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Abdi SMY, Al-Bakri SSM, Nordin N. Insights on the Characteristics and Therapeutic Potential of Mesenchymal Stem Cell-derived Exosomes for Mitigation of Alzheimer's Disease's Pathogenicity: A Systematic Review. Cell Biochem Biophys 2025; 83:1399-1414. [PMID: 39436580 DOI: 10.1007/s12013-024-01598-x] [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] [Accepted: 04/22/2024] [Indexed: 10/23/2024]
Abstract
Alzheimer's disease (AD) remains a progressive neurodegenerative disease with no cure. Treatment of AD relies on administering drugs that only subside the symptoms. In recent studies, mesenchymal stem cell (MSC)-exosomes have been marked to possess therapeutic potential for treating AD. This study aims to systematically review and analyse findings that focus on the isolation, characterisation, and sources of MSC-derived exosomes used to unravel the therapeutic potential of these exosomes targeting AD using in vitro and in vivo models. It is hypothesised that MSC-exosomes exhibit high therapeutic potential for AD treatment by exerting various modes of action. PubMed, Scopus, and Medline were used to find relevant published works from January 2016 until December 2020, using assigned keywords including "Alzheimer's disease", "secretome", and "exosomes". Only research articles meeting the predefined inclusion/exclusion criteria were selected and analysed. The risk of bias was assessed using the Office of Health Assessment and Translation tool (OHAT). A total of 17 eligible in vivo and in vitro studies were included in this review. Bone marrow-derived stem cells (BMSCs) were the most used source for exosome isolation, even though studies on exosomes from adipose-derived stem cells (ADSCs) and human umbilical cord stem cells (HUCSCs) provide more information on the characteristics. When the risk of bias was assessed, the studies presented various levels of biases. Notably, the in vitro and in vivo studies revealed neuroprotective properties of MSC-exosomes through different modes of action to alleviate AD pathology. Our review discovered that most MSC exosomes could degrade Aβ plaques, enhance neurogenesis, extenuate neuroinflammatory response through microglial activation, regulate apoptosis and reduce oxidative stress. Delivery of exosomal micro-RNAs was also found to reduce neuroinflammation. Findings from this review provided convincing systematic evidence highlighting the therapeutic properties of MSC-derived exosomes as a prospective source for cell-free (acellular) therapy in treating AD.
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Affiliation(s)
- Sarah Mohammed Yousuf Abdi
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia
| | - Siti Sarah Mustaffa Al-Bakri
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia
| | - Norshariza Nordin
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia.
- Malaysian Research Institute on Ageing (MyAgeing™), Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
- Genetics & Regenerative Medicine (ReGEN) Research Group, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia.
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Xu X, Fu J, Yang G, Chen Z, Chen S, Yuan G. Dentin sialoprotein promotes endothelial differentiation of dental pulp stem cells through DSP aa34-50-endoglin-AKT1 axis. J Biol Chem 2025; 301:108380. [PMID: 40049415 PMCID: PMC11997338 DOI: 10.1016/j.jbc.2025.108380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 02/25/2025] [Accepted: 02/27/2025] [Indexed: 04/01/2025] Open
Abstract
Dentin sialoprotein (DSP), a major dentin extracellular matrix noncollagenous protein, is well recognized as an important regulator for dentinogenesis. DSP as a secreted protein can interact with membrane receptors, activate intracellular signaling, and initiate the odontoblastic differentiation of dental papilla cells. In a recent study, we have demonstrated that DSP can induce the endothelial differentiation of dental pulp stem cells (DPSCs), a type of tooth pulp-derived multipotent stem cells, dependent on membrane receptor endoglin (ENG). However, the intimate mechanisms by which DSP-ENG association facilitates the endothelial differentiation of DPSCs remain enigmatic. Here, we find that the amino acid (aa) residues 34-50 of DSP (DSPaa34-50) is responsible for its association with ENG using a series of co-immunoprecipitation assays. Immunofluorescent staining and in situ proximity ligation assay demonstrate that overexpressed ENG in human embryonic kidney 293T cells shows codistribution and proximity ligation assay signals to the supplemented DSPaa34-50 protein but not to DSP without aa34-50 (DSPΔ34-50) on cell surfaces. Moreover, the zona pellucida domain of ENG mediates its association with DSPaa34-50. Further experiments indicate that DSPaa34-50 exhibits equivalent effects to the full-length DSP on the migration and endothelial differentiation of DPSCs dependent on ENG but DSPΔ34-50 does not. Mechanistically, DSPaa34-50 activates AKT1 and triggers the expression of blood vessel development-related genes in DPSCs. Multiple experiments demonstrate that AKT1 inhibition suppresses the DSPaa34-50-induced migration and endothelial differentiation of DPSCs. Thus, AKT1 mediates the cellular and molecular functions of DSPaa34-50-ENG association. Collectively, these findings identify that DSP promotes the endothelial differentiation of DPSCs through the DSPaa34-50-ENG-AKT1 signaling axis.
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Affiliation(s)
- Ximin Xu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, Hubei, China
| | - Jing Fu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, Hubei, China
| | - Guobin Yang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - Zhi Chen
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - Shuo Chen
- Department of Developmental Dentistry, School of Dentistry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
| | - Guohua Yuan
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, Hubei, China.
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3
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Kim D, Kim SG. Cell Homing Strategies in Regenerative Endodontic Therapy. Cells 2025; 14:201. [PMID: 39936992 PMCID: PMC11817319 DOI: 10.3390/cells14030201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 01/24/2025] [Accepted: 01/28/2025] [Indexed: 02/13/2025] Open
Abstract
Cell homing, a process that leverages the body's natural ability to recruit cells and repair damaged tissues, presents a promising alternative to cell transplantation methods. Central to this approach is the recruitment of endogenous stem/progenitor cells-such as those from the apical papilla, bone marrow, and periapical tissues-facilitated by chemotactic biological cues. Moreover, biomaterial scaffolds embedded with signaling molecules create supportive environments, promoting cell migration, adhesion, and differentiation for the regeneration of the pulp-dentin complex. By analyzing in vivo animal studies using cell homing strategies, this review explores how biomolecules and scaffold materials enhance the recruitment of endogenous stem cells to the site of damaged dental pulp tissue, thereby promoting repair and regeneration. It also examines the key principles, recent advancements, and current limitations linked to cell homing-based regenerative endodontic therapy, highlighting the interplay of biomaterials, signaling molecules, and their broader clinical implications.
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Affiliation(s)
- David Kim
- Center for Dental and Craniofacial Research, Columbia University College of Dental Medicine, New York, NY 10032, USA;
| | - Sahng G. Kim
- Division of Endodontics, Columbia University College of Dental Medicine, New York, NY 10032, USA
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4
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Pan Y, Yang X, Chen M, Shi K, Lyu Y, Meeson AP, Lash GE. Role of Cancer Side Population Stem Cells in Ovarian Cancer Angiogenesis. Med Princ Pract 2024; 33:403-413. [PMID: 39068919 PMCID: PMC11460956 DOI: 10.1159/000539642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 06/03/2024] [Indexed: 07/30/2024] Open
Abstract
Ovarian cancer is one of the most common gynecologic malignancies. Recurrence and metastasis often occur after treatment, and it has the highest mortality rate of all gynecological tumors. Cancer stem cells (CSCs) are a small population of cells with the ability of self-renewal, multidirectional differentiation, and infinite proliferation. They have been shown to play an important role in tumor growth, metastasis, drug resistance, and angiogenesis. Ovarian cancer side population (SP) cells, a type of CSC, have been shown to play roles in tumor formation, colony formation, xenograft tumor formation, ascites formation, and tumor metastasis. The rapid progression of tumor angiogenesis is necessary for tumor growth; however, many of the mechanisms driving this process are unclear as is the contribution of CSCs. The aim of this review was to document the current state of knowledge of the molecular mechanism of ovarian cancer stem cells (OCSCs) in regulating tumor angiogenesis.
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Affiliation(s)
- Yue Pan
- Division of Uterine Vascular Biology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - XueFen Yang
- Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Miaojuan Chen
- Division of Uterine Vascular Biology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Kun Shi
- Department of Obstetrics and Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Yuan Lyu
- Medical Research Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Joint International Laboratory of Glioma Metabolism and Microenvironment Research, Henan Provincial Department of Science and Technology, Zhengzhou, China
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, China
| | | | - Gendie E. Lash
- Division of Uterine Vascular Biology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
- Department of Obstetrics and Gynecology, Third Affiliate Hospital of Zhengzhou University, Zhengzhou, China
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5
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Shekatkar M, Kheur S, Deshpande S, Sanap A, Kharat A, Navalakha S, Gupta A, Kheur M, Bhonde R, Merchant YP. Angiogenic Potential of Various Oral Cavity-Derived Mesenchymal Stem Cells and Cell-Derived Secretome: A Systematic Review and Meta-Analysis. Eur J Dent 2024; 18:712-742. [PMID: 37995732 PMCID: PMC11290931 DOI: 10.1055/s-0043-1776315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2023] Open
Abstract
Recent evidence suggests the immense potential of human mesenchymal stem cell (hMSC) secretome conditioned medium-mediated augmentation of angiogenesis. However, angiogenesis potential varies from source and origin. The hMSCs derived from the oral cavity share an exceptional quality due to their origin from a hypoxic environment. Our systematic review aimed to compare the mesenchymal stem cells (MSCs) derived from various oral cavity sources and cell-derived secretomes, and evaluate their angiogenic potential. A literature search was conducted using PubMed and Scopus from January 2000 to September 2020. Source-wise outcomes were systematically analyzed using in vitro, in vivo, and in ovo studies, emphasizing endothelial cell migration, tube formation, and blood vessel formation. Ninety-four studies were included in the systematic review, out of which 4 studies were subsequently included in the meta-analysis. Prominent growth factors and other bioactive components implicated in improving angiogenesis were included in the respective studies. The findings suggest that oral tissues are a rich source of hMSCs. The meta-analysis revealed a positive correlation between dental pulp-derived MSCs (DPMSCs) and stem cells derived from apical papilla (SCAP) compared to human umbilical cord-derived endothelial cell lines as a control. It shows a statistically significant positive correlation between the co-culture of human umbilical vein endothelial cells (HUVECs) and DPMSCs with tubule length formation and total branching points. Our meta-analysis revealed that oral-derived MSCs (dental pulp stem cells and SCAP) carry a better angiogenic potential in vitro than endothelial cell lines alone. The reviewed literature illustrates that oral cavity-derived MSCs (OC-MSCs) increased angiogenesis. The present literature reveals a dearth of investigations involving sources other than dental pulp. Even though OC-MSCs have revealed more significant potential than other MSCs, more comprehensive, target-oriented interinstitutional prospective studies are warranted to determine whether oral cavity-derived stem cells are the most excellent sources of significant angiogenic potential.
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Affiliation(s)
- Madhura Shekatkar
- Department of Oral Pathology and Microbiology, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India
| | - Supriya Kheur
- Department of Oral Pathology and Microbiology, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India
| | - Shantanu Deshpande
- Department of Pediatric and Preventive Dentistry, Bharati Vidyapeeth (Deemed to be) University Dental College and Hospital, Navi Mumbai, India
| | - Avinash Sanap
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India
| | - Avinash Kharat
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India
| | - Shivani Navalakha
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India
| | - Archana Gupta
- Department of Oral Pathology and Microbiology, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India
| | - Mohit Kheur
- Department of Prosthodontics, M.A. Rangoonwala College of Dental Sciences and Research Centre, Pune, India
| | | | - Yash P. Merchant
- Department of Oral and Maxillofacial Surgery, Dr. D. Y. Patil Dental College, and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India
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Abdolahinia ED, Golestani S, Seif S, Afra N, Aflatoonian K, Jalalian A, Valizadeh N, Abdollahinia ED. A review of the therapeutic potential of dental stem cells as scaffold-free models for tissue engineering application. Tissue Cell 2024; 86:102281. [PMID: 38070384 DOI: 10.1016/j.tice.2023.102281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 11/19/2023] [Accepted: 11/22/2023] [Indexed: 01/21/2024]
Abstract
In the realm of regenerative medicine, tissue engineering has introduced innovative approaches to facilitate tissue regeneration. Specifically, in pulp tissue engineering, both scaffold-based and scaffold-free techniques have been applied. Relevant articles were meticulously chosen from PubMed, Scopus, and Google Scholar databases through a comprehensive search spanning from October 2022 to December 2022. Despite the inherent limitations of scaffolding, including inadequate mechanical strength for hard tissues, insufficient vents for vessel penetration, immunogenicity, and suboptimal reproducibility-especially with natural polymeric scaffolds-scaffold-free tissue engineering has garnered significant attention. This methodology employs three-dimensional (3D) cell aggregates such as spheroids and cell sheets with extracellular matrix, facilitating precise regeneration of target tissues. The choice of technique aside, stem cells play a pivotal role in tissue engineering, with dental stem cells emerging as particularly promising resources. Their pluripotent nature, non-invasive extraction process, and unique properties render them highly suitable for scaffold-free tissue engineering. This study delves into the latest advancements in leveraging dental stem cells and scaffold-free techniques for the regeneration of various tissues. This paper offers a comprehensive summary of recent developments in the utilization of dental stem cells and scaffold-free methods for tissue generation. It explores the potential of these approaches to advance tissue engineering and their effectiveness in therapies aimed at tissue regeneration.
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Affiliation(s)
- Elaheh Dalir Abdolahinia
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Oral Science and Translation Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
| | - Shayan Golestani
- Department of Oral and Maxillofacial Surgery, Dental School, Islamic Azad University, Isfahan ( Khorasgan) Branch, Isfahan, Iran
| | - Sepideh Seif
- Faculty of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Narges Afra
- Faculty of Dentistry, Hormozgan University of Medical Sciences, Bandarabbas, Iran
| | - Khotan Aflatoonian
- Department of Restorative Dentistry, Dental School, Shahed University of Medical Sciences, Tehran, Iran
| | - Ali Jalalian
- Faculty of Dentistry, Hamedan University of Medical Sciences, Hamedan, Iran
| | - Nasrin Valizadeh
- Chemistry Department, Sciences Faculty, Azarbaijan Shahid Madani University, Tabriz, Iran
| | - Elham Dalir Abdollahinia
- Fellowship of Endocrinology, Endocrinology Department, Tabriz University of Medical Sciences, Iran.
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7
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Ledford BT, Chen M, Van Dyke M, Barron C, Zhang X, Cartaya A, Zheng Y, Ceylan A, Goldstein A, He JQ. Keratose Hydrogel Drives Differentiation of Cardiac Vascular Smooth Muscle Progenitor Cells: Implications in Ischemic Treatment. Stem Cell Rev Rep 2023; 19:2341-2360. [PMID: 37392292 DOI: 10.1007/s12015-023-10574-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/08/2023] [Indexed: 07/03/2023]
Abstract
Peripheral artery disease (PAD) is a common vascular disorder in the extremity of limbs with limited clinical treatments. Stem cells hold great promise for the treatment of PAD, but their therapeutic efficiency is limited due to multiple factors, such as poor engraftment and non-optimal selection of cell type. To date, stem cells from a variety of tissue sources have been tested, but little information is available regarding vascular smooth muscle cells (VSMCs) for PAD therapy. The present study examines the effects of keratose (KOS) hydrogels on c-kit+/CD31- cardiac vascular smooth muscle progenitor cell (cVSMPC) differentiation and the therapeutic potential of the resultant VSMCs in a mouse hindlimb ischemic model of PAD. The results demonstrated that KOS but not collagen hydrogel was able to drive the majority of cVSMPCs into functional VSMCs in a defined Knockout serum replacement (SR) medium in the absence of differentiation inducers. This effect could be inhibited by TGF-β1 antagonists. Further, KOS hydrogel increased expression of TGF-β1-associated proteins and modulated the level of free TGF-β1 during differentiation. Finally, transplantation of KOS-driven VSMCs significantly increased blood flow and vascular densities of ischemic hindlimbs. These findings indicate that TGF-β1 signaling is involved in KOS hydrogel-preferred VSMC differentiation and that enhanced blood flow are likely resulted from angiogenesis and/or arteriogenesis induced by transplanted VSMCs.
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Affiliation(s)
- Benjamin T Ledford
- Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061, USA
| | - Miao Chen
- Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061, USA
| | - Mark Van Dyke
- Department of Biomedical Engineering, College of Engineering, University of Arizona, Tucson, AZ, 85721, USA
| | - Catherine Barron
- Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061, USA
| | - Xiaonan Zhang
- Beijing Yulong Shengshi Biotechnology, Haidian District, Beijing, 100085, China
| | - Aurora Cartaya
- Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061, USA
| | - Youjing Zheng
- Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061, USA
| | - Ahmet Ceylan
- Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061, USA
| | - Aaron Goldstein
- Department of Chemical Engineering, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA, 24061, USA
| | - Jia-Qiang He
- Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061, USA.
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Rathinam E, Rajasekharan S, Declercq H, Vanhove C, De Coster P, Martens L. Effect of Intracoronal Sealing Biomaterials on the Histological Outcome of Endodontic Revitalisation in Immature Sheep Teeth-A Pilot Study. J Funct Biomater 2023; 14:jfb14040214. [PMID: 37103304 PMCID: PMC10144940 DOI: 10.3390/jfb14040214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/17/2023] [Accepted: 04/08/2023] [Indexed: 04/28/2023] Open
Abstract
The influence of intracoronal sealing biomaterials on the newly formed regenerative tissue after endodontic revitalisation therapy remains unexplored. The objective of this study was to compare the gene expression profiles of two different tricalcium silicate-based biomaterials alongside the histological outcomes of endodontic revitalisation therapy in immature sheep teeth. The messenger RNA expression of TGF-β, BMP2, BGLAP, VEGFA, WNT5A, MMP1, TNF-α and SMAD6 was evaluated after 1 day with qRT-PCR. For evaluation of histological outcomes, revitalisation therapy was performed using Biodentine (n = 4) or ProRoot white mineral trioxide aggregate (WMTA) (n = 4) in immature sheep according to the European Society of Endodontology position statement. After 6 months' follow-up, one tooth in the Biodentine group was lost to avulsion. Histologically, extent of inflammation, presence or absence of tissue with cellularity and vascularity inside the pulp space, area of tissue with cellularity and vascularity, length of odontoblast lining attached to the dentinal wall, number and area of blood vessels and area of empty root canal space were measured by two independent investigators. All continuous data were subjected to statistical analysis using Wilcoxon matched-pairs signed rank test at a significance level of p < 0.05. Biodentine and ProRoot WMTA upregulated the genes responsible for odontoblast differentiation, mineralisation and angiogenesis. Biodentine induced the formation of a significantly larger area of neoformed tissue with cellularity, vascularity and increased length of odontoblast lining attached to the dentinal walls compared to ProRoot WMTA (p < 0.05), but future studies with larger sample size and adequate power as estimated by the results of this pilot study would confirm the effect of intracoronal sealing biomaterials on the histological outcome of endodontic revitalisation.
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Affiliation(s)
- Elanagai Rathinam
- ELOHA (Equal Lifelong Oral Health for All) Research Group, Paediatric Dentistry, Oral Health Sciences, Ghent University Hospital, 9000 Ghent, Belgium
| | - Sivaprakash Rajasekharan
- ELOHA (Equal Lifelong Oral Health for All) Research Group, Paediatric Dentistry, Oral Health Sciences, Ghent University Hospital, 9000 Ghent, Belgium
| | - Heidi Declercq
- Tissue Engineering and Biomaterials Group, Department of Human Structure and Repair, Ghent University Hospital, Ghent University, 9000 Ghent, Belgium
- Tissue Engineering Laboratory, Department of Development and Regeneration, KU Leuven, 8500 Kortrijk, Belgium
| | - Christian Vanhove
- Medical Imaging & Signal Processing, Infinity Laboratory, Ghent University Hospital, Ghent University, 9000 Ghent, Belgium
| | - Peter De Coster
- Department of Reconstructive Dentistry and Oral Biology, Dental School, Ghent University Hospital, Ghent University, 9000 Ghent, Belgium
| | - Luc Martens
- ELOHA (Equal Lifelong Oral Health for All) Research Group, Paediatric Dentistry, Oral Health Sciences, Ghent University Hospital, 9000 Ghent, Belgium
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9
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Encapsulation of human endometrial stem cells in chitosan hydrogel containing titanium oxide nanoparticles for dental pulp repair and tissue regeneration in male Wistar rats. J Biosci Bioeng 2023; 135:331-340. [PMID: 36709084 DOI: 10.1016/j.jbiosc.2022.12.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 12/16/2022] [Accepted: 12/19/2022] [Indexed: 01/27/2023]
Abstract
This study aimed to determine the impact of human endometrial stem cells (EnSCs) and titanium oxide nanoparticles (TiO2 NPs) on dental pulp repair and regeneration in an animal model through dentine development and tissue regeneration. The EnSCs were put on a three-dimensional (3D) chitosan scaffold containing TiO2 NPs after obtaining and purifying the collagenase enzyme. Pulps were exposed on the maxillary left first molar of all rats followed by direct pulp capping with the experimental scaffolds, as follows. Groups were: 1, control group without any treatment; 2, chitosan group (CS); 3, chitosan group with stem cells (CS/SCs); 4, chitosan group with stem cells and TiO2 NPs (CS/EnSCs/TiO2). Glass ionomer was used as a sealant in all groups. The teeth were extracted and histologically evaluated after 8 weeks. The quality and amount of dentine in the CS/EnSCs/TiO2 group were higher than in the other groups. The combination of EnSCs with TiO2 NPs and 3D chitosan scaffolds had a synergistic effect on each other, evidencing increased speed and quality of dentine formation. Using EnSCs with TiO2 NPs on a 3D chitosan scaffold can be a suitable combination for direct pulp capping and dentine regeneration in a rat molar tooth model.
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10
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Gomez-Sosa JF, Cardier JE, Caviedes-Bucheli J. The hypoxia-dependent angiogenic process in dental pulp. J Oral Biosci 2022; 64:381-391. [PMID: 35998752 DOI: 10.1016/j.job.2022.08.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 08/09/2022] [Accepted: 08/15/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND In this review, we analyzed the existing literature to elucidate how the hypoxia-dependent angiogenic processes work in dental pulp. Angiogenesis is an essential biological process in the maturation and homeostasis of teeth. It involves multiple sequential steps such as endothelial cell proliferation and migration, cell-to-cell contact, and tube formation. HIGHLIGHT Clinical implications of understanding the process of angiogenesis include how the mineralization processes of dental pulp occur and how dental pulp maintains its homeostasis, preventing irreversible inflammation or necrosis. CONCLUSION The angiogenesis process in dental pulp regulates adequate concentrations of oxygen required for mineralization in root development and defense mechanisms against chronic stimuli.
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Affiliation(s)
- Jose Francisco Gomez-Sosa
- Unidad de Terapia Celular - Centro de Medicina Regenerativa, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas-Venezuela.
| | - Jose E Cardier
- Unidad de Terapia Celular - Centro de Medicina Regenerativa, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas-Venezuela
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11
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Chouaib B, Cuisinier F, Collart-Dutilleul PY. Dental stem cell-conditioned medium for tissue regeneration: Optimization of production and storage. World J Stem Cells 2022; 14:287-302. [PMID: 35662860 PMCID: PMC9136565 DOI: 10.4252/wjsc.v14.i4.287] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 05/19/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSC) effects on tissue regeneration are mainly mediated by their secreted substances (secretome), inducing their paracrine activity. This Conditioned medium (CM), including soluble factors (proteins, nucleic acids, lipids) and extracellular vesicles is emerging as a potential alternative to cell therapy. However, the manufacturing of CM suffers from variable procedures and protocols leading to varying results between studies. Besides, there is no well-defined optimized procedure targeting specific applications in regenerative medicine. AIM To focus on conditioned medium produced from dental MSC (DMSC-CM), we reviewed the current parameters and manufacturing protocols, in order to propose a standardization and optimization of these manufacturing procedures. METHODS We have selected all publications investigating the effects of dental MSC secretome in in vitro and in vivo models of tissue regeneration, in accordance with the PRISMA guidelines. RESULTS A total of 351 results were identified. And based on the inclusion criteria described above, 118 unique articles were included in the systematic review. DMSC-CM production was considered at three stages: before CM recovery (cell sources for CM), during CM production (culture conditions) and after production (CM treatment). CONCLUSION No clear consensus could be recovered as evidence-based methods, but we were able to describe the most commonly used protocols: donors under 30 years of age, dental pulp stem cells and exfoliated deciduous tooth stem cells with cell passage between 1 and 5, at a confluence of 70% to 80%. CM were often collected during 48 h, and stored at -80 °C. It is important to point out that the preconditioning environment had a significant impact on DMSC-CM content and efficiency.
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Affiliation(s)
- Batoul Chouaib
- Laboratory Bioengineering and Nanosciences UR_UM104, University of Montpellier, Montpellier 34000, France
| | - Frédéric Cuisinier
- Laboratory Bioengineering and Nanosciences UR_UM104, University of Montpellier, Montpellier 34000, France
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12
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Yong Z, Kuang G, Fengying S, Shoumei X, Duohong Z, Jiacai H, Xuyan T. Comparison of the Angiogenic Ability between SHED and DPSC in a Mice Model with Critical Limb Ischemic. Tissue Eng Regen Med 2022; 19:861-870. [PMID: 35474506 PMCID: PMC9294125 DOI: 10.1007/s13770-022-00452-6] [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: 01/08/2022] [Revised: 02/14/2022] [Accepted: 03/09/2022] [Indexed: 10/18/2022] Open
Abstract
BACKGROUND Regenerative medicine by using stem cells from dental pulp is promising for treating patients with critical limb ischemic (CLI). Here, we investigated the difference in the angiogenetic ability of stem cells from human exfoliated deciduous teeth (SHED) and human dental pulp stem cells (DPSC). METHODS SHED and DPSC were harvested from dental pulp and analyzed in flow- cytometry for detecting the expression of surface markers. Levels of angiogenetic marker were examined by RT-PCR and Western-blot. Eighteen immunodeficient mice of critical limb ischemic model were divided into three groups: SHED, DPSC and saline, which was administered with SHED, DPSC or saline intramuscularly. Histological examination was performed to detect the regenerative results. RESULTS A highly expression of CD146 was detected in SHED. Moreover, cells with negative expression of both CD146 and CD31 in SHED were more in comparison with those in DPSC. Expression of angiogenesis factors including CXCL12, CXCR4, Hif-1a, CD31, VEGF and bFGF were significant higher in SHED than DPSC by the RT-PCR and Western-Blot results. SHED induced more CD31 expression and less fibrous tissue formation in the critical limb ischemic model as compare with DPSC and saline. CONCLUSION Both SHED and DPSC possessed the ability of repairing CLI. With expressing more proangiogenesis factors, SHED may have the advantage of repairing CLI.
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Affiliation(s)
- Zhou Yong
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.,Department of Dental Implantology, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China.,Periodontal Department College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Gu Kuang
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.,Periodontal Department College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Sun Fengying
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.,Periodontal Department College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Xuan Shoumei
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.,Periodontal Department College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Zou Duohong
- Department of Oral Surgery, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of Stomatology, School of Medicine, Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200011, China.,Periodontal Department College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - He Jiacai
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.,Department of Dental Implantology, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China.,Periodontal Department College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Tang Xuyan
- College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.
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13
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Kwack KH, Lee HW. Clinical Potential of Dental Pulp Stem Cells in Pulp Regeneration: Current Endodontic Progress and Future Perspectives. Front Cell Dev Biol 2022; 10:857066. [PMID: 35478967 PMCID: PMC9035692 DOI: 10.3389/fcell.2022.857066] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 03/18/2022] [Indexed: 12/12/2022] Open
Abstract
Dental caries is a common disease that not only destroys the rigid structure of the teeth but also causes pulp necrosis in severe cases. Once pulp necrosis has occurred, the most common treatment is to remove the damaged pulp tissue, leading to a loss of tooth vitality and increased tooth fragility. Dental pulp stem cells (DPSCs) isolated from pulp tissue exhibit mesenchymal stem cell-like characteristics and are considered ideal candidates for regenerating damaged dental pulp tissue owing to their multipotency, high proliferation rate, and viability after cryopreservation. Importantly, DPSCs do not elicit an allogeneic immune response because they are non-immunogenic and exhibit potent immunosuppressive properties. Here, we provide an up-to-date review of the clinical applicability and potential of DPSCs, as well as emerging trends in the regeneration of damaged pulp tissue. In addition, we suggest the possibility of using DPSCs as a resource for allogeneic transplantation and provide a perspective for their clinical application in pulp regeneration.
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Affiliation(s)
- Kyu Hwan Kwack
- Department of Dentistry, Graduate School, Kyung Hee University, Seoul, South Korea
| | - Hyeon-Woo Lee
- Department of Pharmacology, School of Dentistry, Graduate School, Institute of Oral Biology, Kyung Hee University, Seoul, South Korea
- *Correspondence: Hyeon-Woo Lee,
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14
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Hariharan A, Iyer J, Wang A, Tran SD. Tracking of Oral and Craniofacial Stem Cells in Tissue Development, Regeneration, and Diseases. Curr Osteoporos Rep 2021; 19:656-668. [PMID: 34741728 DOI: 10.1007/s11914-021-00705-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/15/2021] [Indexed: 10/19/2022]
Abstract
PURPOSE OF REVIEW The craniofacial region hosts a variety of stem cells, all isolated from different sources of bone and cartilage. However, despite scientific advancements, their role in tissue development and regeneration is not entirely understood. The goal of this review is to discuss recent advances in stem cell tracking methods and how these can be advantageously used to understand oro-facial tissue development and regeneration. RECENT FINDINGS Stem cell tracking methods have gained importance in recent times, mainly with the introduction of several molecular imaging techniques, like optical imaging, computed tomography, magnetic resonance imaging, and ultrasound. Labelling of stem cells, assisted by these imaging techniques, has proven to be useful in establishing stem cell lineage for regenerative therapy of the oro-facial tissue complex. Novel labelling methods complementing imaging techniques have been pivotal in understanding craniofacial tissue development and regeneration. These stem cell tracking methods have the potential to facilitate the development of innovative cell-based therapies.
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Affiliation(s)
- Arvind Hariharan
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC, H3A 0C7, Canada
| | - Janaki Iyer
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC, H3A 0C7, Canada
| | - Athena Wang
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC, H3A 0C7, Canada
| | - Simon D Tran
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC, H3A 0C7, Canada.
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15
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Moradi S, Fallahi J, Tanideh N, Dara M, Aliabadi BE, Nafar S, Asadi-Yousefabad SL, Tabei SMB, Razban V. Genetically modified bone marrow mesenchymal stem cells and dental pulp mesenchymal stem cells by HIF-1alpha overexpression, differs in survival and angiogenic effects after in animal model of hind limb ischemia. GENE REPORTS 2021. [DOI: 10.1016/j.genrep.2021.101187] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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16
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Aquino JB, Sierra R, Montaldo LA. Diverse cellular origins of adult blood vascular endothelial cells. Dev Biol 2021; 477:117-132. [PMID: 34048734 DOI: 10.1016/j.ydbio.2021.05.010] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 04/26/2021] [Accepted: 05/14/2021] [Indexed: 12/11/2022]
Abstract
During embryonic stages, vascular endothelial cells (ECs) originate from the mesoderm, at specific extraembryonic and embryonic regions, through a process called vasculogenesis. In the adult, EC renewal/replacement mostly depend on local resident ECs or endothelial progenitor cells (EPCs). Nevertheless, contribution from circulating ECs/EPCs was also reported. In addition, cells lacking from EC/EPC markers with in vitro extended plasticity were shown to originate endothelial-like cells (ELCs). Most of these cells consist of mesenchymal stromal progenitors, which would eventually get mobilized from the bone marrow after injury. Based on that, current knowledge on different mouse and human bone marrow stromal cell (BM-SC) subpopulations, able to contribute with mesenchymal stromal/stem cells (MSCs), is herein reviewed. Such analyses underline an unexpected heterogeneity among sinusoidal LepR+ stromal/CAR cells. For instance, in a recent report a subgroup of LepR+ stromal/CAR progenitors, which express GLAST and is traced in Wnt1Cre;R26RTom mice, was found to contribute with ELCs in vivo. These GLAST + Wnt1+ BM-SCs were shown to get mobilized to the peripheral blood and to contribute with liver regeneration. Other sources of ELCs, such as adipose, neural and dental pulp tissues, were also published. Finally, mechanisms likely involved in the enhanced cellular plasticity properties of bone marrow/adipose tissue stromal cells, able to originate ELCs, are assessed. In the future, strategies to analyze the in vivo expression profile of stromal cells, with MSC properties, in combination with screening of active genomic regions at the single cell-level, during early postnatal development and/or after injury, will likely help understanding properties of these ELC sources.
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Affiliation(s)
- Jorge B Aquino
- CONICET-Universidad Austral, Instituto de Investigaciones en Medicina Traslacional (IIMT), Developmental Biology & Regenerative Medicine Laboratory, Argentina.
| | - Romina Sierra
- CONICET-Universidad Austral, Instituto de Investigaciones en Medicina Traslacional (IIMT), Developmental Biology & Regenerative Medicine Laboratory, Argentina
| | - Laura A Montaldo
- CONICET-Universidad Austral, Instituto de Investigaciones en Medicina Traslacional (IIMT), Developmental Biology & Regenerative Medicine Laboratory, Argentina
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17
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Huang X, Li Z, Liu A, Liu X, Guo H, Wu M, Yang X, Han B, Xuan K. Microenvironment Influences Odontogenic Mesenchymal Stem Cells Mediated Dental Pulp Regeneration. Front Physiol 2021; 12:656588. [PMID: 33967826 PMCID: PMC8100342 DOI: 10.3389/fphys.2021.656588] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 03/23/2021] [Indexed: 12/21/2022] Open
Abstract
Dental pulp as a source of nutrition for the whole tooth is vulnerable to trauma and bacterial invasion, which causes irreversible pulpitis and pulp necrosis. Dental pulp regeneration is a valuable method of restoring the viability of the dental pulp and even the whole tooth. Odontogenic mesenchymal stem cells (MSCs) residing in the dental pulp environment have been widely used in dental pulp regeneration because of their immense potential to regenerate pulp-like tissue. Furthermore, the regenerative abilities of odontogenic MSCs are easily affected by the microenvironment in which they reside. The natural environment of the dental pulp has been proven to be capable of regulating odontogenic MSC homeostasis, proliferation, and differentiation. Therefore, various approaches have been applied to mimic the natural dental pulp environment to optimize the efficacy of pulp regeneration. In addition, odontogenic MSC aggregates/spheroids similar to the natural dental pulp environment have been shown to regenerate well-organized dental pulp both in preclinical and clinical trials. In this review, we summarize recent progress in odontogenic MSC-mediated pulp regeneration and focus on the effect of the microenvironment surrounding odontogenic MSCs in the achievement of dental pulp regeneration.
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Affiliation(s)
- Xiaoyao Huang
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Zihan Li
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Anqi Liu
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Xuemei Liu
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Hao Guo
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Meiling Wu
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Xiaoxue Yang
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Bing Han
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Kun Xuan
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
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18
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Exosomes from LPS-Stimulated hDPSCs Activated the Angiogenic Potential of HUVECs In Vitro. Stem Cells Int 2021; 2021:6685307. [PMID: 33936213 PMCID: PMC8062194 DOI: 10.1155/2021/6685307] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 03/23/2021] [Accepted: 03/30/2021] [Indexed: 01/09/2023] Open
Abstract
Background Exosomes from human dental pulp stem cells (hDPSCs) were indicated to play a positive role in vascular regeneration processes. But the angiogenic capabilities of exosomes from inflammatory hDPSCs and the underlying mechanism remain unknown. In this study, the inflammatory factor lipopolysaccharide (LPS) was used to stimulate hDPSCs, and exosomes were extracted from these hDPSCs. The proangiogenic potential of exosomes was examined, and the underlying mechanism was studied. Method Exosomes were isolated from hDPSCs with or without LPS stimulation (N-EXO and LPS-EXO) and cocultured with human umbilical vein endothelial cells (HUVECs). The proangiogenic potential of exosomes was evaluated by endothelial cell proliferation, migration, and tube formation abilities in vitro. To investigate the proangiogenic mechanism of LPS-EXO, microRNA sequencing was performed to explore the microRNA profile of N-EXO and LPS-EXO. Gene Ontology (GO) analysis was used to study the functions of the predicted target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to estimate the signaling pathways associated with the inflammation-induced angiogenesis process. Result Compared to the uptake of N-EXO, uptake of LPS-EXO activated the angiogenic potential of HUVECs by promoting the proliferation, migration, and tube formation abilities in vitro. The mRNA expression levels of vascular endothelial growth factor (VEGF) and kinase-insert domain-containing receptor (KDR) in the LPS-EXO group were significantly higher than those in the N-EXO group. MicroRNA sequencing showed that 10 microRNAs were significantly changed in LPS-EXO. Pathway analysis showed that the genes targeted by differentially expressed microRNAs were involved in multiple angiogenesis-related pathways. Conclusion This study revealed that exosomes derived from inflammatory hDPSCs possessed better proangiogenic potential in vitro. This is the first time to explore the role of exosomal microRNA from hDPSCs in inflammation-induced angiogenesis. This finding sheds new light on the effect of inflammation-stimulated hDPSCs on tissue regeneration.
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19
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Mattei V, Martellucci S, Pulcini F, Santilli F, Sorice M, Delle Monache S. Regenerative Potential of DPSCs and Revascularization: Direct, Paracrine or Autocrine Effect? Stem Cell Rev Rep 2021; 17:1635-1646. [PMID: 33829353 PMCID: PMC8553678 DOI: 10.1007/s12015-021-10162-6] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/23/2021] [Indexed: 12/13/2022]
Abstract
A new source of mesenchymal stem cells has recently been discovered, the so-called dental pulp derived stem cells (DPSCs) which therefore could represent potentially tools for regenerative medicine. DPSC originate from the neural crest and are physiologically involved in dentin homeostasis; moreover, they contribute to bone remodeling and differentiation into several tissues including cartilage, bone, adipose and nervous tissues. DPSCs have also been shown to influence the angiogenesis process, for example through the release of secretory factors or by differentiating into vascular and/or perivascular cells. Angiogenesis, that has a pivotal role in tissue regeneration and repair, is defined as the formation of new vessels from preexisting vessels and is mediated by mutual and reciprocal interactions between endothelial cells and perivascular cells. It is also known that co-cultures of perivascular and endothelial cells (ECs) can form a vascular network in vitro and also in vivo. Since DPSCs seem to have characteristics similar to pericytes, understanding the possible mechanism of interaction between DPSCs and ECs during neo-angiogenesis is dramatically important for the development of advanced clinical application in the field of regeneration.
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Affiliation(s)
- Vincenzo Mattei
- Biomedicine and Advanced Technologies Rieti Center, Sabina Universitas, 02100, Rieti, Italy
- Department of Experimental Medicine, "Sapienza" University, 00161, Rome, Italy
| | - Stefano Martellucci
- Biomedicine and Advanced Technologies Rieti Center, Sabina Universitas, 02100, Rieti, Italy
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100, L'Aquila, Italy
| | - Fanny Pulcini
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100, L'Aquila, Italy
| | - Francesca Santilli
- Biomedicine and Advanced Technologies Rieti Center, Sabina Universitas, 02100, Rieti, Italy
- Department of Experimental Medicine, "Sapienza" University, 00161, Rome, Italy
| | - Maurizio Sorice
- Department of Experimental Medicine, "Sapienza" University, 00161, Rome, Italy
| | - Simona Delle Monache
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100, L'Aquila, Italy.
- StemTeCh Group, Chieti, Italy.
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20
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Angiogenesis in Regenerative Dentistry: Are We Far Enough for Therapy? Int J Mol Sci 2021; 22:ijms22020929. [PMID: 33477745 PMCID: PMC7832295 DOI: 10.3390/ijms22020929] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 01/14/2021] [Accepted: 01/15/2021] [Indexed: 12/14/2022] Open
Abstract
Angiogenesis is a broad spread term of high interest in regenerative medicine and tissue engineering including the dental field. In the last two decades, researchers worldwide struggled to find the best ways to accelerate healing, stimulate soft, and hard tissue remodeling. Stem cells, growth factors, pathways, signals, receptors, genetics are just a few words that describe this area in medicine. Dental implants, bone and soft tissue regeneration using autologous grafts, or xenografts, allografts, their integration and acceptance rely on their material properties. However, the host response, through its vascularization, plays a significant role. The present paper aims to analyze and organize the latest information about the available dental stem cells, the types of growth factors with pro-angiogenic effect and the possible therapeutic effect of enhanced angiogenesis in regenerative dentistry.
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21
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Talaat W, Aryal Ac S, Al Kawas S, Samsudin ABR, Kandile NG, Harding DRK, Ghoneim MM, Zeiada W, Jagal J, Aboelnaga A, Haider M. Nanoscale Thermosensitive Hydrogel Scaffolds Promote the Chondrogenic Differentiation of Dental Pulp Stem and Progenitor Cells: A Minimally Invasive Approach for Cartilage Regeneration. Int J Nanomedicine 2020; 15:7775-7789. [PMID: 33116500 PMCID: PMC7567564 DOI: 10.2147/ijn.s274418] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 09/16/2020] [Indexed: 12/13/2022] Open
Abstract
Purpose Several scaffolds and cell sources are being investigated for cartilage regeneration. The aim of the study was to prepare nanocellulose-based thermosensitive injectable hydrogel scaffolds and assess their potential as 3D scaffolds allowing the chondrogenic differentiation of embedded human dental pulp stem and progenitor cells (hDPSCs). Materials and Methods The hydrogel-forming solutions were prepared by adding β-glycerophosphate (GP) to chitosan (CS) at different ratios. Nanocellulose (NC) suspension was produced from hemp hurd then added dropwise to the CS/GP mixture. In vitro characterization of the prepared hydrogels involved optimizing gelation and degradation time, mass-swelling ratio, and rheological properties. The hydrogel with optimal characteristics, NC-CS/GP-21, was selected for further investigation including assessment of biocompatibility. The chondrogenesis ability of hDPSCs embedded in NC-CS/GP-21 hydrogel was investigated in vitro and compared to that of bone marrow-derived mesenchymal stem cells (BMSCs), then was confirmed in vivo in 12 adult Sprague Dawley rats. Results The selected hydrogel showed stability in culture media, had a gelation time of 2.8 minutes, showed a highly porous microstructure by scanning electron microscope, and was morphologically intact in vivo for 14 days after injection. Histological and immunohistochemical analyses and real-time PCR confirmed the chondrogenesis ability of hDPSCs embedded in NC-CS/GP-21 hydrogel. Conclusion Our results suggest that nanocellulose–chitosan thermosensitive hydrogel is a biocompatible, injectable, mechanically stable and slowly degradable scaffold. hDPSCs embedded in NC-CS/GP-21 hydrogel is a promising, minimally invasive, stem cell-based strategy for cartilage regeneration.
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Affiliation(s)
- Wael Talaat
- Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.,Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.,Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Suez Canal University, Ismaillia 41522, Egypt
| | - Smriti Aryal Ac
- Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.,Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Sausan Al Kawas
- Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.,Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - A B Rani Samsudin
- Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.,Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Nadia G Kandile
- Department of Chemistry, Faculty of Women, Ain Shams University, Heliopolis, Cairo 11757, Egypt
| | - David R K Harding
- School of Fundamental Sciences, Massey University, Palmerston North 4442, New Zealand
| | - Mohamed M Ghoneim
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Sinai University, Arish 45511, Egypt
| | - Waleed Zeiada
- Department of Civil and Environmental Engineering, College of Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates.,Public Works Engineering Department, College of Engineering, Mansoura University, Mansoura 35516, Egypt
| | - Jayalakshmi Jagal
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Ahmed Aboelnaga
- Department of Surgery, Faculty of Medicine, Suez Canal University, Ismaillia 41522, Egypt
| | - Mohamed Haider
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.,Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates.,Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 71526, Egypt
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22
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Yi B, Dissanayaka WL, Zhang C. Growth Factors and Small-molecule Compounds in Derivation of Endothelial Lineages from Dental Stem Cells. J Endod 2020; 46:S63-S70. [PMID: 32950197 DOI: 10.1016/j.joen.2020.06.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Incorporating fully assembled microvascular networks into bioengineered dental pulp constructs can significantly enhance functional blood flow and tissue survival upon transplantation. Endothelial cells (ECs), cellular building blocks of vascular tissue, play an essential role in the process of prevascularization. However, obtaining sufficient ECs from a suitable source for translational application is challenging. Dental stem cells (DSCs), which exhibit a robust proliferative ability and immunocompatibility because of their autologous origin, could be a promising alternative cell source for the derivation of endothelial lineages. Under specific culture conditions, DSCs differentiate into osteo/odontogenic, adipogenic, chondrogenic, and neurogenic cell lineages. METHODS Recently, a new approach has been developed to directly reprogram cells using chemical cocktails and growth factors. Compared with the traditional reprogramming approach based on the forced expression of exogenous transcription factors, the chemical strategy avoids the risk associated with lentiviral transduction while offering a more viable methodology to drive cell lineage switch. The aim of this review was to unveil the concept of the use of small-molecule compounds and growth factors modulating key signaling pathways to derive ECs from DSCs. RESULTS In addition, our preliminary study showed that stem cells from the apical papilla could be induced into EC-like cells using small-molecule compounds and growth factors. These EC-like cells expressed endothelial specific genes (CD31 and VEGFR2) and proteins (CD31, VEGF receptor 2, and vascular endothelial cadherin) as well as gave rise to vessel-like tubular structures in vitro. CONCLUSIONS Our preliminary results suggest that chemical reprogramming might offer a novel way to generate EC-like cells from dental stem cells.
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Affiliation(s)
- Baicheng Yi
- Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong, Special Administrative Region, China
| | - Waruna Lakmal Dissanayaka
- Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong, Special Administrative Region, China
| | - Chengfei Zhang
- Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong, Special Administrative Region, China.
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Dental Tissue-Derived Human Mesenchymal Stem Cells and Their Potential in Therapeutic Application. Stem Cells Int 2020; 2020:8864572. [PMID: 32952572 PMCID: PMC7482010 DOI: 10.1155/2020/8864572] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 07/15/2020] [Indexed: 02/05/2023] Open
Abstract
Human mesenchymal stem cells (hMSCs) are multipotent cells, which exhibit plastic adherence, express specific cell surface marker spectrum, and have multi-lineage differentiation potential. These cells can be obtained from multiple tissues. Dental tissue-derived hMSCs (dental MSCs) possess the ability to give rise to mesodermal lineage (osteocytes, adipocytes, and chondrocytes), ectodermal lineage (neurocytes), and endodermal lineages (hepatocytes). Dental MSCs were first isolated from dental pulp of the extracted third molar and till now they have been purified from various dental tissues, including pulp tissue of permanent teeth and exfoliated deciduous teeth, apical papilla, periodontal ligament, gingiva, dental follicle, tooth germ, and alveolar bone. Dental MSCs are not only easily accessible but are also expandable in vitro with relative genomic stability for a long period of time. Moreover, dental MSCs have exhibited immunomodulatory properties by secreting cytokines. Easy accessibility, multi-lineage differentiation potential, and immunomodulatory effects make dental MSCs distinct from the other hMSCs and an effective tool in stem cell-based therapy. Several preclinical studies and clinical trials have been performed using dental MSCs in the treatment of multiple ailments, ranging from dental diseases to nondental diseases. The present review has summarized dental MSC sources, multi-lineage differentiation capacities, immunomodulatory features, its potential in the treatment of diseases, and its application in both preclinical studies and clinical trials. The regenerative therapeutic strategies in dental medicine have also been discussed.
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Sui B, Wu D, Xiang L, Fu Y, Kou X, Shi S. Dental Pulp Stem Cells: From Discovery to Clinical Application. J Endod 2020; 46:S46-S55. [DOI: 10.1016/j.joen.2020.06.027] [Citation(s) in RCA: 88] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Zayed M, Iohara K. Immunomodulation and Regeneration Properties of Dental Pulp Stem Cells: A Potential Therapy to Treat Coronavirus Disease 2019. Cell Transplant 2020; 29:963689720952089. [PMID: 32830527 PMCID: PMC7443577 DOI: 10.1177/0963689720952089] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic, originating from Wuhan, China, is known to cause severe acute respiratory symptoms. The occurrence of a cytokine storm in the lungs is a critical step in the disease pathogenesis, as it causes pathological lesions, pulmonary edema, and acute respiratory distress syndrome, potentially resulting in death. Currently, there is no effective treatment that targets the cytokine storm and helps regenerate the damaged tissue. Mesenchymal stem cells (MSCs) are known to act as anti-inflammatory/immunomodulatory candidates and activate endogenous regeneration. As a result, MSC therapy is a potential treatment approach for COVID-19. Intravenous injection of clinical-grade MSCs into COVID-19 patients can induce an immunomodulatory response along with improved lung function. Dental pulp stem cells (DPSCs) are considered a potential source of MSCs for immunomodulation, tissue regeneration, and clinical application. Although some current clinical trials have treated COVID-19 patients with DPSCs, this therapy has not been approved. Here, we review the potential use of DPSCs and their significance in the development of a therapy for COVID-19.
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Affiliation(s)
- Mohammed Zayed
- Department of Stem Cell Biology and Regenerative Medicine, National Center for Geriatrics and Gerontology, Research Institute, Obu, Aichi, Japan
- Department of Surgery, College of Veterinary Medicine, South Valley University, Qena, Egypt
- Mohammed Zayed, Department of Stem Cell Biology and Regenerative Medicine, National Center for Geriatrics and Gerontology, Research Institute, Obu, Aichi 474-8511, Japan.
| | - Koichiro Iohara
- Department of Stem Cell Biology and Regenerative Medicine, National Center for Geriatrics and Gerontology, Research Institute, Obu, Aichi, Japan
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Yoshida S, Tomokiyo A, Hasegawa D, Hamano S, Sugii H, Maeda H. Insight into the Role of Dental Pulp Stem Cells in Regenerative Therapy. BIOLOGY 2020; 9:biology9070160. [PMID: 32659896 PMCID: PMC7407391 DOI: 10.3390/biology9070160] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 07/02/2020] [Accepted: 07/05/2020] [Indexed: 02/07/2023]
Abstract
Mesenchymal stem cells (MSCs) have the capacity for self-renewal and multilineage differentiation potential, and are considered a promising cell population for cell-based therapy and tissue regeneration. MSCs are isolated from various organs including dental pulp, which originates from cranial neural crest-derived ectomesenchyme. Recently, dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs) have been isolated from dental pulp tissue of adult permanent teeth and deciduous teeth, respectively. Because of their MSC-like characteristics such as high growth capacity, multipotency, expression of MSC-related markers, and immunomodulatory effects, they are suggested to be an important cell source for tissue regeneration. Here, we review the features of these cells, their potential to regenerate damaged tissues, and the recently acquired understanding of their potential for clinical application in regenerative medicine.
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Affiliation(s)
- Shinichiro Yoshida
- Department of Endodontology, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; (A.T.); (D.H.); (H.S.); (H.M.)
- Correspondence: ; Tel.: +81-92-642-6432
| | - Atsushi Tomokiyo
- Department of Endodontology, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; (A.T.); (D.H.); (H.S.); (H.M.)
| | - Daigaku Hasegawa
- Department of Endodontology, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; (A.T.); (D.H.); (H.S.); (H.M.)
| | - Sayuri Hamano
- OBT Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan;
- Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Hideki Sugii
- Department of Endodontology, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; (A.T.); (D.H.); (H.S.); (H.M.)
| | - Hidefumi Maeda
- Department of Endodontology, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; (A.T.); (D.H.); (H.S.); (H.M.)
- Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
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Differential expression of long noncoding RNAs from dental pulp stem cells in the microenvironment of the angiogenesis. Arch Oral Biol 2020; 113:104691. [PMID: 32247880 DOI: 10.1016/j.archoralbio.2020.104691] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Revised: 01/28/2020] [Accepted: 03/02/2020] [Indexed: 01/04/2023]
Abstract
INTRODUCTION Angiogenesis is important in pulp-dentin formation. Among the regulatory factors, long noncoding RNA (LncRNA) is a class of functional RNA molecules that are not translated into protein and involved in regulating multiple physiological processes. The different expression of LncRNA and its target gene in dental pulp stem cells (DPSCs) were explored and may provide a theoretical basis for future regulation of dental pulp angiogenesis. METHODS In this study, we cultured DPSCs from healthy dental pulp tissues and divided them into two groups: the normal DPSCs and the DPSCs cultured in vascular induction medium. In total, 40,173 LncRNA probes and 20,730 protein coding mRNAs were detected through microarray, which were then verified by the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) method. RESULTS The result of differential expressions measured in LncRNA through microarray showed that 376 LncRNAs increased significantly and 426 were downregulated among the two groups of cells. Moreover, the mRNA microarray in normal cultured DPSCs showed that 629 LncRNAs were significantly upregulated, while 529 of them were downregulated compared with the DPSCs that were cultured in vascular induction medium. Gene ontology (GO) analysis inferred the molecular function of mRNAs. Pathway analysis showed that 52 signaling pathways were involved in the differentiation process of DPSCs. qRT-PCR analysis, conducted for validation, showed results consistent with the microarray analysis. CONCLUSIONS We found that a number of different regulators are involved in inducing vascular differentiation of DPSCs, which provides a foundation for subsequent experiments.
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El Moshy S, Radwan IA, Rady D, Abbass MMS, El-Rashidy AA, Sadek KM, Dörfer CE, Fawzy El-Sayed KM. Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications. Stem Cells Int 2020; 2020:7593402. [PMID: 32089709 PMCID: PMC7013327 DOI: 10.1155/2020/7593402] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Revised: 12/23/2019] [Accepted: 01/10/2020] [Indexed: 12/13/2022] Open
Abstract
Regenerative medicine literature has proposed mesenchymal stem/progenitor cell- (MSC-) mediated therapeutic approaches for their great potential in managing various diseases and tissue defects. Dental MSCs represent promising alternatives to nondental MSCs, owing to their ease of harvesting with minimally invasive procedures. Their mechanism of action has been attributed to their cell-to-cell contacts as well as to the paracrine effect of their secreted factors, namely, secretome. In this context, dental MSC-derived secretome/conditioned medium could represent a unique cell-free regenerative and therapeutic approach, with fascinating advantages over parent cells. This article reviews the application of different populations of dental MSC secretome/conditioned medium in in vitro and in vivo animal models, highlights their significant implementation in treating different tissue' diseases, and clarifies the significant bioactive molecules involved in their regenerative potential. The analysis of these recent studies clearly indicate that dental MSCs' secretome/conditioned medium could be effective in treating neural injuries, for dental tissue regeneration, in repairing bone defects, and in managing cardiovascular diseases, diabetes mellitus, hepatic regeneration, and skin injuries, through regulating anti-inflammatory, antiapoptotic, angiogenic, osteogenic, and neurogenic mediators.
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Affiliation(s)
- Sara El Moshy
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Israa Ahmed Radwan
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Dina Rady
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Marwa M. S. Abbass
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Aiah A. El-Rashidy
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Biomaterials Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Khadiga M. Sadek
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Biomaterials Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Christof E. Dörfer
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
| | - Karim M. Fawzy El-Sayed
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
- Oral Medicine and Periodontology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
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Fernandes TL, Cortez de SantAnna JP, Frisene I, Gazarini JP, Gomes Pinheiro CC, Gomoll AH, Lattermann C, Hernandez AJ, Franco Bueno D. Systematic Review of Human Dental Pulp Stem Cells for Cartilage Regeneration. TISSUE ENGINEERING PART B-REVIEWS 2020; 26:1-12. [PMID: 31744404 DOI: 10.1089/ten.teb.2019.0140] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Background: Symptomatic cartilage lesions and early osteoarthritis produce significant clinical and economic burdens. Cartilage repair can improve the symptoms and delay arthroplasty. The complete healing of damaged cartilage with the consistent reproduction of normal hyaline cartilage has not yet been achieved. The choice of harvesting site might influence the cells' abilities to modulate immunologic and inflammatory responses. Recently, dental pulp has been shown to contain a stem cell niche consisting of dental pulp stem cells (DPSCs) that maintain their self-renewal capacity due to the active environment in the dental pulp of deciduous teeth. Objective: The aim of this study was to critically review the current literature on the potential and limitations of the use of dental pulp-derived mesenchymal stem cells in cell-based therapies for cartilage regeneration. Methods: An electronic, customized search of scientific articles was conducted using the PubMed/MEDLINE and EMBASE databases from their inception to December 2018. The inclusion criteria were applied, and the articles that described the use of DPSC in cartilage treatment were selected for complete evaluation. The articles were classified according to the scaffold used, experimental model, chondrogenic differentiation features, defect location, cartilage evaluation, and results. After the application of the eligibility criteria, a total of nine studies were selected and fully analyzed. Results: A variety of animal models were used, including mice, rats, rabbits, and miniature pigs, to evaluate the quality and safety of human DPSCs in the repair of cartilage defects. Among the articles, two studies focused on preclinical models of cartilage tissue engineering. Five studies implanted DPSCs in other animal sites. Conclusion: The use of DPSCs is a potential new stem cell therapy for articular cartilage repair. The preclinical evidence discussed in this article provides a solid foundation for future clinical trials. Impact statement Osteoarthritis presents an ever-increasing clinical and socioeconomic burden. While cartilage repair has the potential to improve symptoms and delay joint replacement, complete regeneration of hyaline cartilage has been an elusive goal. Dental pulp has been shown to contain a niche that protects dental pulp stem cells (DPSCs) from the cumulative effects of genetic and environmental factors and maintains their self-renewal capacity due to the active environment. Transplantation and preclinical trials have demonstrated the strong potential of regenerative tissue-engineering protocols using DPSCs.
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Affiliation(s)
- Tiago Lazzaretti Fernandes
- Sports Medicine Division, Institute of Orthopedics and Traumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.,Hospital Sírio-Libanês, São Paulo, Brazil.,Department of Orthopedic Surgery, Center for Cartilage Repair and Sports Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - João Paulo Cortez de SantAnna
- Sports Medicine Division, Institute of Orthopedics and Traumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Igor Frisene
- Sports Medicine Division, Institute of Orthopedics and Traumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - João Paulo Gazarini
- Sports Medicine Division, Institute of Orthopedics and Traumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | | | | | - Christian Lattermann
- Department of Orthopedic Surgery, Center for Cartilage Repair and Sports Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Arnaldo Jose Hernandez
- Sports Medicine Division, Institute of Orthopedics and Traumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.,Hospital Sírio-Libanês, São Paulo, Brazil
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Fawzy El-Sayed KM, Elsalawy R, Ibrahim N, Gadalla M, Albargasy H, Zahra N, Mokhtar S, El Nahhas N, El Kaliouby Y, Dörfer CE. The Dental Pulp Stem/Progenitor Cells-Mediated Inflammatory-Regenerative Axis. TISSUE ENGINEERING PART B-REVIEWS 2019; 25:445-460. [DOI: 10.1089/ten.teb.2019.0106] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Karim M. Fawzy El-Sayed
- Oral Medicine and Periodontology Department, Faculty of Oral and Dental Medicine, Cairo University, Cairo, Egypt
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
| | | | | | | | | | - Nehal Zahra
- Faculty of Dentistry, New Giza University, Giza, Egypt
| | | | | | | | - Christof E. Dörfer
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
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Electrical Stimulation through Conductive Substrate to Enhance Osteo-Differentiation of Human Dental Pulp-Derived Stem Cells. APPLIED SCIENCES-BASEL 2019. [DOI: 10.3390/app9183938] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Human dental pulp-derived stem cells (hDPSCs) are promising cellular sources for bone healing. The acceleration of their differentiation should be beneficial to their clinical application. Therefore, a conductive polypyrrole (PPy)-made electrical stimulation (ES) device was fabricated to provide direct-current electric field (DCEF) treatment, and its effect on osteo-differentiation of hDPSCs was investigated in this study. To determine the optimal treating time, electrical field of 0.33 V/cm was applied to hDPSCs once for 4 h on different days after the osteo-induction. The alizarin red S staining results suggested that ES accelerated the mineralization rates of hDPSCs. The quantification analysis results revealed a nearly threefold enhancement in calcium deposition by ES at day 0, 2, and 4, whereas the promotion effect in later stages was in vain. To determine the ES-mediated signaling pathway, the expression of genes in the bone morphogenetic protein (BMP) family and related receptors were quantified using qPCR. In the early stages of osteo-differentiation, the mRNA levels of BMP2, BMP3, BMP4, and BMP5 were increased significantly in the ES groups, indicating that these genes were involved in the specific signaling routes induced by ES. We are the first using DCEF to improve the osteo-differentiation of hDPSCs, and our results promise the therapeutic applications of hDPSCs on cell-based bone tissue engineering.
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Novais A, Lesieur J, Sadoine J, Slimani L, Baroukh B, Saubaméa B, Schmitt A, Vital S, Poliard A, Hélary C, Rochefort GY, Chaussain C, Gorin C. Priming Dental Pulp Stem Cells from Human Exfoliated Deciduous Teeth with Fibroblast Growth Factor-2 Enhances Mineralization Within Tissue-Engineered Constructs Implanted in Craniofacial Bone Defects. Stem Cells Transl Med 2019; 8:844-857. [PMID: 31016898 PMCID: PMC6646701 DOI: 10.1002/sctm.18-0182] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 12/03/2018] [Indexed: 12/17/2022] Open
Abstract
The craniofacial area is prone to trauma or pathologies often resulting in large bone damages. One potential treatment option is the grafting of a tissue-engineered construct seeded with adult mesenchymal stem cells (MSCs). The dental pulp appears as a relevant source of MSCs, as dental pulp stem cells display strong osteogenic properties and are efficient at bone formation and repair. Fibroblast growth factor-2 (FGF-2) and/or hypoxia primings were shown to boost the angiogenesis potential of dental pulp stem cells from human exfoliated deciduous teeth (SHED). Based on these findings, we hypothesized here that these primings would also improve bone formation in the context of craniofacial bone repair. We found that both hypoxic and FGF-2 primings enhanced SHED proliferation and osteogenic differentiation into plastically compressed collagen hydrogels, with a much stronger effect observed with the FGF-2 priming. After implantation in immunodeficient mice, the tissue-engineered constructs seeded with FGF-2 primed SHED mediated faster intramembranous bone formation into critical size calvarial defects than the other groups (no priming and hypoxia priming). The results of this study highlight the interest of FGF-2 priming in tissue engineering for craniofacial bone repair. Stem Cells Translational Medicine 2019;8:844&857.
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Affiliation(s)
- Anita Novais
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
- AP‐HP Département d'OdontologieHôpitaux Universitaires PNVS, Charles Foix et Henri MondorIle de FranceFrance
| | - Julie Lesieur
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
| | - Jérémy Sadoine
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
| | - Lotfi Slimani
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
| | - Brigitte Baroukh
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
| | - Bruno Saubaméa
- Cellular and Molecular Imaging FacilityInserm US25, CNRS UMS 3612, Faculté de Pharmacie de Paris, Université Paris Descartes Sorbonne Paris CitéParisFrance
| | - Alain Schmitt
- Cochin Institute, Transmission Electron Microscopy Platform, INSERM U1016, CNRS UMR8104Université Paris Descartes Sorbonne Paris CitéParisFrance
| | - Sibylle Vital
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
- AP‐HP Département d'OdontologieHôpitaux Universitaires PNVS, Charles Foix et Henri MondorIle de FranceFrance
| | - Anne Poliard
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
| | - Christophe Hélary
- Laboratoire de Chimie de la Matière Condensée de ParisSorbonne Universités, CNRS, Collège de FranceParisFrance
| | - Gaël Y. Rochefort
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
| | - Catherine Chaussain
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
- AP‐HP Département d'OdontologieHôpitaux Universitaires PNVS, Charles Foix et Henri MondorIle de FranceFrance
| | - Caroline Gorin
- EA 2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant (PIV)Dental School, Université Paris Descartes Sorbonne Paris CitéMontrougeFrance
- AP‐HP Département d'OdontologieHôpitaux Universitaires PNVS, Charles Foix et Henri MondorIle de FranceFrance
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3D Human Periodontal Stem Cells and Endothelial Cells Promote Bone Development in Bovine Pericardium-Based Tissue Biomaterial. MATERIALS 2019; 12:ma12132157. [PMID: 31284396 PMCID: PMC6651787 DOI: 10.3390/ma12132157] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 06/24/2019] [Accepted: 06/30/2019] [Indexed: 12/20/2022]
Abstract
Bone defects repair represents a public and urgent problem in clinical practice, in fact, every year, more than two million patients required new treatments for bone injuries. Today a complete vascularization is strategic in bone formation, representing a new frontier for clinical application. Aim of this research has been developed a three-dimensional (3D) coculture platform using a bovine pericardium collagen membrane (BioR) loaded with human periodontal ligament stem cells (hPDLSCs) and endothelial differentiated cells from hPDLSCs (E-hPDLSCs) able to undergo toward osteoangiogenesis differentiation process. First, we have characterized at confocal laser scanning microscopy (CLSM) level the E-hPDLSCs phenotype profile, through CD31 and CD34 markers expression and the ability to tube vessel formation. Real Time-Polimerase Chain Reaction (RT-PCR) and western blotting analyses revealed the upregulation of Runt-related transcription factor 2 (RUNX2), Collagen 1A1 (COL1A1), Vascular Endothelial Growth Factor-A (VEGF-A) genes and proteins in the living construct composed by hPDLSCs + E-hPDSCs/BioR. Human PDLSCs + E-hPDLSCs/BioR construct showed also an enhacement of de novo synthesis of osteocalcin. Given that, the extracellular-signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) transduction signaling was involved in the osteogenesis and angiogenesis process, the ERK1/2 protein level at biochemical level, in our experimental model, has been investigated. Our results evidenced an upregulation of ERK1/2 proteins level born in the living construct. In conclusion, we believe that the use of the hPDLSCs and E-hPDLSCs coculture togheter with BioR as substrate, could represent an efficient model able to activate through ERK1/2 signaling pathway the osteoangiogenesis process, and then representing a new potential engineered platform for surgeons during the repair and the healing of bone defects.
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Liu L, Leng S, Yue J, Lu Q, Xu W, Yi X, Huang D, Zhang L. EDTA Enhances Stromal Cell–derived Factor 1α–induced Migration of Dental Pulp Cells by Up-regulating Chemokine Receptor 4 Expression. J Endod 2019; 45:599-605.e1. [DOI: 10.1016/j.joen.2019.01.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 12/12/2018] [Accepted: 01/08/2019] [Indexed: 12/18/2022]
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Nakashima M, Iohara K, Bottino MC, Fouad AF, Nör JE, Huang GTJ. Animal Models for Stem Cell-Based Pulp Regeneration: Foundation for Human Clinical Applications. TISSUE ENGINEERING. PART B, REVIEWS 2019; 25:100-113. [PMID: 30284967 PMCID: PMC6486672 DOI: 10.1089/ten.teb.2018.0194] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 09/18/2018] [Indexed: 12/21/2022]
Abstract
IMPACT STATEMENT Animal models are essential for tissue regeneration studies. This review summarizes and discusses the small and large animal models, including mouse, ferret, dog, and miniswine that have been utilized to experiment and to demonstrate stem cell-mediated dental pulp tissue regeneration. We describe the models based on the location where the tissue regeneration is tested-either ectopic, semiorthotopic, or orthotopic. Developing and utilizing optimal animal models for both mechanistic and translational studies of pulp regeneration are of critical importance to advance this field.
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Affiliation(s)
- Misako Nakashima
- Department of Stem Cell Biology and Regenerative Medicine, National Center for Geriatrics and Gerontology, Aichi, Japan
| | - Koichiro Iohara
- Department of Stem Cell Biology and Regenerative Medicine, National Center for Geriatrics and Gerontology, Aichi, Japan
| | - Marco C. Bottino
- Department of Cariology, Restorative Sciences, Endodontics, University of Michigan, School of Dentistry, Ann Arbor, Michigan
| | - Ashraf F. Fouad
- Department of Endodontics, School of Dentistry, University of North Carolina, Chapel Hill, North Carolina
| | - Jacques E. Nör
- Department of Cariology, Restorative Sciences, Endodontics, University of Michigan, School of Dentistry, Ann Arbor, Michigan
| | - George T.-J. Huang
- Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, Tennessee
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Clinical Potential and Current Progress of Dental Pulp Stem Cells for Various Systemic Diseases in Regenerative Medicine: A Concise Review. Int J Mol Sci 2019; 20:ijms20051132. [PMID: 30845639 PMCID: PMC6429131 DOI: 10.3390/ijms20051132] [Citation(s) in RCA: 157] [Impact Index Per Article: 26.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Revised: 02/28/2019] [Accepted: 03/01/2019] [Indexed: 12/13/2022] Open
Abstract
Dental pulp stem cells (DPSCs) are mesenchymal stem cells (MSCs) that have multipotent differentiation and a self-renewal ability. They have been useful not only for dental diseases, but also for systemic diseases. Extensive studies have suggested that DPSCs are effective for various diseases, such as spinal cord injuries, Parkinson's disease, Alzheimer's disease, cerebral ischemia, myocardial infarction, muscular dystrophy, diabetes, liver diseases, eye diseases, immune diseases, and oral diseases. DPSCs have the potential for use in a cell-therapeutic paradigm shift to treat these diseases. It has also been reported that DPSCs have higher regenerative potential than the bone marrow-derived mesenchymal stem cells known as representative MSCs. Therefore, DPSCs have recently gathered much attention. In this review, the therapeutic potential of DPSCs, the latest progress in the pre-clinical study for treatment of these various systemic diseases, and the clinical applications of DPSCs in regenerative medicine, are all summarized. Although challenges, including mechanisms of the effects and establishment of cell processing and transplantation methods for clinical use, still remain, DPSCs could be promising stem cells sources for various clinical applications, because of their easy isolation by a noninvasive procedure without ethical concerns.
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Chmilewsky F, Liang R, Kanazawa M, About I, Cooper LF, George A. C5L2 Regulates DMP1 Expression during Odontoblastic Differentiation. J Dent Res 2019; 98:597-604. [PMID: 30702959 DOI: 10.1177/0022034518820461] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The presence of stem cells within the dental-pulp tissue as well as their differentiation into a new generation of functional odontoblast-like cells constitutes an important step of the dentin-pulp regeneration. Recent investigations demonstrated that the complement system activation participates in 2 critical steps of dentin-pulp regeneration: pulp progenitor's recruitment and pulp nerve sprouting. Surprisingly, its implication in odontoblastic differentiation has not been addressed yet. Since the complement receptor C5a receptor-like 2 (C5L2) is expressed by different stem cells, the aim of this study is to investigate if the dental pulp stem cells express C5L2 and if this receptor participates in odontoblastic differentiation. Immunohistochemistry performed on human third molar pulp sections showed a perivascular co-localization of the mesenchymal stem cell markers STRO1 and C5L2. In vitro immunofluorescent staining confirmed that hDPSCs express C5L2. Furthermore, we determined by real-time polymerase chain reaction that the expression of C5L2 is highly modulated in human dental pulp stem cells (hDPSCs) undergoing odontoblastic differentiation. Moreover, we showed that this odontogenesis-regulated expression of C5L2 is specifically potentiated by the proinflammatory cytokine TNFα. Using a C5L2-siRNA silencing strategy, we provide direct evidence that C5L2 constitutes a negative regulator of the dentinogenic marker DMP1 (dentin matrix protein 1) expression by hDPSCs. Our findings suggest a direct correlation between the odontoblastic differentiation and the level of C5L2 expression in hDPSCs and identify C5L2 as a negative regulator of DMP1 expression by hDPSCs during the odontoblastic differentiation and inflammation processes. This work is the first to demonstrate the involvement of C5L2 in the biological function of stem cells, provides an important knowledge in understanding odontoblastic differentiation of dental pulp stem cells, and may be useful in future dentin-pulp engineering strategies.
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Affiliation(s)
- F Chmilewsky
- 1 Department of Oral Biology, University of Illinois at Chicago, Chicago, IL, USA
| | - R Liang
- 1 Department of Oral Biology, University of Illinois at Chicago, Chicago, IL, USA
| | - M Kanazawa
- 1 Department of Oral Biology, University of Illinois at Chicago, Chicago, IL, USA
| | - I About
- 2 Department of Oral Biology, Aix Marseille Université, Marseille, France
| | - L F Cooper
- 1 Department of Oral Biology, University of Illinois at Chicago, Chicago, IL, USA
| | - A George
- 1 Department of Oral Biology, University of Illinois at Chicago, Chicago, IL, USA
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Al-Habib M, Huang GTJ. Dental Mesenchymal Stem Cells: Dental Pulp Stem Cells, Periodontal Ligament Stem Cells, Apical Papilla Stem Cells, and Primary Teeth Stem Cells-Isolation, Characterization, and Expansion for Tissue Engineering. Methods Mol Biol 2019; 1922:59-76. [PMID: 30838565 DOI: 10.1007/978-1-4939-9012-2_7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Dental stem cells (DSCs) have been shown to possess great potential for multiple biomedical applications, especially for dental tissue regeneration. They are a special type of subpopulation of mesenchymal stem/stromal cells (MSCs) and present subtle differences from other types of MSCs. Therefore, it requires a specialized expertise to isolate, culture, and characterize these cells in vitro and in vivo. The purpose of this chapter is to share our experience in studying these cells. We will describe in detail laboratory protocols outlining how the cells are isolated, cultured, expanded, and characterized using various in vitro cellular and biochemical analyses, as well as an in vivo study model using immunocompromised mice to observe tissue regeneration after transplantation of these DSCs.
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Affiliation(s)
- Mey Al-Habib
- Faculty of Dentistry, Department of Endodontics, King Abdulaziz University, Jeddah, Saudi Arabia
| | - George T-J Huang
- Department of Bioscience Research, University of Tennessee Health Science Center, College of Dentistry, Memphis, TN, USA.
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Sui B, Chen C, Kou X, Li B, Xuan K, Shi S, Jin Y. Pulp Stem Cell-Mediated Functional Pulp Regeneration. J Dent Res 2019; 98:27-35. [PMID: 30372659 DOI: 10.1177/0022034518808754] [Citation(s) in RCA: 100] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The preservation of vital dental pulp with vasculature and nerve components remains one of the most significant challenges in modern dentistry. Due to the immense potential for neurovascularization, mesenchymal stem cell (MSC) transplantation has shown emerging promise in regenerative medicine and dental translational practice. Actually, pulp mesenchymal stem cells, including postnatal dental pulp stem cells (from permanent teeth) and stem cells from human exfoliated deciduous teeth, possess unique properties based on their origins from neural crest or glial cells. Furthermore, they reside in a neurovascular niche and have the potential for neurogenesis, angiogenesis, and neurovascular inductive activity. According to current pulp regeneration strategies, pulp stem cell-mediated approaches to regeneration have demonstrated convincing evidence that they can rebuild the complex histologic structure of native pulp in situ with highly organized physiologic patterns or even achieve de novo regeneration of complete dental pulp tissues. More importantly, recent clinical studies emphasized in situ neurovascularization outcomes in successful regeneration of vitalized pulp via pulp stem cell transplantation. In this review, we summarize recent breakthroughs in pulp stem cell-mediated pulp regeneration, emphasizing the crucial achievement of neurovascularization. This functional pulp regeneration represents an innovative and promising approach for future regenerative endodontics.
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Affiliation(s)
- B Sui
- 1 State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, China
- 2 Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - C Chen
- 2 Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - X Kou
- 2 Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
- 3 Guanghua School of Stomatology, South China Center of Craniofacial Stem Cell Research, Sun Yat-sen University, Guangzhou, China
| | - B Li
- 1 State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - K Xuan
- 1 State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - S Shi
- 2 Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
- 3 Guanghua School of Stomatology, South China Center of Craniofacial Stem Cell Research, Sun Yat-sen University, Guangzhou, China
| | - Y Jin
- 1 State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, China
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Hilkens P, Lambrichts I, Bronckaers A. Current and Future Views on Pulpal Angiogenesis. CLINICAL APPROACHES IN ENDODONTIC REGENERATION 2019:37-53. [DOI: 10.1007/978-3-319-96848-3_3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Tissue Engineering of Necrotic Dental Pulp of Immature Teeth with Apical Periodontitis in Dogs: Radiographic and Histological Evaluation. J Clin Pediatr Dent 2018; 42:373-382. [PMID: 29763345 DOI: 10.17796/1053-4625-42.5.9] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
AIM To evaluate tissue engineering technology to regenerate pulp-dentin like tissues in pulp canals of immature necrotic permanent teeth with apical periodontitis in dogs. STUDY DESIGN The study was performed on 36 teeth in 12 dogs. The experiment was carried out using split mouth design. In each dog 3 teeth were selected for implementing the study procedure. Apical periodontitis was induced in Group A and B teeth. Group (A): immature upper left 2nd permanent incisors that were transplanted with a construct of autologous dental pulp stem cells with growth factors seeded in a chitosn hydrogel scaffold. Group (B): immature upper right 2nd permanent incisor that received only growth factors with scaffold. A third tooth in each dog was selected randomly for isolation of dental pulp stem cells (DPSCs). Both groups were closed with a double coronal seal of white MTA (Mineral trioxide aggregate) and glass ionomer cement. Both groups were monitored radiographically for 4 months and histologically after sacrificing the animals. RESULTS There was no statistically significant difference in radiographic findings between group (A) and group (B) for healing of radiolucencies, while there was statistically significant difference between group (A) and group (B) regarding radicular thickening, root lengthening and apical closure. Histologically, group (A) teeth showed regeneration of pulp- dentin like tissue while group (B) teeth did not show any tissue regeneration. CONCLUSION Dental pulp stem cells and growth factors incorporated in chitosan hydrogel are able to regenerate pulp- dentine like tissue and help in complete root maturation of non-vital immature permanent teeth with apical periodontitis in dogs.
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Commitment of Oral-Derived Stem Cells in Dental and Maxillofacial Applications. Dent J (Basel) 2018; 6:dj6040072. [PMID: 30551556 PMCID: PMC6313393 DOI: 10.3390/dj6040072] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 11/30/2018] [Accepted: 12/11/2018] [Indexed: 12/16/2022] Open
Abstract
Tissue engineering is based on the interaction between stem cells, biomaterials and factors delivered in biological niches. Oral tissues have been found to be rich in stem cells from different sources: Stem cells from oral cavity are easily harvestable and have shown a great plasticity towards the main lineages, specifically towards bone tissues. Dental pulp stem cells (DPSCs) are the most investigated mesenchymal stem cells (MSCs) from dental tissues, however, the oral cavity hosts several other stem cell lineages that have also been reported to be a good alternative in bone tissue engineering. In particular, the newly discovered population of mesenchymal stem cells derived from human periapical inflamed cysts (hPCy-MSCs) have showed very promising properties, including high plasticity toward bone, vascular and neural phenotypes. In this topical review, the authors described the main oral-derived stem cell populations, their most interesting characteristics and their ability towards osteogenic lineage. This review has also investigated the main clinical procedures, reported in the recent literature, involving oral derived-MSCs and biomaterials to get better bone regeneration in dental procedures. The numerous populations of mesenchymal stem cells isolated from oral tissues (DPSCs, SHEDs, PDLSCs, DFSCs, SCAPs, hPCy-MSCs) retain proliferation ability and multipotency; these features are exploited for clinical purposes, including regeneration of injured tissues and local immunomodulation; we reported on the last studies on the proper use of such MSCs within a biological niche and the proper way to storage them for future clinical use.
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Insights into Endothelial Progenitor Cells: Origin, Classification, Potentials, and Prospects. Stem Cells Int 2018; 2018:9847015. [PMID: 30581475 PMCID: PMC6276490 DOI: 10.1155/2018/9847015] [Citation(s) in RCA: 134] [Impact Index Per Article: 19.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Revised: 08/27/2018] [Accepted: 09/18/2018] [Indexed: 02/07/2023] Open
Abstract
With the discovery of endothelial progenitor cells (EPCs) in the late 1990s, a paradigm shift in the concept of neoangiogenesis occurred. The identification of circulating EPCs in peripheral blood marked the beginning of a new era with enormous potential in the rapidly transforming regenerative field. Overwhelmed with the revelation, researchers across the globe focused on isolating, defining, and interpreting the role of EPCs in various physiological and pathological conditions. Consequently, controversies emerged regarding the isolation techniques and classification of EPCs. Nevertheless, the potential of using EPCs in tissue engineering as an angiogenic source has been extensively explored. Concomitantly, the impact of EPCs on various diseases, such as diabetes, cancer, and cardiovascular diseases, has been studied. Within the limitations of the current knowledge, this review attempts to delineate the concept of EPCs in a sequential manner from the speculative history to a definitive presence (origin, sources of EPCs, isolation, and identification) and significance of these EPCs. Additionally, this review is aimed at serving as a guide for investigators, identifying potential research gaps, and summarizing our current and future prospects regarding EPCs.
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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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Raza SS, Wagner AP, Hussain YS, Khan MA. Mechanisms underlying dental-derived stem cell-mediated neurorestoration in neurodegenerative disorders. Stem Cell Res Ther 2018; 9:245. [PMID: 30257724 PMCID: PMC6158826 DOI: 10.1186/s13287-018-1005-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Neurodegenerative disorders have a complex pathology and are characterized by a progressive loss of neuronal architecture in the brain or spinal cord. Neuroprotective agents have demonstrated promising results at the preclinical stage, but this has not been confirmed at the clinical stage. Thus far, no neuroprotective drug that can prevent neuronal degeneration in patients with neurodegenerative disorders is available. MAIN BODY Recent studies have focused on neurorestorative measures, such as cell-based therapy, rather than neuroprotective treatment. The utility of cell-based approaches for the treatment of neurodegenerative disorders has been explored extensively, and the results have been somewhat promising with regard to reversing the outcome. Because of their neural crest origin, ease of harvest, accessibility, ethical suitability, and potential to differentiate into the neurogenic lineage, dental-derived stem cells (DSCs) have become an attractive source for cell-based neurorestoration therapies. In the present review, we summarize the possible use of DSC-based neurorestoration therapy as an alternative treatment for neurodegenerative disorders, with a particular emphasis on the mechanism underlying recovery in neurodegenerative disorders. CONCLUSION Transplantation research in neurodegenerative diseases should aim to understand the mechanism providing benefits both at the molecular and functional level. Due to their ease of accessibility, plasticity, and ethical suitability, DSCs hold promise to overcome the existing challenges in the field of neurodegeneration through multiple mechanisms, such as cell replacement, bystander effect, vasculogenesis, synaptogenesis, immunomodulation, and by inhibiting apoptosis.
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Affiliation(s)
- Syed Shadab Raza
- Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era Medical College & Hospital, Era University, Lucknow, Uttar Pradesh, 226003, India. .,Department of Stem Cell Biology and Regenerative Medicine, Era University, Lucknow, 226003, India.
| | - Aurel Popa Wagner
- Departmentof Dental Materials, RUHS College of Dental Sciences, Subhash Nagar, Jaipur, Rajasthan, 302002, India.,Center of Clinical and Experimental Medicine, University of Medicine and Pharmacy Craiova, Craiova, Romania.,School of Medicine, Griffith University, Southport, QLD, Australia
| | - Yawer S Hussain
- Department of Neurology, Chair of Vascular Neurology and Dementia, Essen University Hospital, Essen, Germany
| | - Mohsin Ali Khan
- Era Medical College & Hospital, Era University, Lucknow, Uttar Pradesh, 226003, India
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Baniebrahimi G, Khanmohammadi R, Mir F. Teeth-derived stem cells: A source for cell therapy. J Cell Physiol 2018; 234:2426-2435. [PMID: 30238990 DOI: 10.1002/jcp.27270] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Accepted: 07/26/2018] [Indexed: 12/12/2022]
Abstract
Cell therapy is one of the important therapeutic approaches in the treatment of many diseases such as cancer, degenerative diseases, and cardiovascular diseases. Among various cell types, which could be used as cell therapies, stem cell therapy has emerged as powerful tools in the treatment of several diseases. Multipotent stem cells are one of the main classes of stem cells that could originate from different parts of the body such as bone marrow, adipose, placenta, and tooth. Among several types of multipotent stem cells, tooth-derived stem cells (TDSCs) are associated with special properties such as accessible, easy isolation, and low invasive, which have introduced them as a good source for using in the treatment of several diseases such as neural injuries, liver fibrosis, and Cohrn's disease. Here, we provided an overview of TDSCs particular stem cells from human exfoliated deciduous teeth and clinical application of them. Moreover, we highlighted molecular mechanisms involved in the regulation of dental stem cells fate.
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Affiliation(s)
- Ghazaleh Baniebrahimi
- Department of Pediatric Dentistry, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
| | - Razieh Khanmohammadi
- Department of Pediatric Dentistry, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Mir
- Department of Pediatric Dentistry, School of Dentistry, Zahedan University of Medical Sciences, Zahedan, Iran
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Koutsoumparis A, Vassili A, Bakopoulou A, Ziouta A, Tsiftsoglou AS. Erythropoietin (rhEPOa) promotes endothelial transdifferentiation of stem cells of the apical papilla (SCAP). Arch Oral Biol 2018; 96:96-103. [PMID: 30205239 DOI: 10.1016/j.archoralbio.2018.09.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 08/10/2018] [Accepted: 09/01/2018] [Indexed: 01/09/2023]
Abstract
OBJECTIVE Mesenchymal stem cells (MSCs) have attracted worldwide attention for their capacity to repair damaged tissue, immunosuppression, ability to differentiate into several cell types and their secretome. Earlier studies have demonstrated their angiogenic potential in vitro and in vivo. However, little is known regarding pro-angiogenic inducers of stable endothelial transdifferentiation of MSCs. Here, we employed human MSCs from the Apical Papilla (SCAP) and investigated whether recombinant human erythropoietin-alpha (rhEPOa) could act as such inducer. DESIGN Cultured SCAP cells were exposed to rhEPOa and assessed for cell growth kinetics, viability and morphology, as well as their capacity to form capillary tubule structures in selected microenvironments. RT-PCR was used to monitor endothelial markers and activation of EPO/EPOR pathway signaling components; while gelatin zymographies to assess activation of MMP-2. RESULTS rhEPOa treatment initially (48 h) accelerated cell proliferation and allowed SCAP to sprout micro-tubular structures. Morphological and biochemical differentiation was accompanied by activation of MMP-2 and upregulation of PECAM-1, VEGFR2, vWF and VE-cadherin/CDH5. SCAP expressed the cognate EPO-R, while rhEPOa-treated SCAP exhibited higher expression of molecules involved in EPO/EPOR pathway (EPOR and JAK2). CONCLUSION rhEPOa is capable of promoting endothelial transdifferentiation of SCAP which may be of clinical value in treating of ischemic disorders.
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Affiliation(s)
- Anastasios Koutsoumparis
- Laboratory of Pharmacology, School of Pharmaceutical Sciences, Faculty of Health Sciences, Aristotle University of Thessaloniki (A.U.Th), Thessaloniki, GR-54124, Greece
| | - Angelina Vassili
- Laboratory of Pharmacology, School of Pharmaceutical Sciences, Faculty of Health Sciences, Aristotle University of Thessaloniki (A.U.Th), Thessaloniki, GR-54124, Greece
| | - Athina Bakopoulou
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki (A.U.Th), Thessaloniki, GR-54124, Greece
| | - Argyro Ziouta
- Laboratory of Pharmacology, School of Pharmaceutical Sciences, Faculty of Health Sciences, Aristotle University of Thessaloniki (A.U.Th), Thessaloniki, GR-54124, Greece
| | - Asterios S Tsiftsoglou
- Laboratory of Pharmacology, School of Pharmaceutical Sciences, Faculty of Health Sciences, Aristotle University of Thessaloniki (A.U.Th), Thessaloniki, GR-54124, Greece.
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Whiting D, Chung WO, Johnson JD, Paranjpe A. Characterization of the Cellular Responses of Dental Mesenchymal Stem Cells to the Immune System. J Endod 2018; 44:1126-1131. [PMID: 29884336 DOI: 10.1016/j.joen.2018.03.018] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 03/26/2018] [Accepted: 03/31/2018] [Indexed: 01/09/2023]
Abstract
INTRODUCTION Dental stem cells have gained importance recently and are being used for various purposes in regenerative medicine and dentistry. Although much research has been done to show the various properties of these dental stem cells, the immunomodulatory properties of some of these stem cells are still unknown. This is important considering these cells are being used routinely. Therefore, the aim of this study was to investigate the interactions between the activated immune cells and 3 types of dental-derived mesenchymal stem cells: dental pulp stem cells, stem cells from human exfoliated deciduous teeth, and stem cells of the apical papilla (SCAP). METHODS SCAP, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, and periodontal ligament fibroblasts were cultured, and various assays were performed including a proliferation assay, flow cytometric analysis, lactate dehydrogenase and chromium-51 cytotoxicity assays, and an enzyme-linked immunosorbent assay to evaluate the interactions of these dental stem cells when cocultured with either peripheral blood mononuclear cells or natural killer cells. RESULTS SCAP were less resistant to immune cell-mediated cytotoxicity as seen from the results obtained from the LDH and chromium-51 cytotoxicity assays. The flow cytometric analysis showed a lower resilience of SCAP to cytotoxic compounds. The enzyme-linked immunosorbent assay results demonstrated that the SCAP induced high levels of proinflammatory cytokine secretion compared with the other dental stem cells. CONCLUSIONS SCAP did not perform as well as the other dental stem cells. This could in turn affect their survival and differentiation abilities as well as their functionality. This may be an important aspect to consider when selecting dental stem cells for various regenerative procedures.
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Affiliation(s)
- Dean Whiting
- Department of Endodontics, University of Washington, Seattle, Washington
| | - Whasun Oh Chung
- Department of Oral Health Sciences, University of Washington, Seattle, Washington
| | - James D Johnson
- Department of Endodontics, University of Washington, Seattle, Washington
| | - Avina Paranjpe
- Department of Endodontics, University of Washington, Seattle, Washington.
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Abstract
Creating an optimal microenvironment that supports angiogenesis, cell-cell cross talk, cell migration, and differentiation is crucial for pulp/dentin regeneration. It was shown that dental stem cells being seeded onto a scaffold and transplanted in vivo could give rise to a new tissue similar to that of the native pulp. However, the unique structure of the tooth with a pulp space encased within hard dentin allows only a single blood supply from a small apical opening located at the apex of the root canals. Therefore, a further strategy that can address this limitation such as the incorporation of endothelial/endothelial progenitor cells or cells with high angiogenic potential into the transplant is required so that the added cells can contribute to the vascularization within the implant. However, the placement of 2 or more different cell types inside 3-dimensional porous scaffolds is technologically challenging. In contrast to the conventional scaffolding approach, self-assembly of monodispersed cells into 3-dimensional tissue mimics permits true physiological interactions between and among different types of cells without any influence from a secondary material. In this review, we discuss potential strategies that can be used in vasculature engineering in dental pulp regeneration with a specific emphasis on combining prevascularization and scaffold-based or scaffold-free approaches.
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Affiliation(s)
| | - Chengfei Zhang
- Endodontology, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China.
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Ebrahimi Dastgurdi M, Ejeian F, Nematollahi M, Motaghi A, Nasr-Esfahani MH. Comparison of two digestion strategies on characteristics and differentiation potential of human dental pulp stem cells. Arch Oral Biol 2018; 93:74-79. [PMID: 29852380 DOI: 10.1016/j.archoralbio.2018.05.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2017] [Revised: 05/09/2018] [Accepted: 05/10/2018] [Indexed: 01/09/2023]
Abstract
OBJECTIVE This study aimed to compare the behavior of dental pulp stem cells (DPSCs) after isolation using solutions containing either collagenase/dispase or collagenase alone. DESIGN DPSCs were isolated by two digestion methods (collagenase/dispase or collagenase alone) from human third molars. Immunophenotypic features were confirmed by flow cytometry for cell markers STRO-1, cluster of differentiation (CD) 146, CD45, and collagen type-I. The proliferation potential of cells was evaluated by 5-bromo-2'-deoxyuridine (brdU) incorporation assay, and finally they were assessed for multi-lineage differentiation potential. Data were analyzed using one-way analysis of variance and independent t-tests. RESULTS DPSCs isolated by either method showed similar levels of STRO-1, CD45, and collagen type-I and similar incorporation of brdU (P > 0.05). However, DPSCs obtained by collagenase I/dispase treatment had significantly higher numbers of CD146+ cells and osteogenic and chondrogenic capacities compared to those obtained by treatment with collagenase I alone (P < 0.05). On the other hand, more STRO-1+/CD164-DPSCs were found in the collagenase alone group with higher adipogenic potential. CONCLUSIONS Different enzyme solutions gave rise to different populations of DPSCs. Dispase enhanced isolation of CD146+ DPSCs probably by disrupting the basement membranes of blood vessels and releasing DPCSs embedded in the perivascular niche. Furthermore, the differentiation potential of DPSCs was influenced by the change in enzyme solution.
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Affiliation(s)
| | - Fatemeh Ejeian
- Department of Cell and Molecular Biology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Marzie Nematollahi
- Department of Cell and Molecular Biology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Ahmad Motaghi
- Department of Oral and Maxillofacial Surgery, Isfahan (Khorasgan) Branch, I.A.U., Isfahan, Iran
| | - Mohammad Hossein Nasr-Esfahani
- Department of Cell and Molecular Biology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
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