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Qiao L, Zheng X, Xie C, Wang Y, Ye L, Zhao J, Liu J. Bioactive Materials in Vital Pulp Therapy: Promoting Dental Pulp Repair Through Inflammation Modulation. Biomolecules 2025; 15:258. [PMID: 40001561 PMCID: PMC11853510 DOI: 10.3390/biom15020258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/11/2025] [Accepted: 01/21/2025] [Indexed: 02/27/2025] Open
Abstract
With the paradigm shift towards minimally invasive biologic therapies, vital pulp therapy (VPT) has been receiving increasing attention. Currently, bioactive materials (BMs), including MTAs, Biodentine, Bioaggregate, and iRoot BP Plus, are clinically widely used for the repair of damaged pulp tissue. Emerging evidence highlights the crucial role of inflammation in pulp repair, with mild to moderate inflammation serving as a prerequisite for promoting pulp repair. BMs play a pivotal role in regulating the balance between inflammatory response and reparative events for dentine repair. Despite their widespread application as pulp-capping agents, the precise mechanisms underlying the actions of BMs remain poorly understood. A comprehensive literature review was conducted, covering studies on the inflammatory responses induced by BMs published up to December 2023. Sources were identified through searches of PubMed and MEDLINE databases, supplemented by manual review of cross-references from relevant studies. The purpose of this article is to discuss diverse mechanisms by which BMs may regulate the balance between tissue inflammation and repair. A deeper understanding of these regulatory mechanisms will facilitate the optimization of current pulp-capping agents, enabling the development of targeted regenerative strategies to achieve superior clinical outcomes.
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Affiliation(s)
- Liang Qiao
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (L.Q.); (X.Z.); (C.X.); (Y.W.); (L.Y.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Xueqing Zheng
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (L.Q.); (X.Z.); (C.X.); (Y.W.); (L.Y.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Chun Xie
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (L.Q.); (X.Z.); (C.X.); (Y.W.); (L.Y.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Yaxin Wang
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (L.Q.); (X.Z.); (C.X.); (Y.W.); (L.Y.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Lu Ye
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (L.Q.); (X.Z.); (C.X.); (Y.W.); (L.Y.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Jiajia Zhao
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (L.Q.); (X.Z.); (C.X.); (Y.W.); (L.Y.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Jiarong Liu
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (L.Q.); (X.Z.); (C.X.); (Y.W.); (L.Y.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
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Eivazi Zadeh Z, Nour S, Kianersi S, Jonidi Shariatzadeh F, Williams RJ, Nisbet DR, Bruggeman KF. Mining human clinical waste as a rich source of stem cells for neural regeneration. iScience 2024; 27:110307. [PMID: 39156636 PMCID: PMC11326931 DOI: 10.1016/j.isci.2024.110307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/20/2024] Open
Abstract
Neural diseases are challenging to treat and are regarded as one of the major causes of disability and morbidity in the world. Stem cells can provide a solution, by offering a mechanism to replace damaged circuitry. However, obtaining sufficient cell sources for neural regeneration remains a significant challenge. In recent years, waste-derived stem(-like) cells (WDS-lCs) extracted from both prenatal and adult clinical waste tissues/products, have gained increasing attention for application in neural tissue repair and remodeling. This often-overlooked pool of cells possesses favorable characteristics; including self-renewal, neural differentiation, secretion of neurogenic factors, cost-effectiveness, and low ethical concerns. Here, we offer a perspective regarding the biological properties, extraction protocols, and preclinical and clinical treatments where prenatal and adult WDS-lCs have been utilized for cell replacement therapy in neural applications, and the challenges involved in optimizing these approaches toward patient led therapies.
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Affiliation(s)
- Zahra Eivazi Zadeh
- Department of Biomedical Engineering, University of Melbourne, Parkville, VIC 3010, Australia
- The Graeme Clark Institute, University of Melbourne, Melbourne, VIC, Australia
| | - Shirin Nour
- Department of Biomedical Engineering, University of Melbourne, Parkville, VIC 3010, Australia
- The Graeme Clark Institute, University of Melbourne, Melbourne, VIC, Australia
- Polymer Science Group, Department of Chemical Engineering, University of Melbourne, Parkville, VIC 3010, Australia
| | - Sogol Kianersi
- Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences, University of Galway, Galway, Ireland
| | | | - Richard J. Williams
- The Graeme Clark Institute, University of Melbourne, Melbourne, VIC, Australia
- iMPACT, School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
| | - David R. Nisbet
- Department of Biomedical Engineering, University of Melbourne, Parkville, VIC 3010, Australia
- The Graeme Clark Institute, University of Melbourne, Melbourne, VIC, Australia
- ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, ANU College of Health & Medicine, Canberra, ACT, Australia
- Research School of Chemistry, ANU College of Science, Canberra, ACT, Australia
- Melbourne Medical School, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Melbourne, VIC, Australia
- Founder and Scientific Advisory of Nano Status, Building 137, Sullivans Creek Rd, ANU, Acton, Canberra, ACT, Australia
| | - Kiara F. Bruggeman
- Laboratory of Advanced Biomaterials Research, School of Engineering, Australian National University, Canberra, ACT, Australia
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Hardin LT, Abid N, Vang D, Han X, Thor D, Ojcius DM, Xiao N. miRNAs mediate the impact of smoking on dental pulp stem cells via the p53 pathway. Toxicol Sci 2024; 200:47-56. [PMID: 38636493 DOI: 10.1093/toxsci/kfae042] [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] [Indexed: 04/20/2024] Open
Abstract
Cigarette smoke changes the genomic and epigenomic imprint of cells. In this study, we investigated the biological consequences of extended cigarette smoke exposure on dental pulp stem cells (DPSCs) and the potential roles of miRNAs. DPSCs were treated with various doses of cigarette smoke condensate (CSC) for up to 6 weeks. Cell proliferation, survival, migration, and differentiation were evaluated. Cytokine and miRNA expression were profiled. The results showed that extended exposure to CSC significantly impaired the regenerative capacity of the DPSCs. Bioinformatic analysis showed that the cell cycle pathway, cancer pathways (small cell lung cancer, pancreatic, colorectal, and prostate cancer), and pathways for TNF, TGF-β, p53, PI3K-Akt, mTOR, and ErbB signal transduction, were associated with altered miRNA profiles. In particular, 3 miRNAs has-miR-26a-5p, has-miR-26b-5p, and has-miR-29b-3p fine-tune the p53 and cell cycle signaling pathways to regulate DPSC cellular activities. The work indicated that miRNAs are promising targets to modulate stem cell regeneration and understanding miRNA-targeted genes and their associated pathways in smoking individuals have significant implications for disease control and prevention.
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Affiliation(s)
- Leyla Tahrani Hardin
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, California 94103, USA
| | - Nabil Abid
- Department of Molecular and Cellular Biology, High Institute of Biotechnology of Monastir, University of Monastir, Monastir, 5000, Tunisia
- Laboratory of Transmissible Diseases and Biological Active Substances LR99ES27, Faculty of Pharmacy of Monastir, University of Monastir, Monastir, 5000, Tunisia
| | - David Vang
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, California 94103, USA
| | - Xiaoyuan Han
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, California 94103, USA
| | - Der Thor
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, California 94103, USA
| | - David M Ojcius
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, California 94103, USA
| | - Nan Xiao
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, California 94103, USA
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Wei X, Xu H, Zhou M, Zhou Q, Li M, Liu Y. Chemically modified microRNA delivery via DNA tetrahedral frameworks for dental pulp regeneration. J Nanobiotechnology 2024; 22:150. [PMID: 38575923 PMCID: PMC11318316 DOI: 10.1186/s12951-024-02393-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 03/10/2024] [Indexed: 04/06/2024] Open
Abstract
Dental pulp regeneration is a promising strategy for addressing tooth disorders. Incorporating this strategy involves the fundamental challenge of establishing functional vascular networks using dental pulp stem cells (DPSCs) to support tissue regeneration. Current therapeutic approaches lack efficient and stable methods for activating DPSCs. In the study, we used a chemically modified microRNA (miRNA)-loaded tetrahedral-framework nucleic acid nanostructure to promote DPSC-mediated angiogenesis and dental pulp regeneration. Incorporating chemically modified miR-126-3p into tetrahedral DNA nanostructures (miR@TDNs) represents a notable advancement in the stability and efficacy of miRNA delivery into DPSCs. These nanostructures enhanced DPSC proliferation, migration, and upregulated angiogenesis-related genes, enhancing their paracrine signaling effects on endothelial cells. This enhanced effect was substantiated by improvements in endothelial cell tube formation, migration, and gene expression. Moreover, in vivo investigations employing matrigel plug assays and ectopic dental pulp transplantation confirmed the potential of miR@TDNs in promoting angiogenesis and facilitating dental pulp regeneration. Our findings demonstrated the potential of chemically modified miRNA-loaded nucleic acid nanostructures in enhancing DPSC-mediated angiogenesis and supporting dental pulp regeneration. These results highlighted the promising role of chemically modified nucleic acid-based delivery systems as therapeutic agents in regenerative dentistry and tissue engineering.
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Affiliation(s)
- Xiaoling Wei
- Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, 200001, China
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China
| | - Huaxing Xu
- Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, 200001, China
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China
| | - Mengqi Zhou
- Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, 200001, China
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China
| | - Qiangqiang Zhou
- Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, 200001, China
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China
| | - Mingqiang Li
- School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
| | - Yuehua Liu
- Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, 200001, China.
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China.
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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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Yu H, Habibi M, Motamedi K, Semirumi DT, Ghorbani A. Utilizing stem cells in reconstructive treatments for sports injuries: An innovative approach. Tissue Cell 2023; 83:102152. [PMID: 37451009 DOI: 10.1016/j.tice.2023.102152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 06/17/2023] [Accepted: 06/29/2023] [Indexed: 07/18/2023]
Abstract
Orthopedic tissue engineering is a rapidly evolving field that holds great promise for the reconstruction and natural repair of bone and joint tissues. Bone loss, fractures, and joint degeneration are common problems that can result from a variety of pathological conditions, and their restoration and replacement are essential not only for functional purposes but also for improving the quality of life for patients. However, current methods rely heavily on artificial materials that can potentially lead to further tissue damage, making tissue engineering a highly attractive alternative. This innovative approach involves the utilization of stem cells (SCs), which are seeded onto a scaffold to form a biological complex. Among these SCs, mesenchymal stem cells (MSCs) extracted from bone marrow and adipose tissue have shown immense potential for bone and joint tissue regeneration. The success of orthopedic tissue engineering is contingent on the careful selection of appropriate scaffolds and inducing molecules, which play a critical role in carrying and supporting cells and inducing their differentiation. This review article comprehensively analyzes the three vital aspects of orthopedic tissue engineering - SCs, scaffolds, and inducing molecules - in order to provide a deeper understanding of this emerging field and its potential for the future of orthopedic medicine.
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Affiliation(s)
- Hongying Yu
- Physical Education Department, Jingchu University of Technology, Jingmen 448000, Hubei, China.
| | - M Habibi
- Faculty of Architecture and Urbanism, UTE University, Calle Rumipamba S/N and Bourgeois, Quito, Ecuador; Department of Biomaterials, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai 600 077, India; Institute of Research and Development, Duy Tan University, Da Nang 550000, Viet Nam
| | - K Motamedi
- Student Research Committee, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - D T Semirumi
- Department of Biomaterials, Islamic Azad University, Isfahan, Iran.
| | - A Ghorbani
- Biotechnology Department, Falavarjan Branch, Islamic Azad University, Isfahan, Iran
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Ariano A, Posa F, Storlino G, Mori G. Molecules Inducing Dental Stem Cells Differentiation and Bone Regeneration: State of the Art. Int J Mol Sci 2023; 24:9897. [PMID: 37373044 DOI: 10.3390/ijms24129897] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 05/30/2023] [Accepted: 06/05/2023] [Indexed: 06/29/2023] Open
Abstract
Teeth include mesenchymal stem cells (MSCs), which are multipotent cells that promote tooth growth and repair. Dental tissues, specifically the dental pulp and the dental bud, constitute a relevant source of multipotent stem cells, known as dental-derived stem cells (d-DSCs): dental pulp stem cells (DPSCs) and dental bud stem cells (DBSCs). Cell treatment with bone-associated factors and stimulation with small molecule compounds are, among the available methods, the ones who show excellent advantages promoting stem cell differentiation and osteogenesis. Recently, attention has been paid to studies on natural and non-natural compounds. Many fruits, vegetables, and some drugs contain molecules that can enhance MSC osteogenic differentiation and therefore bone formation. The purpose of this review is to examine research work over the past 10 years that has investigated two different types of MSCs from dental tissues that are attractive targets for bone tissue engineering: DPSCs and DBSCs. The reconstruction of bone defects, in fact, is still a challenge and therefore more research is needed; the articles reviewed are meant to identify compounds useful to stimulate d-DSC proliferation and osteogenic differentiation. We only consider the results of the research which is encouraging, assuming that the mentioned compounds are of some importance for bone regeneration.
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Affiliation(s)
- Anastasia Ariano
- Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy
| | - Francesca Posa
- Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy
| | - Giuseppina Storlino
- Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy
| | - Giorgio Mori
- Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy
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Li P, Ou Q, Shi S, Shao C. Immunomodulatory properties of mesenchymal stem cells/dental stem cells and their therapeutic applications. Cell Mol Immunol 2023; 20:558-569. [PMID: 36973490 PMCID: PMC10040934 DOI: 10.1038/s41423-023-00998-y] [Citation(s) in RCA: 90] [Impact Index Per Article: 45.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 03/02/2023] [Indexed: 03/29/2023] Open
Abstract
Mesenchymal stem/stromal cells (MSCs) are widely distributed in the body and play essential roles in tissue regeneration and homeostasis. MSCs can be isolated from discarded tissues, expanded in vitro and used as therapeutics for autoimmune diseases and other chronic disorders. MSCs promote tissue regeneration and homeostasis by primarily acting on immune cells. At least six different types of MSCs have been isolated from postnatal dental tissues and have remarkable immunomodulatory properties. Dental stem cells (DSCs) have been demonstrated to have therapeutic effects on several systemic inflammatory diseases. Conversely, MSCs derived from nondental tissues such as the umbilical cord exhibit great benefits in the management of periodontitis in preclinical studies. Here, we discuss the main therapeutic uses of MSCs/DSCs, their mechanisms, extrinsic inflammatory cues and the intrinsic metabolic circuitries that govern the immunomodulatory functions of MSCs/DSCs. Increased understanding of the mechanisms underpinning the immunomodulatory functions of MSCs/DSCs is expected to aid in the development of more potent and precise MSC/DSC-based therapeutics.
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Affiliation(s)
- Peishan Li
- The First Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University, Suzhou, PR China
| | - Qianmin Ou
- South China Center of Craniofacial Stem Cell Research, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, PR China
| | - Songtao Shi
- South China Center of Craniofacial Stem Cell Research, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, PR China.
| | - Changshun Shao
- The First Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University, Suzhou, PR China.
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Abdalla MM, Lung CYK, Bijle MN, Yiu CKY. Physicochemical Properties and Inductive Effect of Calcium Strontium Silicate on the Differentiation of Human Dental Pulp Stem Cells for Vital Pulp Therapies: An In Vitro Study. MATERIALS (BASEL, SWITZERLAND) 2022; 15:5854. [PMID: 36079235 PMCID: PMC9457449 DOI: 10.3390/ma15175854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/05/2022] [Accepted: 08/22/2022] [Indexed: 06/15/2023]
Abstract
The development of biomaterials that exhibit profound bioactivity and stimulate stem cell differentiation is imperative for the success and prognosis of vital pulp therapies. The objectives were to (1) synthesize calcium strontium silicate (CSR) ceramic through the sol−gel process (2) investigate its physicochemical properties, bioactivity, cytocompatibility, and its stimulatory effect on the differentiation of human dental pulp stem cells (HDPSC). Calcium silicate (CS) and calcium strontium silicate (CSR) were synthesized by the sol−gel method and characterized by x-ray diffraction (XRD). Setting time, compressive strength, and pH were measured. The in vitro apatite formation was evaluated by SEM-EDX and FTIR. The NIH/3T3 cell viability was assessed using an MTT assay. The differentiation of HDPSC was evaluated using alkaline phosphatase activity (ALP), and Alizarin red staining (ARS). Ion release of Ca, Sr, and Si was measured using inductive coupled plasma optical emission spectroscopy (ICP-OES). XRD showed the synthesis of (CaSrSiO4). The initial and final setting times were significantly shorter in CSR (5 ± 0.75 min, 29 ± 1.9 min) than in CS (8 ± 0.77 min, 31 ± 1.39 min), respectively (p < 0.05). No significant difference in compressive strength was found between CS and CSR (p > 0.05). CSR demonstrated higher apatite formation and cell viability than CS. The ALP activity was significantly higher in CSR 1.16 ± 0.12 than CS 0.92 ± 0.15 after 14 d of culture (p < 0.05). ARS showed higher mineralization in CSR than CS after 14 and 21 d culture times. CSR revealed enhanced differentiation of HDPSC, physicochemical properties, and bioactivity compared to CS.
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Affiliation(s)
- Mohamed Mahmoud Abdalla
- Paediatric Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China
- Dental Biomaterials, Faculty of Dental Medicine, Al-Azhar University, Cairo 11651, Egypt
| | - Christie Y. K. Lung
- Dental Materials Science, Applied Oral Sciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China
| | - Mohammed Nadeem Bijle
- Paediatric Dentistry, Department of Clinical Sciences, College of Dentistry, Ajman University, Ajman P.O. Box 346, United Arab Emirates
| | - Cynthia Kar Yung Yiu
- Paediatric Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China
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Different Sources of Mesenchymal Stem Cells for Tissue Regeneration: A Guide to Identifying the Most Favorable One in Orthopedics and Dentistry Applications. Int J Mol Sci 2022; 23:ijms23116356. [PMID: 35683035 PMCID: PMC9181542 DOI: 10.3390/ijms23116356] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 05/31/2022] [Accepted: 06/03/2022] [Indexed: 12/04/2022] Open
Abstract
The success of regenerative medicine in various clinical applications depends on the appropriate selection of the source of mesenchymal stem cells (MSCs). Indeed, the source conditions, the quality and quantity of MSCs, have an influence on the growth factors, cytokines, extracellular vesicles, and secrete bioactive factors of the regenerative milieu, thus influencing the clinical result. Thus, optimal source selection should harmonize this complex setting and ensure a well-personalized and effective treatment. Mesenchymal stem cells (MSCs) can be obtained from several sources, including bone marrow and adipose tissue, already used in orthopedic regenerative applications. In this sense, for bone, dental, and oral injuries, MSCs could provide an innovative and effective therapy. The present review aims to compare the properties (proliferation, migration, clonogenicity, angiogenic capacity, differentiation potential, and secretome) of MSCs derived from bone marrow, adipose tissue, and dental tissue to enable clinicians to select the best source of MSCs for their clinical application in bone and oral tissue regeneration to delineate new translational perspectives. A review of the literature was conducted using the search engines Web of Science, Pubmed, Scopus, and Google Scholar. An analysis of different publications showed that all sources compared (bone marrow mesenchymal stem cells (BM-MSCs), adipose tissue mesenchymal stem cells (AT-MSCs), and dental tissue mesenchymal stem cells (DT-MSCs)) are good options to promote proper migration and angiogenesis, and they turn out to be useful for gingival, dental pulp, bone, and periodontal regeneration. In particular, DT-MSCs have better proliferation rates and AT and G-MSC sources showed higher clonogenicity. MSCs from bone marrow, widely used in orthopedic regenerative medicine, are preferable for their differentiation ability. Considering all the properties among sources, BM-MSCs, AT-MSCs, and DT-MSCs present as potential candidates for oral and dental regeneration.
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Kulakowski D, Phansalkar RM, Leme-Kraus AA, McAlpine J, Chen SN, Pauli GF, Ravindran S, Bedran-Russo AK. Galloylated proanthocyanidins in dentin matrix exhibit biocompatibility and induce differentiation in dental stem cells. J BIOACT COMPAT POL 2022; 37:220-230. [PMID: 37465414 PMCID: PMC10353770 DOI: 10.1177/08839115221095154] [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: 07/20/2023]
Abstract
Aim Grape seed extract contains a complex mixture of proanthocyanidins (PACs), a plant biopolymer used as a biomaterial to improve reparative and preventive dental therapies. Co-polymerization of PACs with type I collagen mechanically reinforces the dentin extracellular matrix. This study assessed the biocompatibility of PACs from grape seed extract on dental pulp stem cells (DPSCs) in a model simulating leaching through dentin to the pulp cavity. The aim was to determine the type of PACs (galloylated vs. non-galloylated) within grape seed extract that are most compatible with dental pulp tissue. Methodology Human demineralized dentin was treated with selectively-enriched dimeric PACs prepared from grape seed extract using liquid-liquid chromatography. DPSCs were cultured within a 2D matrix and exposed to PAC-treated dentin extracellular matrix. Cell proliferation was measured using the MTS assay and expression of odontoblastic genes was analyzed by qRT-PCR. Categorization of PACs leaching from dentin was performed using HPLC-MS. Results Enriched dimeric fractions containing galloylated PACs increased the expression of certain odontoblastic genes in DPSCs, including Runt-related transcription factor 2 (RUNX2), vascular endothelial growth factor (VEGF), bone morphogenetic protein 2 (BMP2), basic fibroblast growth factor (FGF2), dentin sialophosphoprotein (DSPP) and collagen, type I, alpha 1 (COLI). Galloylated dimeric PACs also exhibited minor effects on DPSC proliferation, resulting in a decrease compared to control after five days of treatment. The non-galloylated dimer fraction had no effect on these genes or on DPSC proliferation. Conclusions Galloylated PACs are biocompatible with DPSCs and may exert a beneficial effect on cells within dental pulp tissue. The observed increase in odontoblastic genes induced by galloylated PACs together with a decrease in DPSC proliferation is suggestive of a shift toward cell differentiation. This data supports the use of dimeric PACs as a safe biomaterial, with galloylated dimeric PACs exhibiting potential benefits to odontoblasts supporting dentin regeneration.
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Affiliation(s)
- Daniel Kulakowski
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States
| | - Rasika M. Phansalkar
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States
| | - Ariene A Leme-Kraus
- Department of Restorative Dentistry, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois 60612, United States
| | - James McAlpine
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States
| | - Shao-Nong Chen
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States
| | - Guido F. Pauli
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States
| | - Sriram Ravindran
- Department of Oral Biology, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois 60612, United States
| | - Ana K. Bedran-Russo
- Department of Restorative Dentistry, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois 60612, United States
- Department of General Dental Sciences, School of Dentistry, Marquette University, Milwaukee, Wisconsin 53233, United States
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12
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da Rocha EA, Alvarez MMP, Pelosine AM, Carrilho MRO, Tersariol ILS, Nascimento FD. Laser Photobiomodulation 808 nm: Effects on Gene Expression in Inflammatory and Osteogenic Biomarkers in Human Dental Pulp Stem Cells. Front Pharmacol 2022; 12:782095. [PMID: 35111053 PMCID: PMC8802107 DOI: 10.3389/fphar.2021.782095] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 10/19/2021] [Indexed: 12/20/2022] Open
Abstract
The tissue engineering of dental oral tissue is tackling significant advances and the use of stem cells promises to boost the therapeutical approaches of regenerative dentistry. Despite advances in this field, the literature is still scarce regarding the modulatory effect of laser photobiomodulation (PBM) on genes related to inflammation and osteogenesis in Postnatal Human Dental Pulp Stem cells (DPSCs). This study pointedly investigated the effect of PBM treatment in proliferation, growth and differentiation factors, mineralization, and extracellular matrix remodeling genes in DPSCs. Freshly extracted human third molars were used as a source for DPSCs isolation. The isolated DPSCs were stimulated to an inflammatory state, using a lipopolysaccharide (LPS) model, and then subjected or not to laser PBM. Each experiment was statistically evaluated according to the sample distribution. A total of 85 genes related to inflammation and osteogenesis were evaluated regarding their expression by RT-PCR. Laser PBM therapy has shown to modulate several genes expression in DPSCs. PBM suppressed the expression of inflammatory gene TNF and RANKL and downregulated the gene expression for VDR and proteolytic enzymes cathepsin K, MMP-8 and MMP-9. Modulation of gene expression for proteinase-activated receptors (PARs) following PBM varied among different PARs. As expected, PBM blocked the odontoblastic differentiation of DPSCs when subjected to LPS model. Conversely, PBM has preserved the odontogenic potential of DPSCs by increasing the expression of TWIST-1/RUNEX-2/ALP signaling axis. PBM therapy notably played a role in the DPSCs genes expression that mediate inflammation process and tissue mineralization. The present data opens a new perspective for PBM therapy in mineralized dental tissue physiology.
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Affiliation(s)
- Elaine A da Rocha
- Technology Research Center, Mogi das Cruzes University, Mogi das Cruzes, Brazil
| | - Marcela M P Alvarez
- Department of Biochemistry, Federal University of São Paulo, São Paulo, Brazil
| | - Agatha M Pelosine
- Interdisciplinary Center of Biochemical Investigation, University of Mogi das Cruzes, Mogi das Cruzes, Brazil
| | | | | | - Fábio D Nascimento
- Technology Research Center, Mogi das Cruzes University, Mogi das Cruzes, Brazil.,Department of Biochemistry, Federal University of São Paulo, São Paulo, Brazil.,Interdisciplinary Center of Biochemical Investigation, University of Mogi das Cruzes, Mogi das Cruzes, Brazil
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13
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Dental Pulp Stem Cell Heterogeneity: Finding Superior Quality "Needles" in a Dental Pulpal "Haystack" for Regenerative Medicine-Based Applications. Stem Cells Int 2022; 2022:9127074. [PMID: 35027930 PMCID: PMC8752304 DOI: 10.1155/2022/9127074] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 11/03/2021] [Indexed: 12/14/2022] Open
Abstract
Human dental pulp stem/stromal cells (hDPSCs) derived from the permanent secondary dentition are recognised to possess certain advantageous traits, which support their potential use as a viable source of mesenchymal stem/stromal cells (MSCs) for regenerative medicine-based applications. However, the well-established heterogeneous nature of hDPSC subpopulations, coupled with their limited numbers within dental pulp tissues, has impeded our understanding of hDPSC biology and the translation of sufficient quantities of these cells from laboratory research, through successful therapy development and clinical applications. This article reviews our current understanding of hDPSC biology and the evidence underpinning the molecular basis of their heterogeneity, which may be exploited to distinguish individual subpopulations with specific or superior characteristics for regenerative medicine applications. Pertinent unanswered questions which still remain, regarding the developmental origins, hierarchical organisation, and stem cell niche locations of hDPSC subpopulations and their roles in hDPSC heterogeneity and functions, will further be explored. Ultimately, a greater understanding of how key features, such as specific cell surface, senescence and other relevant genes, and protein and metabolic markers, delineate between hDPSC subpopulations with contrasting stemness, proliferative, multipotency, immunomodulatory, anti-inflammatory, and other relevant properties is required. Such knowledge advancements will undoubtedly lead to the development of novel screening, isolation, and purification strategies, permitting the routine and effective identification, enrichment, and expansion of more desirable hDPSC subpopulations for regenerative medicine-based applications. Furthermore, such innovative measures could lead to improved cell expansion, manufacture, and banking procedures, thereby supporting the translational development of hDPSC-based therapies in the future.
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14
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The ERα/KDM6B regulatory axis modulates osteogenic differentiation in human mesenchymal stem cells. Bone Res 2022; 10:3. [PMID: 34992221 PMCID: PMC8738748 DOI: 10.1038/s41413-021-00171-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/11/2021] [Accepted: 08/02/2021] [Indexed: 01/19/2023] Open
Abstract
Osteoporosis is a highly prevalent public health burden associated with an increased risk of bone fracture, particularly in aging women. Estrogen, an important medicinal component for the preventative and therapeutic treatment of postmenopausal osteoporosis, induces osteogenesis by activating the estrogen receptor signaling pathway and upregulating the expression of osteogenic genes, such as bone morphogenetic proteins (BMPs). The epigenetic regulation of estrogen-mediated osteogenesis, however, is still unclear. In this report, we found that estrogen significantly induced the expression of lysine-specific demethylase 6B (KDM6B) and that KDM6B depletion by shRNAs led to a significant reduction in the osteogenic potential of DMSCs. Mechanistically, upon estrogen stimulation, estrogen receptor-α (ERα) was recruited to the KDM6B promoter, directly enhancing KDM6B expression. Subsequently, KDM6B was recruited to the BMP2 and HOXC6 promoters, resulting in the removal of H3K27me3 marks and activating the transcription of BMP2 and HOXC6, the master genes of osteogenic differentiation. Furthermore, we found that estrogen enhanced DMSC osteogenesis during calvarial bone regeneration and that estrogen's pro-osteogenic effect was dependent on KDM6B in vivo. Taken together, our results demonstrate the vital role of the ERα/KDM6B regulatory axis in the epigenetic regulation of the estrogen-dependent osteogenic response.
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15
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Huang L, Zheng Z, Bai D, Han X. Stem Cells from Human Exfoliated Deciduous Teeth and their Promise as Preventive and Therapeutic Strategies for Neurological Diseases and Injuries. Curr Stem Cell Res Ther 2021; 17:527-536. [PMID: 34967291 DOI: 10.2174/1574888x17666211229155533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/04/2021] [Accepted: 11/15/2021] [Indexed: 11/22/2022]
Abstract
Stem cells from human exfoliated deciduous teeth (SHEDs) are relatively easy to isolate from exfoliated deciduous teeth, which are obtained via dental therapy as biological waste. SHEDs originate from the embryonic neural crest and therefore have considerable potential for neurogenic differentiation. Currently, an increasing amount of research attention is focused on the therapeutic applications of SHEDs in neurological diseases and injuries. In this article, we summarize the biological characteristics of SHEDs and the potential role of SHEDs and their derivatives, including conditioned medium from SHEDs and the exosomes they secrete, in the prevention and treatment of neurological diseases and injuries.
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Affiliation(s)
- Lingyi Huang
- West China College of Stomatology/ State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
| | - Zizhuo Zheng
- West China College of Stomatology/ State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
| | - Ding Bai
- West China College of Stomatology/ State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
| | - Xianglong Han
- West China College of Stomatology/ State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
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16
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Relevance of Cellular Redox Homeostasis for Vital Functions of Human Dental Pulp Cells. Antioxidants (Basel) 2021; 11:antiox11010023. [PMID: 35052527 PMCID: PMC8772760 DOI: 10.3390/antiox11010023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 12/17/2021] [Accepted: 12/21/2021] [Indexed: 01/22/2023] Open
Abstract
Odontogenic MSCs are vulnerable to LPS-triggered bacterial infections, and they respond by secreting inflammatory mediators, such as IL-6, and with mineralization. Since both processes might be prone to a disturbance of the redox homeostasis, the oxidative stress influence on vital functions of human dental pulp cells (HPCs) was investigated. With these aims, a model of LPS-stimulated primary HPCs was established, and anti- and pro-oxidant substances were administered up to 21 days to measure inflammation and mineralization parameters. LPS-stimulated HPCs retained mineralization potential, which was decreased with the antioxidants NAC and fisetin and the pro-oxidant BSO. The expression of surface markers related to odontogenic commitment was influenced accordingly but counteracted by the enhanced expression of BMP2 and ALP at the transcriptional level. LPS triggers an early IL-6 production in non-odontogenic conditions, while it can be measured only after 15 days in the presence of the differentiation medium. The present study shows that HPCs functions causally depend on a tightly regulated cellular redox balance. Our data demonstrate a redox control of pulp MSC odontogenic commitment along with a potential association between an IL-6 late secretion and mineralization. These findings lay the groundwork for investigations on the molecular role of IL-6 in dental hard tissue metabolism.
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17
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Application of Selected Biomaterials and Stem Cells in the Regeneration of Hard Dental Tissue in Paediatric Dentistry-Based on the Current Literature. NANOMATERIALS 2021; 11:nano11123374. [PMID: 34947723 PMCID: PMC8709498 DOI: 10.3390/nano11123374] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 12/08/2021] [Accepted: 12/09/2021] [Indexed: 11/28/2022]
Abstract
Currently, the development of the use of biomaterials and their application in medicine is causing rapid changes in the fields of regenerative dentistry. Each year, new research studies allow for the discovery of additional possibilities of dental tissue restoration. The structure and functions of teeth are complex. They consist of several diverse tissues that need to act together to ensure the tooth’s function and durability. The integrity of a tooth’s enamel, dentin, cementum, and pulp tissue allows for successful mastication. Biomaterials that are needed in dentistry must withstand excessive loading forces, be biocompatible with the hosts’ tissues, and stable in the oral cavity environment. Moreover, each tooth’s tissue, as well as aesthetic qualities in most cases, should closely resemble the natural dental tissues. This is why tissue regeneration in dentistry is such a challenge. This scientific research focuses on paediatric dentistry, its classification of caries, and the use of biomaterials in rebuilding hard dental tissues. There are several methods described in the study, including classical conservative methods such as caries infiltration or stainless-steel crowns. Several clinical cases are present, allowing a reader to better understand the described methods. Although the biomaterials mentioned in this work are artificial, there is currently ongoing research regarding clinical stem cell applications, which have a high potential for becoming one of the most common techniques of lost dental-tissue regeneration in the near future. The current state of stem cell development is mentioned, as well as the various methods of its possible application in dentistry.
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18
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Age of the donor affects the nature of in vitro cultured human dental pulp stem cells. Saudi Dent J 2021; 33:524-532. [PMID: 34803296 PMCID: PMC8589584 DOI: 10.1016/j.sdentj.2020.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 08/26/2020] [Accepted: 09/13/2020] [Indexed: 12/13/2022] Open
Abstract
Objectives The dental pulp stem cells (DPSCs) of six donors (three young donors aged < 19 years and three adult donors aged > 25 and < 30 years) were characterized for their stem cell marker expression and differentiation potential to study the effect of donor age on DPSCs in vitro. Methods DPSCs were cultured in αMEM supplemented with 20% fetal calf serum (conventional conditions) or on fibronectin-coated flasks with neurobasal medium supplemented with B27, bFGF and EGF (alternative conditions). DPSCs were characterized by immunofluorescence staining to detect the neural crest/mesenchymal stem cells markers P75 and CD146, respectively. The differentiation potential was tested by the induction of DPSCs into osteogenic, adipogenic and glial lineages and then by detecting the corresponding markers osteocalcin, lipidtox and S100ß, respectively. Results The DPSCs of the young donors expressed CD146 only under the conventional conditions and expressed P75 regardless of the culture conditions. However, the DPSCs of adult donors expressed CD146 only under the alternative conditions and expressed P75 only under conventional conditions. Only the DPSCs of the young donors differentiated into the glial linage. The DPSCs of the adult donors differentiated more efficiently into the adipogenic linage. Osteogenic differentiation was comparable. Conclusion Donor age affects the expression of stem cell markers and differentiation potential of DPSCs. Moreover, the effect of culture conditions on DPSCs is age dependent.
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19
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Ahmed MN, Shi D, Dailey MT, Rothermund K, Drewry MD, Calabrese TC, Cui XT, Syed-Picard FN. Dental Pulp Cell Sheets Enhance Facial Nerve Regeneration via Local Neurotrophic Factor Delivery. Tissue Eng Part A 2021; 27:1128-1139. [PMID: 33164704 PMCID: PMC8616747 DOI: 10.1089/ten.tea.2020.0265] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
An effective strategy for sustained neurotrophic factor (NTF) delivery to sites of peripheral nerve injury (PNI) would accelerate healing and enhance functional recovery, addressing the major clinical challenges associated with the current standard of care. In this study, scaffold-free cell sheets were generated using human dental pulp stem/progenitor cells, that endogenously express high levels of NTFs, for use as bioactive NTF delivery systems. Additionally, the effect of fibroblast growth factor 2 (FGF2) on NTF expression by dental pulp cell (DPC) sheets was evaluated. In vitro analysis confirmed that DPC sheets express high levels of NTF messenger RNA (mRNA) and proteins, and the addition of FGF2 to DPC sheet culture increased total NTF production by significantly increasing the cellularity of sheets. Furthermore, the DPC sheet secretome stimulated neurite formation and extension in cultured neuronal cells, and these functional effects were further enhanced when DPC sheets were cultured with FGF2. These neuritogenic results were reversed by NTF inhibition substantiating that DPC sheets have a positive effect on neuronal cell activity through the production of NTFs. Further evaluation of DPC sheets in a rat facial nerve crush injury model in vivo established that in comparison with untreated controls, nerves treated with DPC sheets had greater axon regeneration through the injury site and superior functional recovery as quantitatively assessed by compound muscle action potential measurements. This study demonstrates the use of DPC sheets as vehicles for NTF delivery that could augment the current methods for treating PNIs to accelerate regeneration and enhance the functional outcome. Impact statement The major challenges associated with current treatments of peripheral nerve injuries (PNIs) are prolonged repair times and insufficient functional recovery. Dental pulp stem/progenitor cells (DPCs) are known to endogenously express high levels of neurotrophic factors (NTFs), growth factors that enhance axon regeneration. In this study, we demonstrate that scaffold-free DPC sheets can act as effective carrier systems to facilitate the delivery and retention of NTF-producing DPCs to sites of PNIs and improve functional nerve regeneration. DPC sheets have high translational feasibility and could augment the current standard of care to enhance the quality of life for patients dealing with PNIs.
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Affiliation(s)
- Meer N. Ahmed
- Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Delin Shi
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Matthew T. Dailey
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Kristi Rothermund
- Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Michelle D. Drewry
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Tia C. Calabrese
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Xinyan T. Cui
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Fatima N. Syed-Picard
- Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania USA
- Address correspondence to: Fatima N. Syed-Picard, MSE, PhD, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, 413 Salk Pavilion, 355 Sutherland Drive, Pittsburgh, PA 15213, USA
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20
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Differentiation of human adult-derived stem cells towards a neural lineage involves a dedifferentiation event prior to differentiation to neural phenotypes. Sci Rep 2021; 11:12034. [PMID: 34103613 PMCID: PMC8187441 DOI: 10.1038/s41598-021-91566-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 05/27/2021] [Indexed: 01/09/2023] Open
Abstract
Although it has been reported that mesenchymal stem cells isolated from adult tissues can be induced to overcome their mesenchymal fate and transdifferentiate into neural cells, the findings and their interpretation have been challenged. The main argument against this process is that the cells rapidly adopt neuron-like morphologies through retraction of the cytoplasm rather than active neurite extension. In this study, we examined the sequence of biological events during neural differentiation of human periodontal ligament-derived stem cells (hPDLSCs), human bone marrow-derived stem cells (hBMSCs) and human dental pulp-derived stem cells (hDPSCs) by time-lapse microscopy. We have demonstrated that hPDLSCs, hBMSCs and hDPSCs can directly differentiate into neuron-like cells without passing through a mitotic stage and that they shrink dramatically and change their morphology to that of neuron-like cells through active neurite extension. Furthermore, we observed micronuclei movement and transient cell nuclei lobulation concurrent to in vitro neurogenesis from hBMSCs and hDPSCs. Our results demonstrate that the differentiation of hPDLSCs, hBMSCs and hDPSCs towards a neural lineage occurs through a dedifferentiation step followed by differentiation to neural phenotypes, and therefore we definitively confirm that the rapid acquisition of the neural phenotype is via a differentiation trait.
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21
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Song W, Li S, Tang Q, Chen L, Yuan Z. In vitro biocompatibility and bioactivity of calcium silicate‑based bioceramics in endodontics (Review). Int J Mol Med 2021; 48:128. [PMID: 34013376 PMCID: PMC8136140 DOI: 10.3892/ijmm.2021.4961] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 03/19/2021] [Indexed: 12/26/2022] Open
Abstract
Calcium silicate-based bioceramics have been applied in endodontics as advantageous materials for years. In addition to excellent physical and chemical properties, the biocompatibility and bioactivity of calcium silicate-based bioceramics also serve an important role in endodontics according to previous research reports. Firstly, bioceramics affect cellular behavior of cells such as stem cells, osteoblasts, osteoclasts, fibroblasts and immune cells. On the other hand, cell reaction to bioceramics determines the effect of wound healing and tissue repair following bioceramics implantation. The aim of the present review was to provide an overview of calcium silicate-based bioceramics currently applied in endodontics, including mineral trioxide aggregate, Bioaggregate, Biodentine and iRoot, focusing on their in vitro biocompatibility and bioactivity. Understanding their underlying mechanism may help to ensure these materials are applied appropriately in endodontics.
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Affiliation(s)
- Wencheng Song
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Shue Li
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Qingming Tang
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Lili Chen
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Zhenglin Yuan
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
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22
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Comparative analysis of cytokines and growth factors in the conditioned media of stem cells from the pulp of deciduous, young, and old permanent tooth. Saudi J Biol Sci 2021; 28:3559-3565. [PMID: 34121899 PMCID: PMC8176054 DOI: 10.1016/j.sjbs.2021.03.031] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 03/04/2021] [Accepted: 03/08/2021] [Indexed: 02/08/2023] Open
Abstract
Objectives To compare and analyze the secretome profile of stem cells obtained from the deciduous tooth (SHEDs), young (yDPSCs), and old permanent tooth (oDPSCs). Methods All the stem cells were assessed for mesenchymal stem cell markers. The stem cells were differentiated into osteoblasts and chondrocytes using lineage-specific differentiation media. Conditioned media was collected from growing stem cells, and a cytometric bead array was performed to estimate secreted cytokines and growth factor levels by flow cytometry. Gene expresseion levels were assessed by real-time quantitative polymerase chain reaction. Results Age did not affect the mesenchymal characteristics of dental stem cells from various age groups. The secretomes of SHEDs and young yDPSCs exhibit more growth factors and lesser pro-inflammatory cytokines than oDPSCs. Osteo and chondrogenic differentiation potential were higher in SHEDs and young yDPSCs than in the oDPSCs. TLR1, TLR2, TLR3 show decreased expression levels with age and TLR5, TLR6 show increased expression with age. Conclusion The superior regenerative potential of SHEDs and yDPSCs may be due to the higher growth factors and lower pro-inflammatory cytokine profile.
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Masuda K, Han X, Kato H, Sato H, Zhang Y, Sun X, Hirofuji Y, Yamaza H, Yamada A, Fukumoto S. Dental Pulp-Derived Mesenchymal Stem Cells for Modeling Genetic Disorders. Int J Mol Sci 2021; 22:ijms22052269. [PMID: 33668763 PMCID: PMC7956585 DOI: 10.3390/ijms22052269] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 02/18/2021] [Accepted: 02/23/2021] [Indexed: 12/20/2022] Open
Abstract
A subpopulation of mesenchymal stem cells, developmentally derived from multipotent neural crest cells that form multiple facial tissues, resides within the dental pulp of human teeth. These stem cells show high proliferative capacity in vitro and are multipotent, including adipogenic, myogenic, osteogenic, chondrogenic, and neurogenic potential. Teeth containing viable cells are harvested via minimally invasive procedures, based on various clinical diagnoses, but then usually discarded as medical waste, indicating the relatively low ethical considerations to reuse these cells for medical applications. Previous studies have demonstrated that stem cells derived from healthy subjects are an excellent source for cell-based medicine, tissue regeneration, and bioengineering. Furthermore, stem cells donated by patients affected by genetic disorders can serve as in vitro models of disease-specific genetic variants, indicating additional applications of these stem cells with high plasticity. This review discusses the benefits, limitations, and perspectives of patient-derived dental pulp stem cells as alternatives that may complement other excellent, yet incomplete stem cell models, such as induced pluripotent stem cells, together with our recent data.
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Affiliation(s)
- Keiji Masuda
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812-8582, Japan; (X.H.); (H.S.); (Y.Z.); (X.S.); (Y.H.); (H.Y.)
- Correspondence: (K.M.); (S.F.); Tel.: +81-92-642-6402 (K.M. & S.F.)
| | - Xu Han
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812-8582, Japan; (X.H.); (H.S.); (Y.Z.); (X.S.); (Y.H.); (H.Y.)
| | - Hiroki Kato
- Department of Molecular Cell Biology and Oral Anatomy, Graduate School of Dental Science, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812-8582, Japan;
| | - Hiroshi Sato
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812-8582, Japan; (X.H.); (H.S.); (Y.Z.); (X.S.); (Y.H.); (H.Y.)
| | - Yu Zhang
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812-8582, Japan; (X.H.); (H.S.); (Y.Z.); (X.S.); (Y.H.); (H.Y.)
| | - Xiao Sun
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812-8582, Japan; (X.H.); (H.S.); (Y.Z.); (X.S.); (Y.H.); (H.Y.)
| | - Yuta Hirofuji
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812-8582, Japan; (X.H.); (H.S.); (Y.Z.); (X.S.); (Y.H.); (H.Y.)
| | - Haruyoshi Yamaza
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812-8582, Japan; (X.H.); (H.S.); (Y.Z.); (X.S.); (Y.H.); (H.Y.)
| | - Aya Yamada
- Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8577, Japan;
| | - Satoshi Fukumoto
- Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812-8582, Japan; (X.H.); (H.S.); (Y.Z.); (X.S.); (Y.H.); (H.Y.)
- Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8577, Japan;
- Correspondence: (K.M.); (S.F.); Tel.: +81-92-642-6402 (K.M. & S.F.)
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Potential Therapeutic Effects of Exosomes in Regenerative Endodontics. Arch Oral Biol 2020; 120:104946. [PMID: 33129129 DOI: 10.1016/j.archoralbio.2020.104946] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 09/07/2020] [Accepted: 10/04/2020] [Indexed: 02/05/2023]
Abstract
OBJECTIVE This review aims to describe the basic characteristics of exosomes, and summarize their possible source and potential biological effects in pulp regeneration, providing new insights into the therapeutic role of exosomes for regenerative endodontics in the future. DESIGN A comprehensive review of scientific literature related to exosomes potentially used for pulp regeneration was conducted. RESULTS Dental mesenchymal stem cells (MSCs) play an important role in dental pulp regeneration. MSC-derived exosomes, as important biotransmitters in intercellular communication, have been shown to replicate the therapeutic effects of their parental cells. These exosomes have better stability, lower immunogenicity, higher safety and clinical efficiency, making it possible to apply them in pulp regeneration. Existing research suggests that exosomes could trigger the regeneration of dentin/pulp-like tissue in vivo, which may attribute to their role in promoting pulp angiogenesis, regulating dental cell proliferation, migration and differentiation, and providing neuroprotection. CONCLUSIONS The applications of exosomes in the treatment of pulp regeneration have great potential, and exosomes may become ideal therapeutic biomaterial in regenerative endodontics.
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Mohan SP, Ramalingam M. Dental Pulp Stem Cells in Neuroregeneration. J Pharm Bioallied Sci 2020; 12:S60-S66. [PMID: 33149432 PMCID: PMC7595495 DOI: 10.4103/jpbs.jpbs_229_20] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 03/25/2020] [Accepted: 03/25/2020] [Indexed: 01/08/2023] Open
Abstract
Neurological diseases and injuries affect the routine life of patients. Current medical and surgical treatment has not improved the quality of life to desired limits. Neural regeneration through stem cells may be ideal choice in current scenario. Dental pulp stem cells (DPSCs), which are isolated from dental pulp, have shown excellent neuroregenerative properties in various animal studies. This review outlines the clinical perspective of DPSCs in neuroregeneration.
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Affiliation(s)
- Sunil Paramel Mohan
- Department of Oral and Maxillofacial Pathology, Sree Anjaneya Institute of Dental Sciences, Calicut, Kerala, India.,Department of Stems Cells and Regenerative Medicine, Malabar Medical College Hospital and Research Center, Calicut, Kerala, India
| | - Murugan Ramalingam
- Biomaterials and Organ Engineering Group, Centre for BioMaterials, Cellular and Molecular Theranostics, School of Mechanical Engineering, Vellore institute of Technology (Deemed to be University), Vellore, Tamil Nadu, India
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Rosaian AS, Rao GN, Mohan SP, Vijayarajan M, Prabhakaran RC, Sherwood A. Regenerative Capacity of Dental Pulp Stem Cells: A Systematic Review. JOURNAL OF PHARMACY AND BIOALLIED SCIENCES 2020; 12:S27-S36. [PMID: 33149427 PMCID: PMC7595477 DOI: 10.4103/jpbs.jpbs_121_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 03/06/2020] [Accepted: 03/13/2020] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVES The dental pulp contains undifferentiated mesenchymal cells, blood vessels and so on, which are responsible for routine functions of a tooth. The determination of stemness and regenerative properties using biomarkers and further application in routine practice may unravel its potential. MATERIALS AND METHODS Inclusion criteria-original research articles published in English, from 2000 to 2019, were collected both manually and by electronic search from databases of Cochrane, Medline, Embase, and PubMed. Exclusion criteria-articles other than English and review manuscripts were omitted. The shortlisted articles were reviewed for specific biomarkers, to assess the regenerative potential, stemness, and lineage of dental pulp stem cells. RESULTS Of 512 articles, 64 were selected and reviewed to determine the mesenchymal, neurogenic, vasculogenic, hematopoietic, and stem cell potential. On the basis of the search analysis, a panel of markers was proposed. CONCLUSION The application of proposed markers, on a pulpectomized tissue derived from human teeth, may be helpful to determine the regenerative potential and the usefulness in regenerative medicine and tissue engineering.
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Affiliation(s)
- Adlin S Rosaian
- Department of Oral and Maxillofacial Pathology and Oral Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
| | - Gururaj Narayana Rao
- Department of Oral and Maxillofacial Pathology and Oral Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
| | - Sunil P Mohan
- Department of Oral Pathology, Sree Anjaneya Institute of Dental Sciences, Kozhikode, Kerala, India
- Department of Stem Cells and Regenerative Medicine, Sree Anjaneya Institute of Dental Sciences, Kozhikode, Kerala, India
| | - Mahalakshmi Vijayarajan
- Department of Oral and Maxillofacial Pathology and Oral Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
| | - Rebekkah C Prabhakaran
- Department of Oral and Maxillofacial Pathology and Oral Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
| | - Anand Sherwood
- Department of Operative Dentistry and Endodontics, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
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Rosa M, Degregori E, Ferst J, Pillat M, Bertolin K, Souza J, Bello L, Pinto Filho S, Müller D. Isolamento e diferenciação das células-tronco da polpa dentária canina em células progenitoras neurais. ARQ BRAS MED VET ZOO 2019. [DOI: 10.1590/1678-4162-10672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
RESUMO O objetivo deste estudo foi verificar a capacidade de diferenciação das células-tronco da polpa dentária canina em células progenitoras neurais bem como quantificar obtenção e viabilidade celular, durante três passagens em cultura. As células foram extraídas da polpa dentária de dois cadáveres caninos, com aproximadamente dez meses de idade, que foram a óbito em decorrência de traumatismo automotivo. Após três subculturas, realizou-se avaliação da viabilidade celular por quantificação em câmara de Neubauer. A partir disso, induziu-se diferenciação neural em meio de cultura neurobasal (Gibco™), com células aderidas ao plástico ou suspensas em placas tratadas com agarose. Após sete e 14 dias em cultivo indutor, observou-se morfologia e perfil imunofenotípico utilizando citometria de fluxo e imunocitoquímica fluorescente. Aos 14 dias as células apresentaram alto grau de expressão para marcadores anti-nestina e anti-glial fibrillary acidic protein (anti-GFAP). Anteriormente, obteve-se ao 25º dia, média de 18x10⁶ células viáveis indiferenciadas oriundas do tecido pulpar. Sugere-se que as células-tronco indiferenciadas da polpa dentária canina apresentem índices satisfatórios de diferenciação em células progenitoras neurais, aderidas ou suspensas em cultura. A polpa dentária dos dentes decíduos caninos, fornece células indiferenciadas viáveis em quantidade adequada.
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Affiliation(s)
- M.P. Rosa
- Universidade Federal de Santa Maria, Brazil
| | | | - J.G. Ferst
- Universidade Federal de Santa Maria, Brazil
| | | | | | | | - L.K. Bello
- Universidade Federal de Santa Maria, Brazil
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Park YT, Lee SM, Kou X, Karabucak B. The Role of Interleukin 6 in Osteogenic and Neurogenic Differentiation Potentials of Dental Pulp Stem Cells. J Endod 2019; 45:1342-1348. [PMID: 31540748 DOI: 10.1016/j.joen.2019.08.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 07/04/2019] [Accepted: 08/06/2019] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Studies have shown that there is a significantly higher concentration of interleukin 6 (IL-6) in inflamed pulp tissues compared with healthy pulp tissues. The aims of this study were to investigate the baseline differences between mesenchymal stem cells (MSCs) isolated from healthy human dental pulp stem cells (H-DPSCs) and inflamed dental pulp stem cells (I-DPSCs) and their correlation to IL-6 and to determine whether IL-6 can affect the differentiation potentials of these cells. METHODS MSCs isolated from healthy and inflamed pulp tissues were cultured and characterized in vitro. The levels of secreted IL-6 in the culture supernatants from H-DPSCs and I-DPSCs were measured by enzyme-linked immunosorbent assay. IL-6 and neutralizing IL-6 were added to H-DPSCs and I-DPSCs, respectively. Immunofluorescence staining, alizarin red staining, and Western blotting were performed to assess the differentiation potentials of H-DPSCs and I-DPSCs. The independent unpaired 2-tailed Student's t-test was performed after quantification analysis. RESULTS H-DPSCs and I-DPSCs showed a similar expression of MSC-associated markers including CD44, CD73, CD90, and CD105, whereas H-DPSCs showed a lower level of IL-6, lower osteogenic differentiation potentials, and higher neurogenic differentiation potentials compared with I-DPSCs. The addition of IL-6 to H-DPSCs increased osteogenic potentials and decreased neurogenic potentials, whereas the neutralization of IL-6 for I-DPSCs led to decreased osteogenic potentials and increased neurogenic potentials. CONCLUSIONS The findings of this study indicated IL-6 has the capacity to enhance osteogenesis while hindering neurogenesis of DPSCs.
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Affiliation(s)
- Yong-Tae Park
- Department of Endodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Su-Min Lee
- Department of Endodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Xiaoxing Kou
- Guanghua School and Hospital of Stomatology, Southern China Center of Craniofacial Stem Cell Research, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Bekir Karabucak
- Department of Endodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Chuang YC, Yu Y, Wei MT, Chang CC, Ricotta V, Feng KC, Wang L, Bherwani AK, Ou-Yang HD, Simon M, Zhang L, Rafailovich M. Regulating substrate mechanics to achieve odontogenic differentiation for dental pulp stem cells on TiO 2 filled and unfilled polyisoprene. Acta Biomater 2019; 89:60-72. [PMID: 30836198 DOI: 10.1016/j.actbio.2019.02.040] [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] [Received: 11/07/2018] [Revised: 01/12/2019] [Accepted: 02/08/2019] [Indexed: 12/13/2022]
Abstract
We have shown that materials other than hydrogels commonly used in tissue engineering can be effective in enabling differentiation of dental pulp stem cells (DPSC). Here we demonstrate that a hydrophobic elastomer, polyisoprene (PI), a component of Gutta-percha, normally used to obturate the tooth canal, can also be used to initiate differentiation of the pulp. We showed that PI substrates without additional coating promote cell adhesion and differentiation, while their moduli can be easily adjusted either by varying the coating thickness or incorporation of inorganic particles. DPSC plated on those PI substrates were shown, using SPM and hysitron indentation, to adjust their moduli to conform to differentially small changes in the substrate modulus. In addition, optical tweezers were used to separately measure the membrane and cytoplasm moduli of DPSC, with and without Rho kinase inhibitor. The results indicated that the changes in modulus were attributed predominantly to changes within the cytoplasm, rather than the cell membrane. CLSM was used to identify cell morphology. Differentiation, as determined by qRT-PCR, of the upregulation of OCN, and COL1α1 as well as biomineralization, characterized by SEM/EDAX, was observed on hard PI substrates in the absence of induction factors, i.e. dexamethasone, with moduli 3-4 MPa, regardless of preparation. SEM showed that even though biomineralization was deposited on both spun cast thin PI and filled thick PI substrates, the minerals were aggregated into large clusters on thin PI, and uniformly distributed on filled thick PI, where it was templated within banded collagen fibers. STATEMENT OF SIGNIFICANCE: This manuscript demonstrates the potential of polyisoprene (PI), an elastomeric polymer, for use in tissue engineering. We show how dental pulp stem cells adjust their moduli continuously to match infinitesimally small changes in substrate mechanics, till a critical threshold is reached when they will differentiate. The lineage of differentiation then becomes a sensitive function of both mechanics and morphology for a given chemical composition. Since PI is a major component of Gutta-percha, the FDA approved material commonly used for obturating the root canal, this work suggests that it can easily be adapted for in vivo use in dental regeneration.
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30
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Lin W, Gao L, Jiang W, Niu C, Yuan K, Hu X, Ma R, Huang Z. The role of osteomodulin on osteo/odontogenic differentiation in human dental pulp stem cells. BMC Oral Health 2019; 19:22. [PMID: 30670012 PMCID: PMC6341608 DOI: 10.1186/s12903-018-0680-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Accepted: 11/27/2018] [Indexed: 01/09/2023] Open
Abstract
Background Extracellular matrix secretion and odontoblastic differentiation in human dental pulp stem cells (hDPSCs) are the cellular bases for reparative dentinogenesis. Osteomodulin (OMD) is a member of the small leucine-rich proteoglycan family distributed in the extracellular matrix but little is known about its role in osteo/odontogenic differentiation. The objective of this study was to investigate the role of OMD during osteo/odontoblastic differentiation of hDPSCs. Methods hDPSCs were selected using immune-magnetic beads and their capability of multi-differentiation was identified. OMD knockdown was achieved using short hairpin RNA (shRNA) lentivirus and was confirmed by western blot. Gene expression was measured by real-time qPCR and osteo/odontoblastic differentiation of hDPSCs was determined by alizarin red S staining. Results Compared with uninduced cells, the transcription of OMD was up-regulated by 35-fold at the late stage of osteo/odontogenic differentiation. shRNA-mediated gene silencing of OMD decreased the expression of odontoblastic genes, such as alkaline phosphatase (ALP), dentin matrix acidic phosphoprotein 1 (DMP1) and dentin sialophosphoprotein (DSPP). Besides, knockdown of OMD attenuated the mineralized nodules formation induced by osteo/odontogenic medium. Conclusions These results implied that OMD may play a pivotal role in modulating the osteo/odontoblastic differentiation of hDPSCs.
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Affiliation(s)
- Wenzhen Lin
- Department of Endodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Oral Diseases, Shanghai, China.,Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
| | - Li Gao
- Department of Endodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Oral Diseases, Shanghai, China.,Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
| | - Wenxin Jiang
- Department of Endodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Oral Diseases, Shanghai, China.,Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
| | - Chenguang Niu
- Department of Endodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Oral Diseases, Shanghai, China.,Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
| | - Keyong Yuan
- Department of Endodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Oral Diseases, Shanghai, China.,Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
| | - Xuchen Hu
- Department of Endodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Oral Diseases, Shanghai, China.,Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
| | - Rui Ma
- Department of Endodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. .,National Clinical Research Center for Oral Diseases, Shanghai, China. .,Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
| | - Zhengwei Huang
- Department of Endodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. .,National Clinical Research Center for Oral Diseases, Shanghai, China. .,Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
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Hosseini FS, Enderami SE, Hadian A, Abazari MF, Ardeshirylajimi A, Saburi E, Soleimanifar F, Nazemisalman B. Efficient osteogenic differentiation of the dental pulp stem cells on β‐glycerophosphate loaded polycaprolactone/polyethylene oxide blend nanofibers. J Cell Physiol 2019; 234:13951-13958. [DOI: 10.1002/jcp.28078] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 12/07/2018] [Indexed: 12/31/2022]
Affiliation(s)
| | - Seyedeh Elnaz Enderami
- Stem Cell and Regenerative Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering & Biotechnology (NIGEB) Tehran Iran
| | - Ali Hadian
- Stem Cell Technology Research Center Tehran Iran
| | - Mohammad Foad Abazari
- Department of Genetics Tehran Medical Science Branch, Islamic Azad University Tehran Iran
| | - Abdolreza Ardeshirylajimi
- Department of Tissue Engineering and Applied Cell Sciences School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences Tehran Iran
| | - Ehsan Saburi
- Clinical Research Development Center, Imam Hasan Hospital, North Khorasan University of Medical Sciences Bojnurd Iran
| | - Fatemeh Soleimanifar
- Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences Karaj Iran
| | - Bahareh Nazemisalman
- Department of Pediatrics Faculty of Dental, Zanjan University of Medical Sciences Zanjan Iran
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Dos Santos FP, Peruch T, Katami SJV, Martini APR, Crestani TA, Quintiliano K, Maurmann N, Sanches EF, Netto CA, Pranke P, de Souza Pagnussat A. Poly (lactide-co-glycolide) (PLGA) Scaffold Induces Short-term Nerve Regeneration and Functional Recovery Following Sciatic Nerve Transection in Rats. Neuroscience 2018; 396:94-107. [PMID: 30452974 DOI: 10.1016/j.neuroscience.2018.11.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 11/06/2018] [Accepted: 11/08/2018] [Indexed: 01/27/2023]
Abstract
Peripheral nerve injury is an important cause of incapability and has limited available treatment. Autologous donor nerve implant is the golden standard treatment, however, may cause secondary deficits. Stem cells show positive results in preclinical settings, preserving tissue and function. We tested the efficacy of stem cells derived from human exfoliated deciduous teeth seeded in poly (lactide-co-glycolide) scaffolds in sciatic nerve transection model. Seventy-two adult male Wistar rats had 7-mm nerve gap bridge using scaffolds with (or without) stem cells. Animals were randomly divided into: sham-operated; sham-operated without scaffold; sham-operated + scaffold + stem cells; sciatic transection + no treatment; sciatic transection + acellular scaffolds; sciatic transection + scaffold + stem cells. Sciatic Functional Index and Ladder Rung Walking tests were performed before (-1), 14 and 28 days after surgery. Morphometric nerve measurement and muscle weights were assessed. Scaffolds with stem cells improved function in Sciatic Functional Index. Acellular scaffold was effective, promoting functional recovery and nerve regeneration following nerve injury. Scaffolds provide better nerve regeneration and functional recovery after sciatic transection. Despite cell therapy promoting faster recovery after sciatic transection in the Sciatic Index Score, stem cells did not improve functional and morphological recovery after nerve injury. This is the first study testing the potential use of scaffolds combined with stem cells in the early stages after injury. Scaffolds with stem cells could accelerate nerve recovery and favor adjuvant therapies, evidencing the need for further studies to increase the knowledge about stem cells' mechanisms.
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Affiliation(s)
- Franciele Pereira Dos Santos
- Post-graduation Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | - Thais Peruch
- Department of Physical Therapy, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
| | | | - Ana Paula Rodrigues Martini
- Post-graduation Program in Neuroscience, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Thayane Antoniolli Crestani
- Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Post-graduation Program in Neuroscience, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Kerlin Quintiliano
- Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Post-graduation Program in Neuroscience, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Natasha Maurmann
- Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Post-graduation Program in Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Eduardo Farias Sanches
- Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Post-graduation Program in Neuroscience, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
| | - Carlos Alexandre Netto
- Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Patricia Pranke
- Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Post-graduation Program in Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Stem Cell Research Institute (SCRI), Porto Alegre, RS, Brazil
| | - Aline de Souza Pagnussat
- Post-graduation Program in Rehabilitation Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil; Department of Physical Therapy, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil; Post-graduation Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
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Ohkoshi S, Hirono H, Nakahara T, Ishikawa H. Dental pulp cell bank as a possible future source of individual hepatocytes. World J Hepatol 2018; 10:702-707. [PMID: 30386463 PMCID: PMC6206155 DOI: 10.4254/wjh.v10.i10.702] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Revised: 05/30/2018] [Accepted: 07/10/2018] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs) as a source for regenerative medicine are now the subject of much clinical attention. There are high expectations due to their safety, low tumorigenic risk, and low ethical concerns. MSC therapy has been approved for acute graft-versus host diseases since 2015. Tooth-derived MSCs are known to have a great potential in their proliferation and differentiation capacities, even when compared with bone-marrow-derived MSCs. In particular, stem cells from human exfoliated deciduous teeth (SHEDs) are the best candidates for personal cell banking (dental pulp cell bank), because they can be obtained less invasively in the natural process of individual growth. SHEDs are known to differentiate into hepatocytes. There have been several studies showing the effectiveness of SHEDs on the treatment of liver failure in animal models. They may exert their effects either by repopulation of cells in injured liver or by paracrine mechanisms due to their immune-regulatory functions. Moreover, it may be possible to use each individuals' dental pulp cells as a future source of tailor-made differentiated hepatocytes in the context of a bioartificial liver or liver-on-a-chip to screen for drug toxicity.
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Affiliation(s)
- Shogo Ohkoshi
- Department of Internal Medicine, School of Life Dentistry at Niigata, the Nippon Dental University, Niigata 951-8580, Japan.
| | - Haruka Hirono
- Department of Internal Medicine, School of Life Dentistry at Niigata, the Nippon Dental University, Niigata 951-8580, Japan
| | - Taka Nakahara
- Department of Developmental and Regenerative Dentistry, School of Life Dentistry at Tokyo, the Nippon Dental University, Chiyoda-ku 102-8159, Japan
| | - Hiroshi Ishikawa
- Laboratory of Clinical Regenerative Medicine, Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Laboratory of Advanced Research D #326, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
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Iezzi I, Cerqueni G, Licini C, Lucarini G, Mattioli Belmonte M. Dental pulp stem cells senescence and regenerative potential relationship. J Cell Physiol 2018; 234:7186-7197. [PMID: 30362542 DOI: 10.1002/jcp.27472] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 08/30/2018] [Indexed: 12/30/2022]
Abstract
Uncomplicated treatments for pulpitis and periodontitis continues to be challenging and regenerative approaches could meet this contingency. Dental pulp stem cells (DPSCs) represent a good candidate for oral recovering therapies. Here, we investigated changes in morphology, proliferation, and in vitro differentiation toward mesenchymal and neuronal phenotypes of human DPSCs harvested from differently aged donors. Aging is a physiologic phenomenon occurring with time that hamper body's capability to maintain homeostasis also affecting the functional reserve. Cytofluorimetric, immunohistochemical, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and western blot analyses were performed to gain insight for successful regenerative strategies in elderly. We observed a decline in DPSCs proliferation and differentiation potential with age. Interestingly, these cells behaved differently under osteogenic or odontogenic stimuli, showing different age-related mineralization capabilities. Similarly, neurogenic differentiation decreased with age. In conclusion, our observations represent a valid tool for the development of tailored regenerative strategies in an aging society.
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Affiliation(s)
- Iolanda Iezzi
- Department of Clinical and Molecular Sciences-DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
| | - Giorgia Cerqueni
- Department of Clinical and Molecular Sciences-DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
| | - Caterina Licini
- Department of Clinical and Molecular Sciences-DISCLIMO, Università Politecnica delle Marche, Ancona, Italy.,Department of Applied Science and Technology (DISAT), Polytechnic of Turin, Turin, Italy
| | - Guendalina Lucarini
- Department of Clinical and Molecular Sciences-DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
| | - Monica Mattioli Belmonte
- Department of Clinical and Molecular Sciences-DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
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35
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Yuan M, Zhan Y, Hu W, Li Y, Xie X, Miao N, Jin H, Zhang B. Aspirin promotes osteogenic differentiation of human dental pulp stem cells. Int J Mol Med 2018; 42:1967-1976. [PMID: 30085338 PMCID: PMC6108875 DOI: 10.3892/ijmm.2018.3801] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 07/30/2018] [Indexed: 12/19/2022] Open
Abstract
Human dental pulp stem cells (hDPSCs) possess self‑renewal and osteogenic differentiation properties, and have been used for orofacial bone regeneration and periodontal treatment. Aspirin has been demonstrated to enhance the regeneration of bone marrow mesenchymal stem cells (MSCs); however, the impact of aspirin on the osteogenic differentiation of hDPSCs remains unknown. In the present study, hDPSCs were characterized by flow cytometry, while their clonogenic potential and multipotency were assessed using alizarin red, Oil red O and alcian blue staining. The effect of aspirin on hDPSC viability was assessed using Cell Counting Kit‑8 assay. Osteogenic capacity was examined by alkaline phosphatase activity, alizarin red staining, reverse transcription‑polymerase chain reaction and western blotting. Furthermore, in vivo cranial defects were established in Sprague‑Dawley rats to evaluate the effect of aspirin on hDPSC‑based bone regeneration. Anorganic bovine bone was used as a bone replacement material and as the carrier for hDPSCs. New bone formation was observed through radiographic and histological analysis. The study demonstrated that hDPSCs expressed MSC markers and possessed multipotency in vitro. Aspirin was non‑toxic to hDPSCs at a concentration of ≤100 µg/ml and enhanced the osteogenesis of hDPSCs in vitro. Aspirin significantly increased hDPSC‑based bone formation in the rat cranial defect model at 8 or 12 weeks post‑implantation (P<0.05). The data suggested that aspirin promotes the osteogenic potential of hDPSCs in vitro and in vivo. Overall, the present study indicated that aspirin improves the bone regeneration capacity of hDPSCs.
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Affiliation(s)
- Mengtong Yuan
- Department of Prosthodontics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Yuanbo Zhan
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Weiping Hu
- Department of Prosthodontics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Ying Li
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Xiaohua Xie
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Nan Miao
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Han Jin
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Bin Zhang
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
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36
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Fujii S, Fujimoto K, Goto N, Abiko Y, Imaoka A, Shao J, Kitayama K, Kanawa M, Sosiawan A, Suardita K, Nishimura F, Kato Y. Characterization of human dental pulp cells grown in chemically defined serum-free medium. Biomed Rep 2018; 8:350-358. [PMID: 29556382 PMCID: PMC5844140 DOI: 10.3892/br.2018.1066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 02/08/2018] [Indexed: 01/09/2023] Open
Abstract
Dental pulp cells (DPCs) are promising candidates for use as transplantable cells in regenerative medicine. However, ex vivo expansion of these cells typically requires culture media containing fetal bovine serum, which may cause infection and immunological reaction following transplantation. In addition, the proliferation and differentiation of DPCs markedly depend upon serum batches. Therefore, the present study examined whether DPCs could be expanded under serum-free conditions. DPCs obtained from four donors were identified to proliferate actively in the serum-free medium, STK2, when compared with those cells in control medium (Dulbecco's modified Eagle's medium containing 10% serum). The high proliferative potential with STK2 was maintained through multiple successive culture passages. DNA microarray analyses demonstrated that the gene expression profile of DPCs grown in STK2 was similar to that of cells grown in the control medium; however, a number of genes related to cell proliferation, including placental growth factor and inhibin-βE, were upregulated in the STK2 cultures. Following induction of osteogenesis, DPCs grown in STK2 induced alkaline phosphatase activity and calcification at higher levels compared with the control medium cultures, indicating maintenance of differentiation potential in STK2. This serum-free culture system with DPCs may have applications in further experimental studies and as a clinical strategy in regenerative medicine.
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Affiliation(s)
- Sakiko Fujii
- Department of Dental Science for Health Promotion, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
| | - Katsumi Fujimoto
- Department of Dental and Medical Biochemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.,Department of Molecular Biology and Biochemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
| | - Noriko Goto
- Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
| | - Yoshimitsu Abiko
- Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan
| | - Asayo Imaoka
- Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan
| | | | - Kazuko Kitayama
- Department of Dental and Medical Biochemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
| | - Masami Kanawa
- Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima 734-8553, Japan
| | - Agung Sosiawan
- Department of Dental Public Health, Faculty of Dental Medicine, Airlangga University, Surabaya, East Java 60132, Indonesia
| | - Ketut Suardita
- Department of Conservative Dentistry, Faculty of Dental Medicine, Airlangga University, Surabaya, East Java 60132, Indonesia
| | - Fusanori Nishimura
- Department of Dental Science for Health Promotion, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
| | - Yukio Kato
- Department of Dental and Medical Biochemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.,Two Cells Co., Ltd., Hiroshima 734-0816, Japan
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Datko Williams L, Farley A, Cupelli M, Alapati S, Kennedy MS, Dean D. Effects of substrate stiffness on dental pulp stromal cells in culture. J Biomed Mater Res A 2018; 106:1789-1797. [PMID: 29468814 DOI: 10.1002/jbm.a.36382] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 02/07/2018] [Accepted: 02/09/2018] [Indexed: 12/19/2022]
Abstract
Dental pulp stromal cells (DPSCs) can be differentiated down lineages known to either express bone or dentin specific protein markers. Since the differentiation of cells can be heavily influenced by their environment, it may be possible to influence the osteogenic/odontogenic potential of DPSCs by modulating the mechanical properties of substrate on which they are grown. In this study, human DPSCs were grown with and without hydroxyapatite (HA) microparticles on a range of substrates including fibronectin-coated hydrogels and glass substrates, which represented an elastic moduli range of approximately 3 kPa-50 GPa, over a 21-day period. Alkaline phosphatase activity, osteopontin production, and mineralization were monitored. The presence of HA microparticles increased the relative degree of mineralized matrix produced by the cells relative to those in the same substrate and media condition without the HA microparticles. In addition, cultures with cells grown on stiffer substrates had higher ALP activity and higher degree of mineralization than those grown on softer substrates. This study shows that DPSCs are affected by the mechanical properties of their underlying growth substrate and by the presence of HA microparticles. In addition, relatively stiff substrates (>75 kPa) may be required for significant mineralization of these cultures. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1789-1797, 2018.
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Affiliation(s)
| | - Amanda Farley
- Bioengineering Department, Clemson University, Clemson, South Carolina, 29634
| | - Matthew Cupelli
- Bioengineering Department, Clemson University, Clemson, South Carolina, 29634
| | - Satish Alapati
- Department of Endodontics, University of Illinois at Chicago, Chicago, Illinois, 60612
| | - Marian S Kennedy
- Department of Materials Science and Engineering, Clemson University, Clemson, South Carolina, 29634
| | - Delphine Dean
- Bioengineering Department, Clemson University, Clemson, South Carolina, 29634
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38
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Williams MA, Biguetti C, Romero-Bustillos M, Maheshwari K, Dinckan N, Cavalla F, Liu X, Silva R, Akyalcin S, Uyguner ZO, Vieira AR, Amendt BA, Fakhouri WD, Letra A. Colorectal Cancer-Associated Genes Are Associated with Tooth Agenesis and May Have a Role in Tooth Development. Sci Rep 2018; 8:2979. [PMID: 29445242 PMCID: PMC5813178 DOI: 10.1038/s41598-018-21368-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2017] [Accepted: 02/01/2018] [Indexed: 12/25/2022] Open
Abstract
Previously reported co-occurrence of colorectal cancer (CRC) and tooth agenesis (TA) and the overlap in disease-associated gene variants suggest involvement of similar molecular pathways. Here, we took an unbiased approach and tested genome-wide significant CRC-associated variants for association with isolated TA. Thirty single nucleotide variants (SNVs) in CRC-predisposing genes/loci were genotyped in a discovery dataset composed of 440 individuals with and without isolated TA. Genome-wide significant associations were found between TA and ATF1 rs11169552 (P = 4.36 × 10-10) and DUSP10 rs6687758 (P = 1.25 × 10-9), and positive association found with CASC8 rs10505477 (P = 8.2 × 10-5). Additional CRC marker haplotypes were also significantly associated with TA. Genotyping an independent dataset consisting of 52 cases with TA and 427 controls confirmed the association with CASC8. Atf1 and Dusp10 expression was detected in the mouse developing teeth from early bud stages to the formation of the complete tooth, suggesting a potential role for these genes and their encoded proteins in tooth development. While their individual contributions in tooth development remain to be elucidated, these genes may be considered candidates to be tested in additional populations.
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Affiliation(s)
- Meredith A Williams
- Center for Craniofacial Research, University of Texas Health Science Center School of Dentistry, Houston, 77054, USA
| | - Claudia Biguetti
- Center for Craniofacial Research, University of Texas Health Science Center School of Dentistry, Houston, 77054, USA
- Department of Biological Sciences, University of Sao Paulo Bauru Dental School, Bauru, 17012, Brazil
| | - Miguel Romero-Bustillos
- Iowa Institute for Oral Health, College of Dentistry, University of Iowa, Iowa City, 52242, USA
| | - Kanwal Maheshwari
- Center for Craniofacial Research, University of Texas Health Science Center School of Dentistry, Houston, 77054, USA
| | - Nuriye Dinckan
- Center for Craniofacial Research, University of Texas Health Science Center School of Dentistry, Houston, 77054, USA
- Department of Medical Genetics, School of Medicine, Istanbul University, Istanbul, 34093, Turkey
| | - Franco Cavalla
- Center for Craniofacial Research, University of Texas Health Science Center School of Dentistry, Houston, 77054, USA
- Department of Biological Sciences, University of Sao Paulo Bauru Dental School, Bauru, 17012, Brazil
| | - Xiaoming Liu
- Department of Epidemiology and Human Genetics, University of Texas Health Science Center School of Public Health, Houston, 77054, USA
| | - Renato Silva
- Center for Craniofacial Research, University of Texas Health Science Center School of Dentistry, Houston, 77054, USA
- Department of Endodontics, University of Texas Health Science Center School of Dentistry, Houston, 77054, USA
- Pediatric Research Center, University of Texas Health Science Center McGovern Medical School, Houston, 77054, USA
| | - Sercan Akyalcin
- Department of Orthodontics, Tufts University, Boston, 02111, USA
| | - Z Oya Uyguner
- Department of Medical Genetics, School of Medicine, Istanbul University, Istanbul, 34093, Turkey
| | - Alexandre R Vieira
- Departments of Oral Biology and Pediatric Dentistry, University of Pittsburgh School of Dental Medicine, Pittsburgh, 15229, USA
| | - Brad A Amendt
- Iowa Institute for Oral Health, College of Dentistry, University of Iowa, Iowa City, 52242, USA
- Craniofacial Anomalies Research Center, Carver College of Medicine, University of Iowa, Iowa City, 52242, USA
| | - Walid D Fakhouri
- Center for Craniofacial Research, University of Texas Health Science Center School of Dentistry, Houston, 77054, USA
- Pediatric Research Center, University of Texas Health Science Center McGovern Medical School, Houston, 77054, USA
- Department of Diagnostic and Biomedical Sciences, Sciences University of Texas Health Science Center School of Dentistry, Houston, 77054, USA
| | - Ariadne Letra
- Center for Craniofacial Research, University of Texas Health Science Center School of Dentistry, Houston, 77054, USA.
- Pediatric Research Center, University of Texas Health Science Center McGovern Medical School, Houston, 77054, USA.
- Department of Diagnostic and Biomedical Sciences, Sciences University of Texas Health Science Center School of Dentistry, Houston, 77054, USA.
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39
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Donders R, Bogie JF, Ravanidis S, Gervois P, Vanheusden M, Marée R, Schrynemackers M, Smeets HJ, Pinxteren J, Gijbels K, Walbers S, Mays RW, Deans R, Van Den Bosch L, Stinissen P, Lambrichts I, Gyselaers W, Hellings N. Human Wharton's Jelly-Derived Stem Cells Display a Distinct Immunomodulatory and Proregenerative Transcriptional Signature Compared to Bone Marrow-Derived Stem Cells. Stem Cells Dev 2018; 27:65-84. [DOI: 10.1089/scd.2017.0029] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Affiliation(s)
- Raf Donders
- Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - Jeroen F.J. Bogie
- Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | | | - Pascal Gervois
- Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - Marjan Vanheusden
- Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - Raphaël Marée
- University of Liège, GIGA Bioinformatics Core Facility, Liège, Belgium
| | | | - Hubert J.M. Smeets
- Maastricht UMC+, Department of Genetics and Cell Biology, Research School GROW and CARIM, Maastricht, the Netherlands
| | - Jef Pinxteren
- ReGenesys BVBA, Bio-Incubator Leuven, Heverlee, Belgium
| | | | - Sara Walbers
- ReGenesys BVBA, Bio-Incubator Leuven, Heverlee, Belgium
| | - Robert W. Mays
- Department of Regenerative Medicine, Athersys, Inc., Cleveland, Ohio
| | - Robert Deans
- Department of Regenerative Medicine, Athersys, Inc., Cleveland, Ohio
| | - Ludo Van Den Bosch
- KU Leuven, Laboratory of Neurobiology, Experimental Neurology and VIB, Center for Brain & Disease, Leuven, Belgium
| | - Piet Stinissen
- Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - Ivo Lambrichts
- Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - Wilfried Gyselaers
- Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
- Ziekenhuis Oost-Limburg, Campus St. Jan, Genk, Belgium
| | - Niels Hellings
- Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
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40
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Xiao N, Yu WY, Liu D. Glial cell‐derived neurotrophic factor promotes dental pulp stem cell migration. J Tissue Eng Regen Med 2017; 12:705-714. [DOI: 10.1002/term.2490] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 04/27/2017] [Accepted: 06/01/2017] [Indexed: 12/23/2022]
Affiliation(s)
- Nan Xiao
- Department of Biomedical Sciences, Arthur A. Dugoni School of DentistryUniversity of the Pacific San Francisco CA USA
| | - Wei Ye Yu
- Department of Biomedical Sciences, Arthur A. Dugoni School of DentistryUniversity of the Pacific San Francisco CA USA
| | - Dawei Liu
- Department of Anatomy and Cell Biology, School of Dental MedicineUniversity of the Pennsylvania Philadelphia PA USA
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41
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Mortada I, Mortada R, Al Bazzal M. Dental pulp stem cells and the management of neurological diseases: An update. J Neurosci Res 2017; 96:265-272. [PMID: 28736906 DOI: 10.1002/jnr.24122] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 07/05/2017] [Accepted: 07/05/2017] [Indexed: 01/08/2023]
Abstract
Medical research in regenerative medicine has brought promising perspectives for the use of stem cells in clinical trials. Stem cells are undifferentiated cells capable of multilineage differentiation and available in numerous sources in the human body. Dental pulp constitutes an attractive source of these cells since collecting mesenchymal stem cells from this site is a noninvasive practice that can be performed after a common surgical extraction of supernumerary or wisdom teeth. Thus, tissue sacrifice is very low and several cytotypes can be obtained owing to these cells' multipotency, in addition to the fact that they can be cryopreserved and stored for long periods. Mesenchymal stem cells have high proliferation rates, making them favorable for clinical application. These multipotent cells, present in biological waste, constitute an appropriate resource in the treatment of many neurological diseases.
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Affiliation(s)
- Ibrahim Mortada
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Rola Mortada
- Lebanese University School of Dentistry, Beirut, Lebanon
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42
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Yasui T, Mabuchi Y, Morikawa S, Onizawa K, Akazawa C, Nakagawa T, Okano H, Matsuzaki Y. Isolation of dental pulp stem cells with high osteogenic potential. Inflamm Regen 2017; 37:8. [PMID: 29259707 PMCID: PMC5725894 DOI: 10.1186/s41232-017-0039-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Accepted: 02/23/2017] [Indexed: 01/05/2023] Open
Abstract
Dental pulp stem cells/progenitor cells (DPSCs) can be easily obtained and can have excellent proliferative and mineralization potentials. Therefore, many studies have investigated the isolation and bone formation of DPSCs. In most previous reports, human DPSCs were traditionally isolated by exploiting their ability to adhere to plastic tissue culture dishes. DPSCs isolated by plastic adherence are frequently contaminated by other cells, which limits the ability to investigate their basic biology and regenerative properties. Additionally, the proliferative and osteogenic potentials vary depending on the isolated cells. It is very difficult to obtain cells of a sufficient quality to elicit the required effect upon transplantation. Considering clinical applications, stem cells used for regenerative medicine need to be purified in order to increase the efficiency of bone regeneration, and a stable supply of these cells must be generated. Here, we review the purification of DPSCs and studies of cranio-maxillofacial bone regeneration using these cells. Additionally, we introduce the prospective isolation of DPSCs using specific cell surface markers: low-affinity nerve growth factor and thymocyte antigen 1.
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Affiliation(s)
- Takazumi Yasui
- Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan.,Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan.,Department of Dentistry and Oral Surgery, Kawasaki Municipal Kawasaki Hospital, 12-1 Shinkawadori, Kawasaki-ku, Kawasaki, Kanagawa 210-0013 Japan
| | - Yo Mabuchi
- Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan.,Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510 Japan
| | - Satoru Morikawa
- Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan
| | - Katsuhiro Onizawa
- Department of Dentistry and Oral Surgery, Kawasaki Municipal Kawasaki Hospital, 12-1 Shinkawadori, Kawasaki-ku, Kawasaki, Kanagawa 210-0013 Japan
| | - Chihiro Akazawa
- Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510 Japan
| | - Taneaki Nakagawa
- Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan
| | - Hideyuki Okano
- Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan
| | - Yumi Matsuzaki
- Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan.,Department of Cancer Biology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, Shimane 693-8501 Japan
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43
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Ohkoshi S, Hara H, Hirono H, Watanabe K, Hasegawa K. Regenerative medicine using dental pulp stem cells for liver diseases. World J Gastrointest Pharmacol Ther 2017; 8:1-6. [PMID: 28217369 PMCID: PMC5292602 DOI: 10.4292/wjgpt.v8.i1.1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Revised: 11/16/2016] [Accepted: 12/16/2016] [Indexed: 02/06/2023] Open
Abstract
Acute liver failure is a refractory disease and its prognosis, if not treated using liver transplantation, is extremely poor. It is a good candidate for regenerative medicine, where stem cell-based therapies play a central role. Mesenchymal stem cells (MSCs) are known to differentiate into multiple cell lineages including hepatocytes. Autologous cell transplant without any foreign gene induction is feasible using MSCs, thereby avoiding possible risks of tumorigenesis and immune rejection. Dental pulp also contains an MSC population that differentiates into hepatocytes. A point worthy of special mention is that dental pulp can be obtained from deciduous teeth during childhood and can be subsequently harvested when necessary after deposition in a tooth bank. MSCs have not only a regenerative capacity but also act in an anti-inflammatory manner via paracrine mechanisms. Promising efficacies and difficulties with the use of MSC derived from teeth are summarized in this review.
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44
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Dental Pulp Stem Cells and Neurogenesis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 1083:63-75. [DOI: 10.1007/5584_2017_71] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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45
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Huang CC, Narayanan R, Alapati S, Ravindran S. Exosomes as biomimetic tools for stem cell differentiation: Applications in dental pulp tissue regeneration. Biomaterials 2016; 111:103-115. [PMID: 27728810 DOI: 10.1016/j.biomaterials.2016.09.029] [Citation(s) in RCA: 229] [Impact Index Per Article: 25.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 09/22/2016] [Accepted: 09/30/2016] [Indexed: 01/11/2023]
Abstract
Achieving and maintaining safe and reliable lineage specific differentiation of stem cells is important for clinical translation of tissue engineering strategies. In an effort to circumvent the multitude of problems arising from the usage of growth factors and growth factor delivery systems, we have explored the use of exosomes as biomimetic tools to induce stem cell differentiation. Working on the hypothesis that cell-type specific exosomes can trigger lineage-specific differentiation of stem cells, we have evaluated the potential of exosomes derived from dental pulp cells cultured on under growth and odontogenic differentiation conditions to induce odontogenic differentiation of naïve human dental pulp stem cells (DPSCs) and human bone marrow derived stromal cells (HMSCs) in vitro and in vivo. Results indicate that the exosomes can bind to matrix proteins such as type I collagen and fibronectin enabling them to be tethered to biomaterials. The exosomes are endocytosed by both DPSCs and HMSCs in a dose-dependent and saturable manner via the caveolar endocytic mechanism and trigger the P38 mitogen activated protein kinase (MAPK) pathway. In addition, the exosomes also trigger the increased expression of genes required for odontogenic differentiation. When tested in vivo in a tooth root slice model with DPSCs, the exosomes triggered regeneration of dental pulp-like tissue. However, our results indicate that exosomes isolated under odontogenic conditions are better inducers of stem cell differentiation and tissue regeneration. Overall, our results highlight the potential exosomes as biomimetic tools to induce lineage specific differentiation of stem cells. Our results also show the importance of considering the source and state of exosome donor cells before a choice is made for therapeutic applications.
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Affiliation(s)
- Chun-Chieh Huang
- Department of Oral Biology, University of Illinois at Chicago, USA
| | | | - Satish Alapati
- Department of Endodontics, University of Illinois at Chicago, USA
| | - Sriram Ravindran
- Department of Oral Biology, University of Illinois at Chicago, USA.
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46
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Kaushik SN, Kim B, Walma AMC, Choi SC, Wu H, Mao JJ, Jun HW, Cheon K. Biomimetic microenvironments for regenerative endodontics. Biomater Res 2016; 20:14. [PMID: 27257508 PMCID: PMC4890532 DOI: 10.1186/s40824-016-0061-7] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 05/24/2016] [Indexed: 12/16/2022] Open
Abstract
Regenerative endodontics has been proposed to replace damaged and underdeveloped tooth structures with normal pulp-dentin tissue by providing a natural extracellular matrix (ECM) mimicking environment; stem cells, signaling molecules, and scaffolds. In addition, clinical success of the regenerative endodontic treatments can be evidenced by absence of signs and symptoms; no bony pathology, a disinfected pulp, and the maturation of root dentin in length and thickness. In spite of the various approaches of regenerative endodontics, there are several major challenges that remain to be improved: a) the endodontic root canal is a strong harbor of the endodontic bacterial biofilm and the fundamental etiologic factors of recurrent endodontic diseases, (b) tooth discolorations are caused by antibiotics and filling materials, (c) cervical root fractures are caused by endodontic medicaments, (d) pulp tissue is not vascularized nor innervated, and (e) the dentin matrix is not developed with adequate root thickness and length. Generally, current clinical protocols and recent studies have shown a limited success of the pulp-dentin tissue regeneration. Throughout the various approaches, the construction of biomimetic microenvironments of pulp-dentin tissue is a key concept of the tissue engineering based regenerative endodontics. The biomimetic microenvironments are composed of a synthetic nano-scaled polymeric fiber structure that mimics native pulp ECM and functions as a scaffold of the pulp-dentin tissue complex. They will provide a framework of the pulp ECM, can deliver selective bioactive molecules, and may recruit pluripotent stem cells from the vicinity of the pulp apex. The polymeric nanofibers are produced by methods of self-assembly, electrospinning, and phase separation. In order to be applied to biomedical use, the polymeric nanofibers require biocompatibility, stability, and biodegradability. Therefore, this review focuses on the development and application of the biomimetic microenvironments of pulp-dentin tissue among the current regenerative endodontics.
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Affiliation(s)
- Sagar N Kaushik
- Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, USA
| | - Bogeun Kim
- Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, USA
| | - Alexander M Cruz Walma
- Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, USA
| | - Sung Chul Choi
- Department of Pediatric Dentistry, Kyung Hee University, Seoul, South Korea
| | - Hui Wu
- Department of Pediatric Dentistry, University of Alabama at Birmingham, SDB 311, 1720 2nd Ave South, Birmingham, AL 35294-0007 USA
| | - Jeremy J Mao
- Center for Craniofacial Regeneration at Columbia University, New York City, NY USA
| | - Ho-Wook Jun
- Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, USA
| | - Kyounga Cheon
- Department of Pediatric Dentistry, University of Alabama at Birmingham, SDB 311, 1720 2nd Ave South, Birmingham, AL 35294-0007 USA
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Yu W, Zhang Y, Jiang C, He W, Yi Y, Wang J. Orthodontic treatment mediates dental pulp microenvironment via IL17A. Arch Oral Biol 2016; 66:22-9. [DOI: 10.1016/j.archoralbio.2016.01.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2015] [Revised: 12/22/2015] [Accepted: 01/19/2016] [Indexed: 01/04/2023]
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48
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Using Stem Cells to Grow Artificial Tissue for Peripheral Nerve Repair. Stem Cells Int 2016; 2016:7502178. [PMID: 27212954 PMCID: PMC4861803 DOI: 10.1155/2016/7502178] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Revised: 02/17/2016] [Accepted: 03/02/2016] [Indexed: 12/17/2022] Open
Abstract
Peripheral nerve injury continues to pose a clinical hurdle despite its frequency and advances in treatment. Unlike the central nervous system, neurons of the peripheral nervous system have a greater ability to regenerate. However, due to a number of confounding factors, this is often both incomplete and inadequate. The lack of supportive Schwann cells or their inability to maintain a regenerative phenotype is a major factor. Advances in nervous system tissue engineering technology have led to efforts to build Schwann cell scaffolds to overcome this and enhance the regenerative capacity of neurons following injury. Stem cells that can differentiate along a neural lineage represent an essential resource and starting material for this process. In this review, we discuss the different stem cell types that are showing promise for nervous system tissue engineering in the context of peripheral nerve injury. We also discuss some of the biological, practical, ethical, and commercial considerations in using these different stem cells for future clinical application.
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Kushnerev E, Shawcross S, Hillarby M, Yates J. High-plasticity mesenchymal stem cells isolated from adult-retained primary teeth and autogenous adult tooth pulp—A potential source for regenerative therapies? Arch Oral Biol 2016; 62:43-8. [DOI: 10.1016/j.archoralbio.2015.11.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Revised: 08/21/2015] [Accepted: 11/13/2015] [Indexed: 01/09/2023]
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50
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Liu C, Xiong H, Chen K, Huang Y, Huang Y, Yin X. Long-term exposure to pro-inflammatory cytokines inhibits the osteogenic/dentinogenic differentiation of stem cells from the apical papilla. Int Endod J 2015; 49:950-9. [DOI: 10.1111/iej.12551] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Accepted: 09/11/2015] [Indexed: 12/11/2022]
Affiliation(s)
- C. Liu
- Department of Stomatology; Guangzhou Women and Children's Medical Center; Guangzhou Medical University; Guangzhou China
| | - H. Xiong
- Department of Stomatology; Guangzhou Women and Children's Medical Center; Guangzhou Medical University; Guangzhou China
| | - K. Chen
- Department of Stomatology; Guangzhou Women and Children's Medical Center; Guangzhou Medical University; Guangzhou China
| | - Y. Huang
- Department of Stomatology; Guangzhou Women and Children's Medical Center; Guangzhou Medical University; Guangzhou China
| | - Y. Huang
- Department of Stomatology; Guangzhou Women and Children's Medical Center; Guangzhou Medical University; Guangzhou China
| | - X. Yin
- Department of Stomatology; Guangzhou Women and Children's Medical Center; Guangzhou Medical University; Guangzhou China
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