role in mediating these interactions from the earliest stages of tooth development. Here we analyze by in situ hybridization the expression patterns of the extracellular Wnt antagonist Frzb/Sfrp3. Although Frzb is expressed in dental mesenchymal cells from the earliest stages of odontogenesis, its expression is absent from a tiny population of mesenchymal cells immediately adjacent to the invaginating dental epithelium. Cell proliferation studies using BrdU showed that the Frzb expressing and Frzb non-expressing cell populations display different proliferative behavior during the initial stages of odontogenesis. DiI-mediated cell-fate tracing studies demonstrated that the Frzb expressing cells contribute to the formation of the dental follicle, the future periodontium. In contrast, the Frzb non-expressing cells give rise to the dental pulp. The present results indicate that Frzb is discriminating the presumptive periodontal territory from the rest of the dental mesenchyme from the very beginning of odontogenesis, where it might act as a barrier for the diffusion of Wnt molecules, thus regulating the activation of Wnt-dependent transcription within dental tissues.
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Affiliation(s)
- Thimios A Mitsiadis
- Orofacial Development and Regeneration, Institute of Oral Biology, Centre for Dental Medicine, Medical Faculty, University of Zurich, Zurich, Switzerland
| | - Pierfrancesco Pagella
- Orofacial Development and Regeneration, Institute of Oral Biology, Centre for Dental Medicine, Medical Faculty, University of Zurich, Zurich, Switzerland
| | - Claudio Cantù
- Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland
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Mitsiadis TA, Catón J, Pagella P, Orsini G, Jimenez-Rojo L. Monitoring Notch Signaling-Associated Activation of Stem Cell Niches within Injured Dental Pulp. Front Physiol 2017; 8:372. [PMID: 28611689 PMCID: PMC5447770 DOI: 10.3389/fphys.2017.00372] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 05/18/2017] [Indexed: 12/31/2022] Open
Abstract
Dental pulp stem/progenitor cells guarantee tooth homeostasis, repair and regeneration throughout life. The decision between renewal and differentiation of these cells is influenced by physical and molecular interactions with stromal cells and extracellular matrix molecules forming the specialized microenvironment of dental pulp stem cell niches. Here we study the activation of putative pulp niches after tooth injury through the upregulation of Notch signaling pathway. Notch1, Notch2, and Notch3 molecules were used as markers of dental pulp stem/progenitor cells. Upon dental injury, Notch1 and Notch3 are detected in cells related to vascular structures suggesting a role of these proteins in the activation of specific pulpal perivascular niches. In contrast, a population of Notch2-positive cells that are actively proliferative is observed in the apical part of the pulp. Kinetics of these cells is followed up with a lipophilic DiI labeling, showing that apical pulp cells migrate toward the injury site where dynamic regenerative/repair events occur. The knowledge of the activation and regulation of dental pulp stem/progenitor cells within their niches in pathologic conditions may be helpful for the realization of innovative dental treatments in the near future.
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Affiliation(s)
- Thimios A Mitsiadis
- Orofacial Development and Regeneration, Faculty of Medicine, Institute of Oral Biology, ZZM, University of ZurichZurich, Switzerland
| | - Javier Catón
- Department of Medical Basic Sciences, Faculty of Medicine, University CEU-San PabloMadrid, Spain
| | - Pierfrancesco Pagella
- Orofacial Development and Regeneration, Faculty of Medicine, Institute of Oral Biology, ZZM, University of ZurichZurich, Switzerland
| | - Giovanna Orsini
- Department of Clinical Sciences and Stomatology, Polytechnic University of MarcheAncona, Italy
| | - Lucia Jimenez-Rojo
- Orofacial Development and Regeneration, Faculty of Medicine, Institute of Oral Biology, ZZM, University of ZurichZurich, Switzerland
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Mitsiadis TA, Magloire H, Pagella P. Nerve growth factor signalling in pathology and regeneration of human teeth. Sci Rep 2017; 7:1327. [PMID: 28465581 PMCID: PMC5431060 DOI: 10.1038/s41598-017-01455-3] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 03/30/2017] [Indexed: 12/25/2022] Open
Abstract
Nerve growth factor (NGF) is a key regulator of the development and differentiation of neuronal and non-neuronal cells. In the present study we examined the distribution of NGF and its low and high-affinity receptors, p75NTR and TrkA respectively, in permanent human teeth under normal and pathological conditions. In intact functional teeth, NGF, p75NTR and TrkA are weakly expressed in dental pulp fibroblasts and odontoblasts that are responsible for dentine formation, while the NGF and p75NTR molecules are strongly expressed in nerve fibres innervating the dental pulp. In carious and injured teeth NGF and TrkA expression is upregulated in a selective manner in odontoblasts surrounding the injury sites, indicating a link between NGF signalling and dental tissue repair events. Accordingly, NGF and TrkA expression is strongly upregulated in cultured primary human dental mesenchymal cells during their differentiation into odontoblasts. Targeted release of NGF in cultured human tooth slices induced extensive axonal growth and migration of Schwann cells towards the NGF administration site. These results show that NGF signalling is strongly linked to pathological and regenerative processes in human teeth and suggest a potential role for this neurotrophic molecule in pulp regeneration.
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Affiliation(s)
- Thimios A Mitsiadis
- Orofacial Development and Regeneration, Institute of Oral Biology, Centre for Dental Medicine, Medical Faculty, University of Zurich, Zurich, Switzerland.
| | - Henry Magloire
- Institut de Génomique Fonctionnelle de Lyon, Ecole Normale Supérieure (ENS), Lyon, France
| | - Pierfrancesco Pagella
- Orofacial Development and Regeneration, Institute of Oral Biology, Centre for Dental Medicine, Medical Faculty, University of Zurich, Zurich, Switzerland
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Botelho J, Cavacas MA, Borrecho G, Polido M, Oliveira P, Martins Dos Santos J. Human ex vivo dentin-pulp complex preservation in a full crown model. J Oral Biol Craniofac Res 2017; 7:19-22. [PMID: 28316916 DOI: 10.1016/j.jobcr.2016.12.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Accepted: 12/11/2016] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVES Currently, there is lack of human in vitro full tooth models that hold the odontoblast layer with pulp tissue in their native environment. The appearance of new in vitro and in vivo models has provided new understanding of the potential of tissue engineering in dental pulp regeneration. However, the development of new in vitro full tooth models will allow us to get closer to in vivo conditions. Thus, the aim of this study is to preserve a living dentin-pulp complex, in a novel in vitro full crown model, after tooth extraction. METHODS Twenty intact third molars, after preparation, were divided into four groups, with five samples each. We placed the negative control samples (C) in saline, and the tested groups were placed (T) in supplemented DMEM, at two different times: 1 and 7 days. The specimens were processed for light microscopy observation. RESULTS Contrary to C-groups, T-groups showed a functional dentin-pulp complex. The treated dentin-pulp complex presents normal histological appearance. CONCLUSIONS This study showed that it is possible to preserve a living dentin-pulp complex after tooth extraction during 7 days.
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Affiliation(s)
- João Botelho
- Instituto Superior de Ciências da Saúde Egas Moniz, Anatomy Department, Campus Universitário, Quinta da Granja, Caparica, Setúbal, Portugal
| | - Maria Alzira Cavacas
- Instituto Superior de Ciências da Saúde Egas Moniz, Anatomy Department, Campus Universitário, Quinta da Granja, Caparica, Setúbal, Portugal
| | - Gonçalo Borrecho
- Instituto Superior de Ciências da Saúde Egas Moniz, Anatomy Department, Campus Universitário, Quinta da Granja, Caparica, Setúbal, Portugal
| | - Mário Polido
- Instituto Superior de Ciências da Saúde Egas Moniz, Dental Materials Department, Campus Universitário, Quinta da Granja, Caparica, Setúbal, Portugal
| | - Pedro Oliveira
- Instituto Superior de Ciências da Saúde Egas Moniz, Anatomy Department, Campus Universitário, Quinta da Granja, Caparica, Setúbal, Portugal
| | - José Martins Dos Santos
- Instituto Superior de Ciências da Saúde Egas Moniz, Anatomy Department, Campus Universitário, Quinta da Granja, Caparica, Setúbal, Portugal
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Regenerative Endodontic Procedures: A Perspective from Stem Cell Niche Biology. J Endod 2017; 43:52-62. [DOI: 10.1016/j.joen.2016.09.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 08/19/2016] [Accepted: 09/09/2016] [Indexed: 12/14/2022]
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Bakopoulou A, Leyhausen G, Geurtsen W, Koidis P. Dental Tissue Engineering Research and Translational Approaches towards Clinical Application. ORAL HEALTHCARE AND TECHNOLOGIES 2017:186-220. [DOI: 10.4018/978-1-5225-1903-4.ch004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Stem cell-based dental tissue regeneration is a new and exciting field that has the potential to transform the way that we practice dentistry. It is, however, imperative its clinical application is supported by solid basic and translational research. In this way, the full extent of the potential risks involved in the use of these technologies will be understood, and the means to prevent them will be discovered. Therefore, the aim of this chapter is to analyze the state-of-the-science with regard to dental pulp stem cell research in dental tissue engineering, the new developments in biomimetic scaffold materials customized for dental tissue applications, and to give a prospectus with respect to translational approaches of these research findings towards clinical application.
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Zhang F, Song J, Zhang H, Huang E, Song D, Tollemar V, Wang J, Wang J, Mohammed M, Wei Q, Fan J, Liao J, Zou Y, Liu F, Hu X, Qu X, Chen L, Yu X, Luu HH, Lee MJ, He TC, Ji P. Wnt and BMP Signaling Crosstalk in Regulating Dental Stem Cells: Implications in Dental Tissue Engineering. Genes Dis 2016; 3:263-276. [PMID: 28491933 PMCID: PMC5421560 DOI: 10.1016/j.gendis.2016.09.004] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling. Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance, essential oral functions and the quality of life. Regenerative dentistry holds great promise in treating oral/dental disorders. The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells, along with the signaling mechanisms governing stem cell self-renewal and differentiation. In this review, we first summarize the biological characteristics of seven types of dental stem cells, including dental pulp stem cells, stem cells from apical papilla, stem cells from human exfoliated deciduous teeth, dental follicle precursor cells, periodontal ligament stem cells, alveolar bone-derived mesenchymal stem cells (MSCs), and MSCs from gingiva. We then focus on how these stem cells are regulated by bone morphogenetic protein (BMP) and/or Wnt signaling by examining the interplays between these pathways. Lastly, we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways. We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications. Thus, we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade.
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Affiliation(s)
- Fugui Zhang
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, and the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing 401147, China.,Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Jinglin Song
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, and the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing 401147, China
| | - Hongmei Zhang
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, and the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing 401147, China.,Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Enyi Huang
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, and the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing 401147, China.,Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Dongzhe Song
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.,Department of Conservative Dentistry and Endodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, China
| | - Viktor Tollemar
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Jing Wang
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.,Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China
| | - Jinhua Wang
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, and the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing 401147, China.,Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Maryam Mohammed
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Qiang Wei
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.,Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China
| | - Jiaming Fan
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.,Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China
| | - Junyi Liao
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.,Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China
| | - Yulong Zou
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.,Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China
| | - Feng Liu
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.,Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China
| | - Xue Hu
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.,Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China
| | - Xiangyang Qu
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.,Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China
| | - Liqun Chen
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.,Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China
| | - Xinyi Yu
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.,Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China
| | - Hue H Luu
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Michael J Lee
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Tong-Chuan He
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, and the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing 401147, China.,Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.,Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China
| | - Ping Ji
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, and the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing 401147, China
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Karamzadeh R, Baghaban Eslaminejad M, Sharifi-Zarchi A. Comparative In Vitro Evaluation of Human Dental Pulp and Follicle Stem Cell Commitment. CELL JOURNAL 2016; 18:609-618. [PMID: 28042545 PMCID: PMC5086339 DOI: 10.22074/cellj.2016.4727] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/17/2015] [Accepted: 02/22/2016] [Indexed: 01/09/2023]
Abstract
Objective Pulp and periodontal tissues are well-known sources of mesenchymal stem cells
(MSCs) that provide a promising place in tissue engineering and regenerative medicine. The
molecular mechanisms underlying commitment and differentiation of dental stem cells that originate from different dental tissues are not fully understood. In this study, we have compared the
expression levels of pluripotency factors along with immunological and developmentally-related
markers in the culture of human dental pulp stem cells (hDPSCs), human dental follicle stem
cells (hDFSCs), and human embryonic stem cells (hESCs).
Materials and Methods In this experimental study, isolated human dental stem cells
were investigated using quantitative polymerase chain reaction (qPCR), immunostaining,
and fluorescence-activated cell sorting (FACS). Additionally, we conducted gene ontology
(GO) analysis of differentially expressed genes and compared them between dental stem
cells and pluripotent stem cells.
Results The results demonstrated that pluripotency (OCT4 and SOX2) and immunological
(IL-6 and TLR4) factors had higher expressions in hDFSCs, with the exception of the JAGGED-1/NOTCH1 ratio, c-MYC and NESTIN which expressed more in hDPSCs. Immunostaining of
OCT4, SOX2 and c-MYC showed cytoplasmic and nucleus localization in both groups at
similar passages. GO analysis showed that the majority of hDFSCs and hDPSCs populations
were in the synthesis (S) and mitosis (M) phases of the cell cycle, respectively.
Conclusion This study showed different status of heterogeneous hDPSCs and hDFSCs
in terms of stemness, differentiation fate, and cell cycle phases. Therefore, the different
behaviors of dental stem cells should be considered based on clinical treatment variations.
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Affiliation(s)
- Razieh Karamzadeh
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Mohamadreza Baghaban Eslaminejad
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Ali Sharifi-Zarchi
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
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