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Iwasaki A, Hatakeyama M, Liu Q, Orimoto A, Fukuda T, Kitaoka T. Proliferation and differentiation of human dental pulp stem cells on phosphorylated cellulose nanofiber scaffolds. Carbohydr Polym 2025; 359:123593. [PMID: 40306767 DOI: 10.1016/j.carbpol.2025.123593] [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: 01/08/2025] [Revised: 04/02/2025] [Accepted: 04/07/2025] [Indexed: 05/02/2025]
Abstract
Human dental pulp stem cells (hDPSCs) are a promising cell source for tooth regeneration therapies. However, conventional culture scaffold materials are often animal-derived, leading to immunogenicity concerns and limited availability. In this study, we explored phosphorylated cellulose nanofibers (P-CNFs), which have a fine fiber morphology and phosphate groups, as a novel scaffold material for cell culture. Immortalized hDPSCs were cultured on P-CNF scaffolds with different phosphate contents (0-1.42 mmol g-1) prepared by varying the molar ratio of urea and diammonium hydrogen phosphate and the reaction time. Cells cultured on unmodified CNFs exhibited poor adhesion and formed spheroids, indicating low bioadaptability. In contrast, P-CNF scaffolds with moderate phosphate content (0.54-0.78 mmol g-1) significantly improved cell adhesion; further increases in phosphate content decreased cell adhesion, indicating a strong dependence on phosphate content. Intriguingly, even in the absence of differentiation inducers, hDPSCs on P-CNF scaffolds with an optimal phosphate content of 0.78 mmol g-1 showed equal or higher expression of hard tissue marker genes compared to collagen scaffolds with differentiation inducers, suggesting that P-CNFs can directly promote hard tissue differentiation. These findings highlight plant-derived, animal-free P-CNFs as a promising biomaterial for advanced dental tissue engineering.
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Affiliation(s)
- Akihiro Iwasaki
- Department of Agro-Environmental Sciences, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan
| | - Mayumi Hatakeyama
- Department of Agro-Environmental Sciences, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan
| | - Qimei Liu
- Department of Agro-Environmental Sciences, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan
| | - Ai Orimoto
- Division of Endodontics and Restorative Dentistry, Kyushu Dental University, Kitakyushu 803-8580, Japan
| | - Tomokazu Fukuda
- Graduate School of Science and Engineering, Iwate University, Morioka, Iwate 020-8551, Japan
| | - Takuya Kitaoka
- Department of Agro-Environmental Sciences, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan.
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2
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Wang J, Yang F, Chen R, Yang X, Wang J, Zhang H. Hydrogel Composite Incorporating Deferoxamine-Loaded Gelatin-Based Microspheres Enhance Angiogenesis Ability of Dental Pulp Stem Cells. ACS OMEGA 2025; 10:12579-12589. [PMID: 40191326 PMCID: PMC11966253 DOI: 10.1021/acsomega.5c00445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 03/03/2025] [Accepted: 03/14/2025] [Indexed: 04/09/2025]
Abstract
Fast reconstruction of the pulpal vasculature is crucial for effective pulp regeneration. Dental pulp stem cells (DPSCs) are promising candidates for pulp regeneration because of their potential for multilineage differentiation and vasculogenic properties. Deferoxamine (DFO) has been shown to stimulate angiogenesis during wound healing and bone regeneration; however, the effects of DFO on the angiogenic potential of DPSCs remain unknown. Moreover, its usefulness is restricted by a limited half-life and challenges in achieving localized tissue enrichment. This study aimed to develop a sustained-release injectable hydrogel composite as a drug delivery system and to investigate its influence on DPSCs. Herein, gelatin-based microspheres (GMSs) were loaded with DFO, and temperature-sensitive injectable hydrogels incorporating collagen and chitosan were synthesized to enable controlled DFO release. The experimental findings demonstrated that the DFO-loaded GMSs (DFO-GMSs) hydrogel composite possessed favorable physical properties and biocompatibility, enabling sustained DFO delivery for up to 15 days. DFO effectively stimulated DPSC migration, promoted the secretion of angiogenesis-related factors, and induced tube formation in vitro. These results suggest that the DFO-GMSs hydrogel composite significantly increased the migration and angiogenic potential of DPSCs, highlighting its promise for tissue regeneration applications.
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Affiliation(s)
- Jie Wang
- College
and Hospital of Stomatology, Anhui Medical
University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei230032, China
| | - Fan Yang
- College
and Hospital of Stomatology, Anhui Medical
University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei230032, China
| | - Ruting Chen
- College
and Hospital of Stomatology, Anhui Medical
University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei230032, China
- Department
of Stomatology, Yangjiang People’s
Hospital, Affiliated Yangjiang Hospital of Guangdong Medical University, Yangjiang529500, China
| | - Xinyue Yang
- College
and Hospital of Stomatology, Anhui Medical
University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei230032, China
| | - Jingjing Wang
- College
and Hospital of Stomatology, Anhui Medical
University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei230032, China
| | - Hongyan Zhang
- College
and Hospital of Stomatology, Anhui Medical
University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei230032, China
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3
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Su W, Liao C, Liu X. Angiogenic and neurogenic potential of dental-derived stem cells for functional pulp regeneration: A narrative review. Int Endod J 2025; 58:391-410. [PMID: 39660369 DOI: 10.1111/iej.14180] [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: 04/29/2024] [Revised: 10/26/2024] [Accepted: 11/22/2024] [Indexed: 12/12/2024]
Abstract
BACKGROUND Dental pulp tissue engineering is expected to become an ideal treatment for irreversible pulpitis and apical periodontitis. However, angiogenesis and neurogenesis for functional pulp regeneration have not yet met the standard for large-scale clinical application, and need further research. OBJECTIVE This review focused on the potential mechanisms of angiogenesis and neurogenesis in pulp regeneration, including stem cell types, upstream and downstream regulatory molecules and cascade signalling pathways, thereby providing a theoretical basis and inspiring new ideas to improve the effectiveness of dental pulp tissue engineering. METHODS An electronic literature search was carried out using the keywords of 'pulp regeneration', 'stem cell transplantation', 'dental pulp stem cells', 'angiogenesis' and 'neurogenesis'. The resulting literature was screened and reviewed. RESULTS Stem cells used in dental pulp tissue engineering can be classified as dental-derived and non-dental-derived stem cells, amongst which dental pulp stem cells (DPSC) have achieved promising results in animal experiments and clinical trials. Multiple molecules and signalling pathways are involved in the process of DPSC-mediated angiogenic and neurogenetic regeneration. In order to promote angiogenesis and neurogenesis in pulp regeneration, feasible measures include the addition of growth factors, the modulation of transcription factors and signalling pathways, the use of extracellular vesicles and the modification of bioscaffold materials. CONCLUSION Dental pulp tissue engineering has had breakthroughs in preclinical and clinical studies in vivo. Overcoming difficulties in pulpal angiogenesis and neurogenesis, and achieving functional pulp regeneration will lead to a significant impact in endodontics.
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Affiliation(s)
- Wanting Su
- School of Stomatology, Jinan University, Guangzhou, China
| | - Chufang Liao
- School of Stomatology, Jinan University, Guangzhou, China
- Clinical Research Platform for Interdiscipline of Stomatology, Jinan University, Guangzhou, China
- Hospital of stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Xiangning Liu
- School of Stomatology, Jinan University, Guangzhou, China
- Clinical Research Platform for Interdiscipline of Stomatology, Jinan University, Guangzhou, China
- Hospital of stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, China
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4
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Fischer NG, de Souza Araújo IJ, Daghrery A, Yu B, Dal-Fabbro R, Dos Reis-Prado AH, Silikas N, Rosa V, Aparicio C, Watts DC, Bottino MC. Guidance on biomaterials for periodontal tissue regeneration: Fabrication methods, materials and biological considerations. Dent Mater 2025; 41:283-305. [PMID: 39794220 DOI: 10.1016/j.dental.2024.12.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025]
Abstract
Regeneration of the multiple tissues and interfaces in the periodontal complex necessitates multidisciplinary evaluation to establish structure/function relationships. This article, an initiative of the Academy of Dental Materials, provides guidance for performing chemical, structural, and mechanical characterization of materials for periodontal tissue regeneration, and outlines important recommendations on methods of testing bioactivity, biocompatibility, and antimicrobial properties of biomaterials/scaffolds for periodontal tissue engineering. First, we briefly summarize periodontal tissue engineering fabrication methods. We then highlight critical variables to consider when evaluating a material for periodontal tissue regeneration, and the fundamental tests used to investigate them. The recommended tests and designs incorporate relevant international standards and provide a framework for characterizing newly developed materials focusing on the applicability of those tests for periodontal tissue regeneration. The most common methods of biofabrication (electrospinning, injectable hydrogels, fused deposition modelling, melt electrowriting, and bioprinting) and their specific applications in periodontal tissue engineering are reviewed. The critical techniques for morphological, chemical, and mechanical characterization of different classes of materials used in periodontal regeneration are then described. The major advantages and drawbacks of each assay, sample sizes, and guidelines on specimen preparation are also highlighted. From a biological standpoint, fundamental methods for testing bioactivity, the biocompatibility of materials, and the experimental models for testing the antimicrobial potential are included in this guidance. In conclusion, researchers performing studies on periodontal tissue regeneration will have this guidance as a tool to assess essential properties and characteristics of their materials/scaffold-based strategies.
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Affiliation(s)
- Nicholas G Fischer
- Minnesota Dental Research Center for Biomaterials and Biomechanics, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA
| | - Isaac J de Souza Araújo
- Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA
| | - Arwa Daghrery
- Department of Restorative Dental Sciences, School of Dentistry, Jazan University, Jazan 82943, KSA; Department of Cariology, Restorative Sciences and Endodontics, University of Michigan, School of Dentistry, Ann Arbor, MI 48109, USA
| | - Baiqing Yu
- Faculty of Dentistry, National University of Singapore, Singapore
| | - Renan Dal-Fabbro
- Department of Cariology, Restorative Sciences and Endodontics, University of Michigan, School of Dentistry, Ann Arbor, MI 48109, USA
| | - Alexandre H Dos Reis-Prado
- Department of Cariology, Restorative Sciences and Endodontics, University of Michigan, School of Dentistry, Ann Arbor, MI 48109, USA; Department of Restorative Dentistry, School of Dentistry, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil
| | - Nikolaos Silikas
- Dental Biomaterials, Dentistry, The University of Manchester, Manchester, United Kingdom
| | - Vinicius Rosa
- Faculty of Dentistry, National University of Singapore, Singapore; ORCHIDS: Oral Care Health Innovations and Designs Singapore, National University of Singapore, Singapore
| | - Conrado Aparicio
- BOBI-Bioinspired Oral Biomaterials and Interfaces, UPC-Universitat Politènica de Catalunya, Barcelona 08010, Spain; Catalan Institute for Research and Advanced Studies (ICREA), Barcelona 08010, Spain; SCOI - Study and Control of Oral Infections, Faculty of Odontology, UIC Barcelona-Universitat Internacional de Catalunya, Sant Cugat del Vallès, Spain; IBEC - Institute for Bioengineering of Catalonia, Barcelona, Spain
| | - David C Watts
- School of Medical Sciences and Photon Science Institute, University of Manchester, United Kingdom
| | - Marco C Bottino
- Department of Cariology, Restorative Sciences and Endodontics, University of Michigan, School of Dentistry, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
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Rosa V, Cavalcanti BN, Nör JE, Tezvergil-Mutluay A, Silikas N, Bottino MC, Kishen A, Soares DG, Franca CM, Cooper PR, Duncan HF, Ferracane JL, Watts DC. Guidance for evaluating biomaterials' properties and biological potential for dental pulp tissue engineering and regeneration research. Dent Mater 2025; 41:248-264. [PMID: 39674710 PMCID: PMC11875114 DOI: 10.1016/j.dental.2024.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 12/10/2024] [Indexed: 12/16/2024]
Abstract
BACKGROUND Dental pulp regeneration is a complex and advancing field that requires biomaterials capable of supporting the pulp's diverse functions, including immune defense, sensory perception, vascularization, and reparative dentinogenesis. Regeneration involves orchestrating the formation of soft connective tissues, neurons, blood vessels, and mineralized structures, necessitating materials with tailored biological and mechanical properties. Numerous biomaterials have entered clinical practice, while others are being developed for tissue engineering applications. The composition and a broad range of material properties, such as surface characteristics, degradation rate, and mechanical strength, significantly influence cellular behavior and tissue outcomes. This underscores the importance of employing robust evaluation methods and ensuring precise and comprehensive reporting of findings to advance research and clinical translation. AIMS This article aims to present the biological foundations of dental pulp tissue engineering alongside potential testing methodologies and their advantages and limitations. It provides guidance for developing research protocols to evaluate the properties of biomaterials and their influences on cell and tissue behavior, supporting progress toward effective dental pulp regeneration strategies.
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Affiliation(s)
- Vinicius Rosa
- Faculty of Dentistry, National University of Singapore, Singapore; ORCHIDS: Oral Care Health Innovations and Designs Singapore, National University of Singapore, Singapore.
| | - Bruno Neves Cavalcanti
- Department of Cariology, Restorative Sciences, and Endodontics, Division of Endodontics, School of Dentistry, University of Michigan, Ann Arbor, United States.
| | - Jacques E Nör
- Department of Cariology, Restorative Sciences, and Endodontics, Division of Endodontics, School of Dentistry, University of Michigan, Ann Arbor, United States.
| | - Arzu Tezvergil-Mutluay
- Department of Cariology and Restorative Dentistry, Institute of Dentistry, University of Turku, Turku, Finland; Turku University Hospital, TYKS, Turku, Finland.
| | - Nikolaos Silikas
- Division of Dentistry, School of Medical Sciences, University of Manchester, Manchester, United Kingdom.
| | - Marco C Bottino
- Department of Cariology, Restorative Sciences, and Endodontics, Division of Endodontics, School of Dentistry, University of Michigan, Ann Arbor, United States; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, United States.
| | - Anil Kishen
- Faculty of Dentistry, University of Toronto, Toronto, Canada; Department of Dentistry, Mount Sinai Health System, Mount Sinai Hospital, Toronto, Canada.
| | - Diana Gabriela Soares
- Department of Operative Dentistry, Endodontics and Dental Materials, School of Dentistry, São Paulo University, Bauru, Brazil.
| | - Cristiane M Franca
- Department of Oral Rehabilitation and Biosciences, School of Dentistry, Oregon Health & Science University (OHSU), Portland, USA; Knight Cancer Precision Biofabrication Hub, Oregon Health & Science University (OHSU), Portland, USA.
| | - Paul Roy Cooper
- Sir John Walsh Research Institute, Department of Oral Sciences, Faculty of Dentistry, University of Otago, New Zealand.
| | - Henry F Duncan
- Division of Restorative Dentistry and Periodontology, Dublin Dental University Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland.
| | - Jack L Ferracane
- Department of Oral Rehabilitation and Biosciences, School of Dentistry, Oregon Health & Science University (OHSU), Portland, USA.
| | - David C Watts
- Division of Dentistry, School of Medical Sciences, University of Manchester, Manchester, United Kingdom.
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Kim Y, Park HJ, Kim MK, Kim HJ, Kim YI, Bae SK, Bae MK. Effects of Hispidulin on the Osteo/Odontogenic and Endothelial Differentiation of Dental Pulp Stem Cells. Pharmaceuticals (Basel) 2024; 17:1740. [PMID: 39770583 PMCID: PMC11678453 DOI: 10.3390/ph17121740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Revised: 12/20/2024] [Accepted: 12/21/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Human dental pulp stem cells (HDPSCs) with multi-lineage differentiation potential and migration ability are required for HDPSC-based bone and dental regeneration. Hispidulin is a naturally occurring flavonoid with diverse pharmacological activities, but its effects on biological properties of HDPSCs remain unknown. Therefore, we investigated the effects of hispidulin on the differentiation potential and migration ability of HDPSCs and elucidated their underlying mechanisms. Methods: The osteo/odontogenic capacity of HDPSCs was assessed using the alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. The migration ability of HDPSCs was evaluated using a scratch wound assay. Furthermore, the endothelial differentiation of HDPSCs was examined by using a capillary sprouting assay and by assessing CD31 expression. Results: Hispidulin significantly enhanced the osteo/odontogenic differentiation of HDPSCs with increased expression of osteo/odontogenic differentiation markers. Hispidulin increased the migration of HDPSCs, which was mediated by the upregulation of C-X-C chemokine receptor type 4 (CXCR4). The treatment of HDPSCs with hispidulin enhanced the differentiation of HDPSCs into endothelial cells, as evidenced by increased capillary sprouting and endothelial marker expression. In addition, we demonstrated that hispidulin activated the ERK1/2 signaling, and its inhibition by U0126 significantly suppressed the hispidulin-induced endothelial differentiation of HDPSCs. Conclusions: These findings demonstrate that hispidulin effectively promotes the osteo/odontogenic and endothelial differentiation, and migration of HDPSCs. These results suggest that hispidulin may have potential therapeutic applications in dental pulp regeneration and tissue engineering.
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Affiliation(s)
- Yeon Kim
- Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea (H.J.K.)
- Periodontal Disease Signaling Network Research Center (MRC), School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea;
- Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea
| | - Hyun-Joo Park
- Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea (H.J.K.)
- Periodontal Disease Signaling Network Research Center (MRC), School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea;
- Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea
| | - Mi-Kyoung Kim
- Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea (H.J.K.)
- Periodontal Disease Signaling Network Research Center (MRC), School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea;
| | - Hyung Joon Kim
- Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea (H.J.K.)
- Periodontal Disease Signaling Network Research Center (MRC), School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea;
- Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea
| | - Yong-Il Kim
- Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea
- Department of Orthodontics, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea
| | - Soo-Kyung Bae
- Periodontal Disease Signaling Network Research Center (MRC), School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea;
- Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea
- Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea
| | - Moon-Kyoung Bae
- Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea (H.J.K.)
- Periodontal Disease Signaling Network Research Center (MRC), School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea;
- Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea
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7
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Chatzopoulou E, Bousaidi N, Guilbert T, Rucher G, Rose J, Germain S, Rouzet F, Chaussain C, Muller L, Gorin C. Multiscale Imaging to Monitor Functional SHED-Supported Engineered Vessels. J Dent Res 2024; 103:1392-1402. [PMID: 39290146 DOI: 10.1177/00220345241271122] [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] [Indexed: 09/19/2024] Open
Abstract
Regeneration of orofacial tissues is hampered by the lack of adequate vascular supply. Implantation of in vitro engineered, prevascularized constructs has emerged as a strategy to allow the rapid vascularization of the entire graft. Given the angiogenic properties of dental pulp stem cells, we hereby established a preclinical model of prevascularized constructs loaded with stem cells from human exfoliating deciduous teeth (SHED) in a 3-dimensional-printed material and provided a functional analysis of their in vivo angiogenesis, vascular perfusion, and permeability. Three different cell-loaded collagen hydrogels (SHED-human umbilical vein endothelial cell [HUVEC], HUVEC with SHED-conditioned medium, and SHED alone) were cast in polylactic acid (PLA) grids and ectopically implanted in athymic mice. At day 10, in vivo positron emission tomography (PETscan) revealed a significantly increased uptake of radiotracer targeting activated endothelial cells in the SHED-HUVEC group compared to the other groups. At day 30, ex vivo micro-computed tomography imaging confirmed that SHED-HUVEC constructs had a significantly increased vascular volume compared to the other ones. Injection of species-specific lectins analyzed by 2-photon microscopy demonstrated blood perfusion of the engineered human vessels in both prevascularized groups. However, in vivo quantification showed increased vessel density in the SHED-HUVEC group. In addition, coinjection of fluorescent lectin and dextran revealed that prevascularization with SHED prevented vascular leakage, demonstrating the active role of SHED in the maturation of human-engineered microvascular networks. This preclinical study introduces a novel PLA prevascularized and implantable construct, along with an array of imaging techniques, to validate the ability of SHED to promote functional human-engineered vessels, further highlighting the interest of SHED for orofacial tissue engineering. Furthermore, this study validates the use of PETscan for the early detection of in vivo angiogenesis, which may be applied in the clinic to monitor the performance of prevascularized grafts.
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Affiliation(s)
- E Chatzopoulou
- Université Paris Cité, URP2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant, Montrouge, France
- AP-HP, Services de médecine bucco-dentaire, FHU DDS-Net, GH Paris Nord et Paris Est, France
| | - N Bousaidi
- Université Paris Cité, URP2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant, Montrouge, France
| | - T Guilbert
- Université Paris Cité, CNRS, INSERM U1016, Institut Cochin, Paris, France
| | - G Rucher
- Université Paris Cité, LVTS, INSERM U1148, France
- Université Paris Cité, UMS 34-FRIM, France
| | - J Rose
- AP-HP, Département de médecine nucléaire, Hôpital Bichat, Paris, France
| | - S Germain
- Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS UMR7241, INSERM U1050, Université PSL, Paris, France
| | - F Rouzet
- Université Paris Cité, LVTS, INSERM U1148, France
- AP-HP, Département de médecine nucléaire, Hôpital Bichat, Paris, France
| | - C Chaussain
- Université Paris Cité, URP2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant, Montrouge, France
- AP-HP, Services de médecine bucco-dentaire, FHU DDS-Net, GH Paris Nord et Paris Est, France
| | - L Muller
- Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS UMR7241, INSERM U1050, Université PSL, Paris, France
| | - C Gorin
- Université Paris Cité, URP2496 Pathologies, Imagerie et Biothérapies Orofaciales et Plateforme Imagerie du Vivant, Montrouge, France
- AP-HP, Services de médecine bucco-dentaire, FHU DDS-Net, GH Paris Nord et Paris Est, France
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8
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Han Z, Lin Y, Guo X, Xu J, Gao X, Yang R, Zhao Y, Gui M, Zhang L, Guo Y, Chen Z. "Osteo-Organogenesis Niche" Hyaluronic Acid Engineered Materials Directing Re-Osteo-Organogenesis via Manipulating Macrophage CD44-MAPK/ERK-ETV1/5-MRC1 Axis. Adv Healthc Mater 2024; 13:e2403122. [PMID: 39440638 DOI: 10.1002/adhm.202403122] [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: 08/20/2024] [Revised: 10/06/2024] [Indexed: 10/25/2024]
Abstract
The strategy of re-organogenesis provides an optimal framework for restoring complex organ structures and functions in adult damage. While the focus has often been on restoring organogenesis stem cells, there is limited investigations of reverting the environmental niche to support this approach. The guiding principle of "Nature selects the fittest to survive" drives the intricate dynamic changes in cellular events within the niche environment, especially through immune surveillance. The extracellular matrix (ECM) serves as the "self-associated molecular patterns" of the niche, containing extensive data on cell-niche reaction data and acting as the active tuner of immune surveillance. In this study, hyaluronic acid (HA) is identified as a unique component of the ECM in cranial osteo-organogenesis. Mechanistically, HA activates the Cluster of Differentiation 44 (CD44)-Mitogen-Activated Protein Kinase (MAPK)/Extracellular Signal-Regulated Kinase (ERK)-Ets Variant 1/5 (ETV1/5)- Mannose Receptor C-Type 1 (MRC1) axis in macrophages, establishing a distinct immune surveillance during osteo-organogenesis. Furthermore, HA is utilized as a novel engineered material for an "Osteo-organogenesis niche", restoring immune surveillance and synergistically regulating stem cells to achieve re-osteo-organogenesis in cranial defects of rats. Taken together, the study unveils a previously unknown strategy for leveraging re-organogenesis by utilizing "organogenesis niche" ECM engineered materials to manipulate immune surveillance, thereby comprehensively regulating stem cells and other tissue cells effectively for re-organogenesis.
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Affiliation(s)
- Zongpu Han
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
- Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, China
| | - Yixiong Lin
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
- Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, China
| | - Xinyu Guo
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
- Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, China
| | - Jieyun Xu
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
- Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, China
| | - Xiaomeng Gao
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
- Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, China
| | - Ruihan Yang
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
- Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, China
| | - Yuan Zhao
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
- Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, China
| | - Mixiao Gui
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
- Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, China
| | - Linjun Zhang
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
- Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, China
| | - Yuanlong Guo
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
- Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, China
| | - Zetao Chen
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
- Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou, 510055, China
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9
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Dobrzyńska‐Mizera M, Dodda JM, Liu X, Knitter M, Oosterbeek RN, Salinas P, Pozo E, Ferreira AM, Sadiku ER. Engineering of Bioresorbable Polymers for Tissue Engineering and Drug Delivery Applications. Adv Healthc Mater 2024; 13:e2401674. [PMID: 39233521 PMCID: PMC11616265 DOI: 10.1002/adhm.202401674] [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: 05/06/2024] [Revised: 08/15/2024] [Indexed: 09/06/2024]
Abstract
Herein, the recent advances in the development of resorbable polymeric-based biomaterials, their geometrical forms, resorption mechanisms, and their capabilities in various biomedical applications are critically reviewed. A comprehensive discussion of the engineering approaches for the fabrication of polymeric resorbable scaffolds for tissue engineering, drug delivery, surgical, cardiological, aesthetical, dental and cardiovascular applications, are also explained. Furthermore, to understand the internal structures of resorbable scaffolds, representative studies of their evaluation by medical imaging techniques, e.g., cardiac computer tomography, are succinctly highlighted. This approach provides crucial clinical insights which help to improve the materials' suitable and viable characteristics for them to meet the highly restrictive medical requirements. Finally, the aspects of the legal regulations and the associated challenges in translating research into desirable clinical and marketable materials of polymeric-based formulations, are presented.
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Affiliation(s)
| | - Jagan Mohan Dodda
- New Technologies – Research Centre (NTC)University of West BohemiaUniverzitní 8Pilsen30100Czech Republic
| | - Xiaohua Liu
- Chemical and Biomedical Engineering DepartmentUniversity of Missouri1030 Hill StreetColumbiaMissouri65211USA
| | - Monika Knitter
- Institute of Materials TechnologyPolymer DivisionPoznan University of TechnologyPoznanPoland
| | - Reece N. Oosterbeek
- Department of Engineering ScienceUniversity of OxfordParks RoadOxfordOX1 3PJUK
| | - Pablo Salinas
- Department of CardiologyHospital Clínico San CarlosMadridSpain
- Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)MadridSpain
| | - Eduardo Pozo
- Department of CardiologyHospital Clínico San CarlosMadridSpain
- Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)MadridSpain
| | - Ana Marina Ferreira
- School of EngineeringNewcastle UniversityNewcastle upon TyneNewcastleNE1 7RUUK
| | - Emmanuel Rotimi Sadiku
- Tshwane University of TechnologyDepartment of ChemicalMetallurgical and Materials EngineeringPolymer Division & Institute for Nano Engineering Research (INER)Pretoria West CampusPretoriaSouth Africa
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10
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Fatima Balderrama I, Schafer S, El Shatanofy M, Bergamo ETP, Mirsky NA, Nayak VV, Marcantonio Junior E, Alifarag AM, Coelho PG, Witek L. Biomimetic Tissue Engineering Strategies for Craniofacial Applications. Biomimetics (Basel) 2024; 9:636. [PMID: 39451842 PMCID: PMC11506466 DOI: 10.3390/biomimetics9100636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 09/21/2024] [Accepted: 10/11/2024] [Indexed: 10/26/2024] Open
Abstract
Biomimetics is the science of imitating nature's designs and processes to create innovative solutions for various fields, including dentistry and craniofacial reconstruction. In these areas, biomimetics involves drawing inspiration from living organisms/systems to develop new materials, techniques, and devices that closely resemble natural tissue structures and enhance functionality. This field has successfully demonstrated its potential to revolutionize craniofacial procedures, significantly improving patient outcomes. In dentistry, biomimetics offers exciting possibilities for the advancement of new dental materials, restorative techniques, and regenerative potential. By analyzing the structure/composition of natural teeth and the surrounding tissues, researchers have developed restorative materials that mimic the properties of teeth, as well as regenerative techniques that might assist in repairing enamel, dentin, pulp, cementum, periodontal ligament, and bone. In craniofacial reconstruction, biomimetics plays a vital role in developing innovative solutions for facial trauma, congenital defects, and various conditions affecting the maxillofacial region. By studying the intricate composition and mechanical properties of the skull and facial bones, clinicians and engineers have been able to replicate natural structures leveraging computer-aided design and manufacturing (CAD/CAM) and 3D printing. This has allowed for the creation of patient-specific scaffolds, implants, and prostheses that accurately fit a patient's anatomy. This review highlights the current evidence on the application of biomimetics in the fields of dentistry and craniofacial reconstruction.
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Affiliation(s)
- Isis Fatima Balderrama
- Department of Diagnosis and Surgery, School of Dentistry of Araraquara, Sao Paulo State University, Sao Paulo 14801-385, Brazil
- Biomaterials Division, NYU Dentistry, New York, NY 10010, USA
| | - Sogand Schafer
- Division of Plastic, Reconstructive and Oral Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
| | - Muhammad El Shatanofy
- Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Edmara T. P. Bergamo
- Biomaterials Division, NYU Dentistry, New York, NY 10010, USA
- Department of Prosthodontics, NYU Dentistry, New York, NY 10010, USA
| | | | - Vasudev Vivekanand Nayak
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Elcio Marcantonio Junior
- Department of Diagnosis and Surgery, School of Dentistry of Araraquara, Sao Paulo State University, Sao Paulo 14801-385, Brazil
| | - Adham M. Alifarag
- Department of General Surgery, Temple University Hospital System, Philadelphia, PA 19140, USA
| | - Paulo G. Coelho
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Division of Plastic Surgery, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Lukasz Witek
- Biomaterials Division, NYU Dentistry, New York, NY 10010, USA
- Department of Biomedical Engineering, NYU Tandon School of Engineering, Brooklyn, NY 11201, USA
- Hansjörg Wyss Department of Plastic Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA
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11
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Quigley RM, Kearney M, Kennedy OD, Duncan HF. Tissue engineering approaches for dental pulp regeneration: The development of novel bioactive materials using pharmacological epigenetic inhibitors. Bioact Mater 2024; 40:182-211. [PMID: 38966600 PMCID: PMC11223092 DOI: 10.1016/j.bioactmat.2024.06.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 06/05/2024] [Accepted: 06/06/2024] [Indexed: 07/06/2024] Open
Abstract
The drive for minimally invasive endodontic treatment strategies has shifted focus from technically complex and destructive root canal treatments towards more conservative vital pulp treatment. However, novel approaches to maintaining dental pulp vitality after disease or trauma will require the development of innovative, biologically-driven regenerative medicine strategies. For example, cell-homing and cell-based therapies have recently been developed in vitro and trialled in preclinical models to study dental pulp regeneration. These approaches utilise natural and synthetic scaffolds that can deliver a range of bioactive pharmacological epigenetic modulators (HDACis, DNMTis, and ncRNAs), which are cost-effective and easily applied to stimulate pulp tissue regrowth. Unfortunately, many biological factors hinder the clinical development of regenerative therapies, including a lack of blood supply and poor infection control in the necrotic root canal system. Additional challenges include a need for clinically relevant models and manufacturing challenges such as scalability, cost concerns, and regulatory issues. This review will describe the current state of bioactive-biomaterial/scaffold-based engineering strategies to stimulate dentine-pulp regeneration, explicitly focusing on epigenetic modulators and therapeutic pharmacological inhibition. It will highlight the components of dental pulp regenerative approaches, describe their current limitations, and offer suggestions for the effective translation of novel epigenetic-laden bioactive materials for innovative therapeutics.
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Affiliation(s)
- Ross M. Quigley
- Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin (TCD), University of Dublin, Lincoln Place, Dublin, Ireland
- Department of Anatomy and Regenerative Medicine, and Tissue Engineering Research Group, Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin, Ireland
| | - Michaela Kearney
- Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin (TCD), University of Dublin, Lincoln Place, Dublin, Ireland
| | - Oran D. Kennedy
- Department of Anatomy and Regenerative Medicine, and Tissue Engineering Research Group, Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin, Ireland
- The Trinity Centre for Biomedical Engineering (TCBE) and the Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland (RCSI) and Trinity College Dublin (TCD), Dublin, Ireland
| | - Henry F. Duncan
- Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin (TCD), University of Dublin, Lincoln Place, Dublin, Ireland
- The Trinity Centre for Biomedical Engineering (TCBE) and the Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland (RCSI) and Trinity College Dublin (TCD), Dublin, Ireland
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12
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Aytekin A, Yazir Y, Duruksu G, Öztürk A. Comparison of aquaporin profile of advanced passage mesenchymal stem cells with early passage mesenchymal stem cells and determination of its effect on adipogenic differentiation efficiency. Tissue Cell 2024; 89:102448. [PMID: 38917601 DOI: 10.1016/j.tice.2024.102448] [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: 05/02/2024] [Revised: 06/11/2024] [Accepted: 06/14/2024] [Indexed: 06/27/2024]
Abstract
OBJECTIVE Our study aimed to compare aquaporin profiles in advanced and early passage bone marrow-derived mesenchymal stem cells (BM-MSCs) and assess the impact of aquaporin changes after adipogenic differentiation. Aquaporins are crucial for stem cell survival and differentiation during their life cycle. We focused on the role of aquaporins in the cell structures of advanced and early passage stem cells. METHODS In our study, BM-MSCs were used for our objectives. Characterization of the cells was evaluated via flow cytometry using stem cell surface markers. The characterized BM-MSCs were divided into control and differentiation groups at passages 3 (P3) and 8 (P8). AQP1, AQP3, AQP7, AQP9, and AQP10 expression levels on days 0, 1, 3, 7, 14, and 21 were evaluated using Real Time-PCR, ELISA, and immunofluorescence studies. RESULTS The cells were characterized by flow cytometry and confirmed to exhibit BM-MSC characteristics. At P3 and P8, differentiation was initiated, and AQP protein expression was observed to initially increase and then decrease on subsequent days. The increase in AQP protein expression at P3 occurred earlier than that at P8. Gene expression analysis demonstrated a statistically significant increase in AQP gene expression on days when AQP protein expression decreased. Moreover, statistical differences were observed between late and early passage AQP profiles. CONCLUSION Our study examined the composition of AQPs in BM-MSCs in association with cell passage, and found that AQPs play a role in the differentiation process. The connection between the AQP profile and aging might be related to differentiation capacity, which could have implications for slowing down cellular aging and developing new therapeutic approaches.
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Affiliation(s)
- Ayşegül Aytekin
- Department of Histology and Embryology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
| | - Yusufhan Yazir
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey; Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University, Kocaeli, Turkey; Department of Histology and Embryology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey.
| | - Gökhan Duruksu
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey; Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University, Kocaeli, Turkey
| | - Ahmet Öztürk
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey; Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University, Kocaeli, Turkey; Department of Histology and Embryology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
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13
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Zhang H, Li L, Sun X, Hou B, Luo C. Research and development of microenvironment's influence on stem cells from the apical papilla - construction of novel research microdevices: tooth-on-a-chip. Biomed Microdevices 2024; 26:33. [PMID: 39023652 DOI: 10.1007/s10544-024-00715-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/29/2024] [Indexed: 07/20/2024]
Abstract
Stem cells are crucial in tissue engineering, and their microenvironment greatly influences their behavior. Among the various dental stem cell types, stem cells from the apical papilla (SCAPs) have shown great potential for regenerating the pulp-dentin complex. Microenvironmental cues that affect SCAPs include physical and biochemical factors. To research optimal pulp-dentin complex regeneration, researchers have developed several models of controlled biomimetic microenvironments, ranging from in vivo animal models to in vitro models, including two-dimensional cultures and three-dimensional devices. Among these models, the most powerful tool is a microfluidic microdevice, a tooth-on-a-chip with high spatial resolution of microstructures and precise microenvironment control. In this review, we start with the SCAP microenvironment in the regeneration of pulp-dentin complexes and discuss research models and studies related to the biological process.
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Affiliation(s)
- Hexuan Zhang
- Center for Microscope Enhanced Dentistry, School of Stomatology, Capital Medical University, Beijing, China
- Department of Endodontics and Operative Dentistry, School of Stomatology, Capital Medical University, Beijing, China
| | - Lingjun Li
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China
| | - Xiaoqiang Sun
- Department of Endodontics and Operative Dentistry, School of Stomatology, Capital Medical University, Beijing, China.
| | - Benxiang Hou
- Center for Microscope Enhanced Dentistry, School of Stomatology, Capital Medical University, Beijing, China.
| | - Chunxiong Luo
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China.
- The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, China.
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14
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Santilli F, Fabrizi J, Santacroce C, Caissutti D, Spinello Z, Candelise N, Lancia L, Pulcini F, Delle Monache S, Mattei V. Analogies and Differences Between Dental Stem Cells: Focus on Secretome in Combination with Scaffolds in Neurological Disorders. Stem Cell Rev Rep 2024; 20:159-174. [PMID: 37962698 PMCID: PMC10799818 DOI: 10.1007/s12015-023-10652-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/02/2023] [Indexed: 11/15/2023]
Abstract
Mesenchymal stem cells (MSCs) are well known for their beneficial effects, differentiation capacity and regenerative potential. Dental-derived MSCs (DSCs) are more easily accessible and have a non-invasive isolation method rather than MSCs isolated from other sources (umbilical cord, bone marrow, and adipose tissue). In addition, DSCs appear to have a relevant neuro-regenerative potential due to their neural crest origin. However, it is now known that the beneficial effects of MSCs depend, at least in part, on their secretome, referring to all the bioactive molecules (neurotrophic factors) released in the conditioned medium (CM) or in the extracellular vesicles (EVs) in particular exosomes (Exos). In this review, we described the similarities and differences between various DSCs. Our focus was on the secretome of DSCs and their applications in cell therapy for neurological disorders. For neuro-regenerative purposes, the secretome of different DSCs has been tested. Among these, the secretome of dental pulp stem cells and stem cells from human exfoliated deciduous teeth have been the most widely studied. Both CM and Exos obtained from DSCs have been shown to promote neurite outgrowth and neuroprotective effects as well as their combination with scaffold materials (to improve their functional integration in the tissue). For these reasons, the secretome obtained from DSCs in combination with scaffold materials may represent a promising tissue engineering approach for neuroprotective and neuro-regenerative treatments.
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Affiliation(s)
- Francesca Santilli
- Biomedicine and Advanced Technologies Rieti Center, "Sabina Universitas", Via A.M. Ricci 35/A, 02100, Rieti, Italy
| | - Jessica Fabrizi
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Costantino Santacroce
- Biomedicine and Advanced Technologies Rieti Center, "Sabina Universitas", Via A.M. Ricci 35/A, 02100, Rieti, Italy
| | - Daniela Caissutti
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Zaira Spinello
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Niccolò Candelise
- National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 29900161, Rome, Italy
| | - Loreto Lancia
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy
| | - Fanny Pulcini
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy
| | - Simona Delle Monache
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy.
| | - Vincenzo Mattei
- Dipartimento di Scienze della Vita, della Salute e delle Professioni Sanitarie, Link Campus University, Via del Casale di San Pio V 44, 00165, Rome, Italy.
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15
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Mantesso A, Nör JE. Stem cells in clinical dentistry. J Am Dent Assoc 2023; 154:1048-1057. [PMID: 37804275 PMCID: PMC11827052 DOI: 10.1016/j.adaj.2023.08.007] [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: 05/15/2023] [Revised: 08/11/2023] [Accepted: 08/22/2023] [Indexed: 10/09/2023]
Abstract
BACKGROUND Stem cells are present in most of the tissues in the craniofacial complex and play a major role in tissue homeostasis and repair. These cells are characterized by their capacity to differentiate into multiple cell types and to self-renew to maintain a stem cell pool throughout the life of the tissue. TYPES OF STUDIES REVIEWED The authors discuss original data from experiments and comparative analyses and review articles describing the identification and characterization of stem cells of the oral cavity. RESULTS Every oral tissue except enamel, dentin, and cementum contains stem cells for the entire life span. These stem cells self-renew to maintain a pool of cells that can be activated to replace terminally differentiated cells (for example, odontoblasts) or to enable wound healing (for example, dentin bridge in pulp exposures and healing of periodontal tissues after surgery). In addition, dental stem cells can differentiate into functional blood vessels and nerves. Initial clinical trials have shown that transplanting dental pulp stem cells into disinfected necrotic teeth has allowed for the recovery of tooth vitality and vertical and horizontal root growth in immature teeth with incomplete root formation. PRACTICAL IMPLICATIONS As a consequence of these groundbreaking discoveries, stem cell banks are now offering services for the cryopreservation of dental stem cells. The future use of stem cell-based therapies in the clinic will depend on the collaboration of clinicians and researchers in projects designed to understand whether these treatments are safe, efficacious, and clinically feasible.
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Affiliation(s)
- Andrea Mantesso
- Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - Jacques E. Nör
- Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA
- Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, USA
- Department of Otolaryngology, University of Michigan School of Medicine
- Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Ann Arbor, Michigan, 48109, USA
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16
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Yadav P, Vats R, Bano A, Namdev R, Bhardwaj R. Ameliorative potential of stem cells from human exfoliated deciduous teeth (SHED) in preclinical studies: A meta-analysis. Regen Ther 2023; 24:117-134. [PMID: 37441223 PMCID: PMC10333108 DOI: 10.1016/j.reth.2023.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 05/27/2023] [Accepted: 06/07/2023] [Indexed: 07/15/2023] Open
Abstract
The preclinical and clinical role of mesenchymal stem cells from various adult sources is extensively investigated and established in regenerative medicine. However, the comprehensive exploration of the therapeutic potential of Stem cells from human exfoliated deciduous teeth (SHED) is inadequate. Therefore, we performed a systematic meta-analysis of preclinical animal model studies in several diseases to provide insight into SHED's efficacy and therapeutic potential. Two blinded and independent investigators searched the available online databases and scrutinized the included studies. Meta-analysis was performed to evaluate the pooled effect estimate of intervention of SHED by Review Manager 5.4.1. To investigate the therapeutic efficacy of SHED intervention, we also analyzed the test of heterogeneity (I2), overall effect (Z), sensitivity, and publication bias. Among the 2156 scrutinized studies, 40 were included and evaluated as per inclusion and exclusion criteria. The intervention of SHED and its derivatives in several diseases depicted statistically significant therapeutic effects in periodontitis, pulpitis, spinal cord injury, parkinson's disease, alzheimer's disease, focal cerebral ischemia, peripheral nerve injury, and retinal pigmentosa. SHED also improved levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin in liver fibrosis . In autoimmune diseases also, values were significant. SHED also showed a statistically significant reduction of wound healing area and new bone formation in bone defects. The pooled effect estimates of included preclinical studies demonstrated a statistically significant therapeutic effect of SHED in numerous diseases. Based on our data, it is suggested that the potential of SHED may be implemented in clinical trials after conducting a few more preclinical studies.
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Affiliation(s)
- Pooja Yadav
- Stem Cell Biology Laboratory, Centre for Medical Biotechnology, Maharshi Dayanand University Rohtak, 124001, India
| | - Ravina Vats
- Stem Cell Biology Laboratory, Centre for Medical Biotechnology, Maharshi Dayanand University Rohtak, 124001, India
| | - Afsareen Bano
- Stem Cell Biology Laboratory, Centre for Medical Biotechnology, Maharshi Dayanand University Rohtak, 124001, India
| | - Ritu Namdev
- Dept. of Pediatric Dentistry, Post Graduate Institute of Dental Sciences, Rohtak, 124001, India
| | - Rashmi Bhardwaj
- Stem Cell Biology Laboratory, Centre for Medical Biotechnology, Maharshi Dayanand University Rohtak, 124001, India
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17
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Ren K, Vickers R, Murillo J, Ruparel NB. Revolutionizing orofacial pain management: the promising potential of stem cell therapy. FRONTIERS IN PAIN RESEARCH 2023; 4:1239633. [PMID: 38028430 PMCID: PMC10679438 DOI: 10.3389/fpain.2023.1239633] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 09/22/2023] [Indexed: 12/01/2023] Open
Abstract
Orofacial pain remains a significant health issue in the United States. Pain originating from the orofacial region can be composed of a complex array of unique target tissue that contributes to the varying success of pain management. Long-term use of analgesic drugs includes adverse effects such as physical dependence, gastrointestinal bleeding, and incomplete efficacy. The use of mesenchymal stem cells for their pain relieving properties has garnered increased attention. In addition to the preclinical and clinical results showing stem cell analgesia in non-orofacial pain, studies have also shown promising results for orofacial pain treatment. Here we discuss the outcomes of mesenchymal stem cell treatment for pain and compare the properties of stem cells from different tissues of origin. We also discuss the mechanism underlying these analgesic/anti-nociceptive properties, including the role of immune cells and the endogenous opioid system. Lastly, advancements in the methods and procedures to treat patients experiencing orofacial pain with mesenchymal stem cells are also discussed.
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Affiliation(s)
- Ke Ren
- Department of Pain and Neural Sciences, University of Maryland, Baltimore, MD, United States
| | - Russel Vickers
- Clinical Stem Cells Pty Ltd., Sydney, NSW, Australia
- Oral Health Center, School of Dentistry, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD, Australia
- Institute for Glycomics, Griffith University Queensland, Southport, QLD, Australia
| | - Josue Murillo
- Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
| | - Nikita B. Ruparel
- Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
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18
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Xing WB, Wu ST, Wang XX, Li FY, Wang RX, He JH, Fu J, He Y. Potential of dental pulp stem cells and their products in promoting peripheral nerve regeneration and their future applications. World J Stem Cells 2023; 15:960-978. [PMID: 37970238 PMCID: PMC10631371 DOI: 10.4252/wjsc.v15.i10.960] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 10/07/2023] [Accepted: 10/23/2023] [Indexed: 10/26/2023] Open
Abstract
Peripheral nerve injury (PNI) seriously affects people's quality of life. Stem cell therapy is considered a promising new option for the clinical treatment of PNI. Dental stem cells, particularly dental pulp stem cells (DPSCs), are adult pluripotent stem cells derived from the neuroectoderm. DPSCs have significant potential in the field of neural tissue engineering due to their numerous advantages, such as easy isolation, multidifferentiation potential, low immunogenicity, and low transplant rejection rate. DPSCs are extensively used in tissue engineering and regenerative medicine, including for the treatment of sciatic nerve injury, facial nerve injury, spinal cord injury, and other neurodegenerative diseases. This article reviews research related to DPSCs and their advantages in treating PNI, aiming to summarize the therapeutic potential of DPSCs for PNI and the underlying mechanisms and providing valuable guidance and a foundation for future research.
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Affiliation(s)
- Wen-Bo Xing
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Shu-Ting Wu
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Xin-Xin Wang
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Fen-Yao Li
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Ruo-Xuan Wang
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Ji-Hui He
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Jiao Fu
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Yan He
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- Department of Stomatology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, Hubei Province, China.
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19
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Wang W, Xu Z, Liu M, Cai M, Liu X. Prospective applications of extracellular vesicle-based therapies in regenerative medicine: implications for the use of dental stem cell-derived extracellular vesicles. Front Bioeng Biotechnol 2023; 11:1278124. [PMID: 37936823 PMCID: PMC10627172 DOI: 10.3389/fbioe.2023.1278124] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 10/06/2023] [Indexed: 11/09/2023] Open
Abstract
In the 21st century, research on extracellular vesicles (EVs) has made remarkable advancements. Recently, researchers have uncovered the exceptional biological features of EVs, highlighting their prospective use as therapeutic targets, biomarkers, innovative drug delivery systems, and standalone therapeutic agents. Currently, mesenchymal stem cells stand out as the most potent source of EVs for clinical applications in tissue engineering and regenerative medicine. Owing to their accessibility and capability of undergoing numerous differentiation inductions, dental stem cell-derived EVs (DSC-EVs) offer distinct advantages in the field of tissue regeneration. Nonetheless, it is essential to note that unmodified EVs are currently unsuitable for use in the majority of clinical therapeutic scenarios. Considering the high feasibility of engineering EVs, it is imperative to modify these EVs to facilitate the swift translation of theoretical knowledge into clinical practice. The review succinctly presents the known biotherapeutic effects of odontogenic EVs and the underlying mechanisms. Subsequently, the current state of functional cargo loading for engineered EVs is critically discussed. For enhancing EV targeting and in vivo circulation time, the review highlights cutting-edge engineering solutions that may help overcome key obstacles in the clinical application of EV therapeutics. By presenting innovative concepts and strategies, this review aims to pave the way for the adaptation of DSC-EVs in regenerative medicine within clinical settings.
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Affiliation(s)
- Wenhao Wang
- School of Stomatology, Jinan University, Guangzhou, China
- Center of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Zinan Xu
- School of Stomatology, Jinan University, Guangzhou, China
- Center of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Minyi Liu
- Center of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, China
- Clinical Research Platform for Interdiscipline, Jinan University, Guangzhou, China
| | - Mingxiang Cai
- School of Stomatology, Jinan University, Guangzhou, China
- Center of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Xiangning Liu
- School of Stomatology, Jinan University, Guangzhou, China
- Center of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, China
- Clinical Research Platform for Interdiscipline, Jinan University, Guangzhou, China
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20
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Duncan HF, Kobayashi Y, Kearney M, Shimizu E. Epigenetic therapeutics in dental pulp treatment: Hopes, challenges and concerns for the development of next-generation biomaterials. Bioact Mater 2023; 27:574-593. [PMID: 37213443 PMCID: PMC10199232 DOI: 10.1016/j.bioactmat.2023.04.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 04/11/2023] [Accepted: 04/11/2023] [Indexed: 05/23/2023] Open
Abstract
This opinion-led review paper highlights the need for novel translational research in vital-pulp-treatment (VPT), but also discusses the challenges in translating evidence to clinics. Traditional dentistry is expensive, invasive and relies on an outmoded mechanical understanding of dental disease, rather than employing a biological perspective that harnesses cell activity and the regenerative-capacity. Recent research has focussed on developing minimally-invasive biologically-based 'fillings' that preserve the dental pulp; research that is shifting the paradigm from expensive high-technology dentistry, with high failure rates, to smart restorations targeted at biological processes. Current VPTs promote repair by recruiting odontoblast-like cells in a material-dependent process. Therefore, exciting opportunities exist for development of next-generation biomaterials targeted at regenerative processes in the dentin-pulp complex. This article analyses recent research using pharmacological-inhibitors to therapeutically-target histone-deacetylase (HDAC) enzymes in dental-pulp-cells (DPCs) that stimulate pro-regenerative effects with limited loss of viability. Consequently, HDAC-inhibitors have the potential to enhance biomaterial-driven tissue responses at low concentration by influencing the cellular processes with minimal side-effects, providing an opportunity to develop a topically-placed, inexpensive bio-inductive pulp-capping material. Despite positive results, clinical translation of these innovations requires enterprise to counteract regulatory obstacles, dental-industry priorities and to develop strong academic/industry partnerships. The aim of this opinion-led review paper is to discuss the potential role of therapeutically-targeting epigenetic modifications as part of a topical VPT strategy in the treatment of the damaged dental pulp, while considering the next steps, material considerations, challenges and future for the clinical development of epigenetic therapeutics or other 'smart' restorations in VPT.
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Affiliation(s)
- Henry F. Duncan
- Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin, University of Dublin, Lincoln Place, Dublin, Ireland
| | - Yoshifumi Kobayashi
- Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ, USA
| | - Michaela Kearney
- Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin, University of Dublin, Lincoln Place, Dublin, Ireland
| | - Emi Shimizu
- Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ, USA
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21
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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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22
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Ruan Q, Tan S, Guo L, Ma D, Wen J. Prevascularization techniques for dental pulp regeneration: potential cell sources, intercellular communication and construction strategies. Front Bioeng Biotechnol 2023; 11:1186030. [PMID: 37274160 PMCID: PMC10232868 DOI: 10.3389/fbioe.2023.1186030] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 05/10/2023] [Indexed: 06/06/2023] Open
Abstract
One of the difficulties of pulp regeneration is the rapid vascularization of transplanted engineered tissue, which is crucial for the initial survival of the graft and subsequent pulp regeneration. At present, prevascularization techniques, as emerging techniques in the field of pulp regeneration, has been proposed to solve this challenge and have broad application prospects. In these techniques, endothelial cells and pericytes are cocultured to induce intercellular communication, and the cell coculture is then introduced into the customized artificial vascular bed or induced to self-assembly to simulate the interaction between cells and extracellular matrix, which would result in construction of a prevascularization system, preformation of a functional capillary network, and rapid reconstruction of a sufficient blood supply in engineered tissue after transplantation. However, prevascularization techniques for pulp regeneration remain in their infancy, and there remain unresolved problems regarding cell sources, intercellular communication and the construction of prevascularization systems. This review focuses on the recent advances in the application of prevascularization techniques for pulp regeneration, considers dental stem cells as a potential cell source of endothelial cells and pericytes, discusses strategies for their directional differentiation, sketches the mechanism of intercellular communication and the potential application of communication mediators, and summarizes construction strategies for prevascularized systems. We also provide novel ideas for the extensive application and follow-up development of prevascularization techniques for dental pulp regeneration.
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Affiliation(s)
| | | | | | - Dandan Ma
- *Correspondence: Dandan Ma, ; Jun Wen,
| | - Jun Wen
- *Correspondence: Dandan Ma, ; Jun Wen,
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23
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Camassari JR, de Sousa ITC, Müller KC, Puppin-Rontani RM. The Self Assembling peptide P 11-4 influences viability and osteogenic differentiation of stem cells of the apical papilla (SCAP). J Dent 2023; 134:104551. [PMID: 37201776 DOI: 10.1016/j.jdent.2023.104551] [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: 02/06/2023] [Revised: 05/11/2023] [Accepted: 05/15/2023] [Indexed: 05/20/2023] Open
Abstract
OBJECTIVE to analyze the effect of P11-4 self-assembly peptide on cell viability and osteogenic capacity of SCAPs through mineral deposition and gene expression of osteogenic markers. . METHODS SCAPs were seeded in contact with P11-4 (10 µg/ml, 100 µg/ml and 1 mg/ml) solution. Cell viability was evaluated using a colorimetric assay MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) in an experimental time of 24, 48 and 72 h (n=7). Mineral deposition and quantification provided by the cells was tested using the Alizarin Red staining and Cetylpyridinium Chloride (CPC), respectively, after 30 days (n=4). Gene expression of Runt-related transcription factor 2 (RUNX2), Alkaline phosphatase (ALP) and Osteocalcin (OCN) was quantified using quantitative polymerase chain reaction (RT-qPCR), at 3 and 7 days with Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as the housekeeping gene, and relative gene expression was measured using the ΔΔCq method. Data were analyzed using Kruskall-Wallis followed by multiple comparisons, and T-test for gene expression with α=0.05. RESULTS All tested concentrations (10 µg/ml, 100 µg/ml and 1 mg/ml) were not cytotoxic at time 24 and 48 h. After 72 h, a slight decrease in cell viability was observed for the lowest concentration (10 µg/ml). The concentration of 100 µg/ml P11-4 showed the highest mineral deposition. However, qPCR analysis of P11-4 (10 µg/ml) showed upregulation of RUNX2 and OCN at 3 days, with downregulation of ALP at 3 and 7d. CONCLUSION P11-4 did not affect cell viability, induced mineral deposition in SCAPs, and upregulated the expression of RUNX2 and OCN genes at 3 days, while downregulating ALP expression at 3 and 7 days. CLINICAL SIGNIFICANCE Based on the results obtained in this study it can be stated that self-assembling peptide P11-4 is a potential candidate to induce mineralization on dental stem cells for regenerative purposes and also for a clinical use as a capping agent without compromising the cells health.
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Affiliation(s)
- Jessica Rodrigues Camassari
- PhD Student at Department of Restorative Dentistry, Dental Materials Division, University of Campinas, Av Limeira, 901. CEP 13.414-018, Piracicaba, São Paulo, Brazil
| | - Iago Torres Cortês de Sousa
- PhD Student at Department of Biosciences, Physiological Sciences Division, University of Campinas, Av Limeira, 901. CEP 13.414-018, Piracicaba, São Paulo, Brazil
| | - Karina Cogo Müller
- Full Professor of Pharmacology, Anesthesiology and Therapeutics Division, University of Campinas, Av Limeira, 901. CEP 13.414-018, Piracicaba, São Paulo, Brazil
| | - Regina Maria Puppin-Rontani
- Full Professor of Pediatric Dentistry, University State of Campinas, Av Limeira, 901. CEP 13.414-018, Piracicaba, São Paulo, Brazil.
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24
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Hammouda DA, Mansour AM, Saeed MA, Zaher AR, Grawish ME. Stem cell-derived exosomes for dentin-pulp complex regeneration: a mini-review. Restor Dent Endod 2023; 48:e20. [PMID: 37284341 PMCID: PMC10240090 DOI: 10.5395/rde.2023.48.e20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 03/12/2023] [Accepted: 03/22/2023] [Indexed: 06/08/2023] Open
Abstract
This mini-review was conducted to present an overview of the use of exosomes in regenerating the dentin-pulp complex (DPC). The PubMed and Scopus databases were searched for relevant articles published between January 1, 2013 and January 1, 2023. The findings of basic in vitro studies indicated that exosomes enhance the proliferation and migration of mesenchymal cells, as human dental pulp stem cells, via mitogen-activated protein kinases and Wingless-Int signaling pathways. In addition, they possess proangiogenic potential and contribute to neovascularization and capillary tube formation by promoting endothelial cell proliferation and migration of human umbilical vein endothelial cells. Likewise, they regulate the migration and differentiation of Schwann cells, facilitate the conversion of M1 pro-inflammatory macrophages to M2 anti-inflammatory phenotypes, and mediate immune suppression as they promote regulatory T cell conversion. Basic in vivo studies have indicated that exosomes triggered the regeneration of dentin-pulp-like tissue, and exosomes isolated under odontogenic circumstances are particularly strong inducers of tissue regeneration and stem cell differentiation. Exosomes are a promising regenerative tool for DPC in cases of small pulp exposure or for whole-pulp tissue regeneration.
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Affiliation(s)
- Dina A. Hammouda
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura, Egypt
| | - Alaa M Mansour
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura, Egypt
| | - Mahmoud A. Saeed
- Department of Oral Biology, Faculty of Dentistry, Menoufia University, Shibin el Kom, Egypt
| | - Ahmed R. Zaher
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura, Egypt
| | - Mohammed E. Grawish
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura, Egypt
- Department of Oral Biology, Faculty of Oral and Dental Medicine, Delta University for Science and Technology, Dakahlia, Egypt
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25
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Cell–scaffold interactions in tissue engineering for oral and craniofacial reconstruction. Bioact Mater 2023; 23:16-44. [DOI: 10.1016/j.bioactmat.2022.10.029] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/22/2022] [Accepted: 10/30/2022] [Indexed: 11/09/2022] Open
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26
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Noohi P, Abdekhodaie MJ, Saadatmand M, Nekoofar MH, Dummer PMH. The development of a dental light curable PRFe-loaded hydrogel as a potential scaffold for pulp-dentine complex regeneration: An in vitro study. Int Endod J 2023; 56:447-464. [PMID: 36546662 DOI: 10.1111/iej.13882] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 12/07/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022]
Abstract
AIM The study aimed to develop a bicomponent bioactive hydrogel formed in situ and enriched with an extract of platelet-rich fibrin (PRFe) and to assess its potential for use in pulp-dentine complex tissue engineering via cell homing. METHODOLOGY A bicomponent hydrogel based on photo-activated naturally derived polymers, methacrylated chitosan (ChitMA) and methacrylated collagen (ColMA), plus PRFe was fabricated. The optimized formulation of PRFe-loaded bicomponent hydrogel was determined by analysing the mechanical strength, swelling ratio and cell viability simultaneously. The physical, mechanical, rheological and morphological properties of the optimal hydrogel with and without PRFe were determined. Additionally, MTT, phalloidin/DAPI and live/dead assays were carried out to compare the viability, cytoskeletal morphology and migration ability of stem cells from the apical papilla (SCAP) within the developed hydrogels with and without PRFe, respectively. To further investigate the effect of PRFe on the differentiation of encapsulated SCAP, alizarin red S staining, RT-PCR analysis and immunohistochemical detection were performed. Statistical significance was established at p < .05. RESULTS The optimized formulation of PRFe-loaded bicomponent hydrogel can be rapidly photocrosslinked using available dental light curing units. Compared to bicomponent hydrogels without PRFe, the PRFe-loaded hydrogel exhibited greater viscoelasticity and higher cytocompatibility to SCAP. Moreover, it promoted cell proliferation and migration in vitro. It also supported the odontogenic differentiation of SCAP as evidenced by its promotion of biomineralization and upregulating the gene expression for ALP, COL I, DSPP and DMP1 as well as facilitated angiogenesis by enhancing VEGFA gene expression. CONCLUSIONS The new PRFe-loaded ChitMA/ColMA hydrogel developed within this study fulfils the criteria of injectability, cytocompatibility, chemoattractivity and bioactivity to promote odontogenic differentiation, which are fundamental requirements for scaffolds used in pulp-dentine complex regeneration via cell-homing approaches.
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Affiliation(s)
- Parisa Noohi
- Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran
| | - Mohammad J Abdekhodaie
- Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran.,Environmental and Applied Science Management, Yeates School of Graduate Studies, Toronto Metropolitan University, Toronto, Canada
| | - Maryam Saadatmand
- Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran
| | - Mohammad H Nekoofar
- Department of Endodontics, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran.,Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Department of Endodontics, Bahçeşehir University School of Dentistry, Istanbul, Turkey
| | - Paul M H Dummer
- School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
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27
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Lim H, Oh JS, Kang KR, Seo JY, Kim DK, Yu SK, Kim HJ, Park JC, Kim JS. 25-Hydroxycholesterol induces odontoclastic differentiation through RANK-RANKL upregulation and NF-κB activation in odontoblast-like MDPC-23 cells: An in vitro study. Int Endod J 2023; 56:432-446. [PMID: 36462163 DOI: 10.1111/iej.13878] [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: 06/28/2022] [Revised: 11/29/2022] [Accepted: 11/30/2022] [Indexed: 12/07/2022]
Abstract
AIM The physiological effects and cellular mechanism of 25-hydroxycholesterol (25-HC), which is an oxysterol synthesized from cholesterol by cholesterol-25-hydroxylase (CH25H) expressed under inflammatory conditions, are still largely unknown during odontoclastogenesis. This study aimed to evaluate 25-HC-induced odontoclastogenesis and its cellular mechanisms in odontoblast-like MDPC-23 cells. METHODOLOGY To investigate 25-HC-induced odontoclastogenesis of MDPC-23 cells and its cellular mechanism, haemotoxylin and eosin staining, tartrate-resistant acid phosphatase (TRAP) staining, dentine resorption assay, zymography, reactive oxygen species (ROS) detection, immunocytochemistry, and nuclear translocation were performed. The experimental values are presented as mean ± standard deviation and were compared using analysis of variance, followed by post hoc multiple comparisons (Tukey's test) using SPSS software version 22 (IBM Corp.). A p-value <.05 was considered statistically significant. RESULTS Lipopolysaccharide or receptor activator of nuclear factor-κB ligand (RANKL) induced the synthesis of 25-HC via the expression of CH25H in MDPC-23 cells (p < .01). Multinucleated giant cells with morphological characteristics and TRAP activity of the odontoclast were increased by 25-HC in MDPC-23 cells (p < .01). Moreover, 25-HC increased dentine resorption through the expression and activity of matrix metalloproteinases in MDPC-23 cells. It not only increased the expression of odontoclastogenic biomarkers but also translocated cytosolic nuclear factor-κB (NF-κB) to the nucleus in MDPC-23 cells. Additionally, 25-HC not only increased the production of ROS (p < .01), expression of inflammatory mediators (p < .01), pro-inflammatory cytokines, receptor activator of NF-κB (RANK), and RANKL but also suppressed the expression of osteoprotegerin (OPG) in MDPC-23 cells. In contrast, CDDO-Me, a chemical NF-κB inhibitor, decreased TRAP activity (p < .01) and downregulated the expression of the odontoclastogenic biomarkers, including RANK and RANKL, in MDPC-23 cells. CONCLUSION 25-HC induced odontoclastogenesis by modulating the RANK-RANKL-OPG axis via NF-κB activation in MDPC-23 cells. Therefore, these findings provide that 25-HC derived from cholesterol metabolism may be involved in the pathophysiological etiological factors of internal tooth resorption.
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Affiliation(s)
- HyangI Lim
- Institute of Dental Science, School of Dentistry, Chosun University, Gwangju, Korea
| | - Ji-Su Oh
- Institute of Dental Science, School of Dentistry, Chosun University, Gwangju, Korea.,Department of Oral and Maxillofacial Surgery, School of Dentistry, Chosun University, Gwangju, Korea
| | - Kyeong-Rok Kang
- Institute of Dental Science, School of Dentistry, Chosun University, Gwangju, Korea
| | - Jeong-Yeon Seo
- Institute of Dental Science, School of Dentistry, Chosun University, Gwangju, Korea
| | - Do Kyung Kim
- Institute of Dental Science, School of Dentistry, Chosun University, Gwangju, Korea
| | - Sun-Kyoung Yu
- Institute of Dental Science, School of Dentistry, Chosun University, Gwangju, Korea
| | - Heung-Joong Kim
- Institute of Dental Science, School of Dentistry, Chosun University, Gwangju, Korea
| | - Joo-Cheol Park
- Laboratory for the Study of Regenerative Dental Medicine, Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea
| | - Jae-Sung Kim
- Institute of Dental Science, School of Dentistry, Chosun University, Gwangju, Korea
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28
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Piglionico SS, Pons C, Romieu O, Cuisinier F, Levallois B, Panayotov IV. In vitro, ex vivo, and in vivo models for dental pulp regeneration. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2023; 34:15. [PMID: 37004591 PMCID: PMC10067643 DOI: 10.1007/s10856-023-06718-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 03/13/2023] [Indexed: 05/03/2023]
Abstract
Based on the concept of tissue engineering (Cells-Scaffold-Bioactive molecules), regenerative endodontics appeared as a new notion for dental endodontic treatment. Its approaches aim to preserve dental pulp vitality (pulp capping) or to regenerate a vascularized pulp-like tissue inside necrotic root canals by cell homing. To improve the methods of tissue engineering for pulp regeneration, numerous studies using in vitro, ex vivo, and in vivo models have been performed. This review explores the evolution of laboratory models used in such studies and classifies them according to different criteria. It starts from the initial two-dimensional in vitro models that allowed characterization of stem cell behavior, through 3D culture matrices combined with dental tissue and finally arrives at the more challenging ex vivo and in vivo models. The travel which follows the elaboration of such models reveals the difficulty in establishing reproducible laboratory models for dental pulp regeneration. The development of well-established protocols and new laboratory ex vivo and in vivo models in the field of pulp regeneration would lead to consistent results, reduction of animal experimentation, and facilitation of the translation to clinical practice.
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Affiliation(s)
- Sofia Silvia Piglionico
- LBN, Univ. Montpellier, Montpellier, France.
- Centro de Investigaciones Odontológicas, National University of Cuyo, Mendoza, Argentina.
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29
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Zhao J, Zhou YH, Zhao YQ, Gao ZR, Ouyang ZY, Ye Q, Liu Q, Chen Y, Tan L, Zhang SH, Feng Y, Hu J, Dusenge MA, Feng YZ, Guo Y. Oral cavity-derived stem cells and preclinical models of jaw-bone defects for bone tissue engineering. Stem Cell Res Ther 2023; 14:39. [PMID: 36927449 PMCID: PMC10022059 DOI: 10.1186/s13287-023-03265-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Accepted: 03/06/2023] [Indexed: 03/18/2023] Open
Abstract
BACKGROUND Jaw-bone defects caused by various diseases lead to aesthetic and functional complications, which can seriously affect the life quality of patients. Current treatments cannot fully meet the needs of reconstruction of jaw-bone defects. Thus, the research and application of bone tissue engineering are a "hot topic." As seed cells for engineering of jaw-bone tissue, oral cavity-derived stem cells have been explored and used widely. Models of jaw-bone defect are excellent tools for the study of bone defect repair in vivo. Different types of bone defect repair require different stem cells and bone defect models. This review aimed to better understand the research status of oral and maxillofacial bone regeneration. MAIN TEXT Data were gathered from PubMed searches and references from relevant studies using the search phrases "bone" AND ("PDLSC" OR "DPSC" OR "SCAP" OR "GMSC" OR "SHED" OR "DFSC" OR "ABMSC" OR "TGPC"); ("jaw" OR "alveolar") AND "bone defect." We screened studies that focus on "bone formation of oral cavity-derived stem cells" and "jaw bone defect models," and reviewed the advantages and disadvantages of oral cavity-derived stem cells and preclinical model of jaw-bone defect models. CONCLUSION The type of cell and animal model should be selected according to the specific research purpose and disease type. This review can provide a foundation for the selection of oral cavity-derived stem cells and defect models in tissue engineering of the jaw bone.
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Affiliation(s)
- Jie Zhao
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Ying-Hui Zhou
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.,National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Ya-Qing Zhao
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Zheng-Rong Gao
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Ze-Yue Ouyang
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Qin Ye
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Qiong Liu
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Yun Chen
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Li Tan
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Shao-Hui Zhang
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Yao Feng
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Jing Hu
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Marie Aimee Dusenge
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Yun-Zhi Feng
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.
| | - Yue Guo
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.
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Azaryan E, Emadian Razavi F, Hanafi-Bojd MY, Alemzadeh E, Naseri M. Dentin regeneration based on tooth tissue engineering: A review. Biotechnol Prog 2023; 39:e3319. [PMID: 36522133 DOI: 10.1002/btpr.3319] [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: 06/14/2022] [Revised: 11/22/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022]
Abstract
Missing or damaged teeth due to caries, genetic disorders, oral cancer, or infection may contribute to physical and mental impairment that reduces the quality of life. Despite major progress in dental tissue repair and those replacing missing teeth with prostheses, clinical treatments are not yet entirely satisfactory, as they do not regenerate tissues with natural teeth features. Therefore, much of the focus has centered on tissue engineering (TE) based on dental stem/progenitor cells to create bioengineered dental tissues. Many in vitro and in vivo studies have shown the use of cells in regenerating sections of a tooth or a whole tooth. Tooth tissue engineering (TTE), as a promising method for dental tissue regeneration, can form durable biological substitutes for soft and mineralized dental tissues. The cell-based TE approach, which directly seeds cells and bioactive components onto the biodegradable scaffolds, is currently the most potential method. Three essential components of this strategy are cells, scaffolds, and growth factors (GFs). This study investigates dentin regeneration after an injury such as caries using TE and stem/progenitor cell-based strategies. We begin by discussing about the biological structure of a dentin and dentinogenesis. The engineering of teeth requires knowledge of the processes that underlie the growth of an organ or tissue. Then, the three fundamental requirements for dentin regeneration, namely cell sources, GFs, and scaffolds are covered in the current study, which may ultimately lead to new insights in this field.
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Affiliation(s)
- Ehsaneh Azaryan
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
- Cellular and Molecular Research Center, Department of Molecular Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Fariba Emadian Razavi
- Dental Research Center, Faculty of Dentistry, Birjand University of Medical Sciences, Birjand, Iran
| | - Mohammad Yahya Hanafi-Bojd
- Cellular and Molecular Research Center, Birjand University of Medical sciences, Birjand, Iran
- Department of Pharmaceutics and Pharmaceutical nanotechnology, School of Pharmacy, Birjand University of Medical Sciences, Birjand, Iran
| | - Esmat Alemzadeh
- Department of Medical Biotechnology, Faculty of medicine, Birjand University of Medical Sciences, Birjand, Iran
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Mohsen Naseri
- Cellular and Molecular Research Center, Department of Molecular Medicine, Birjand University of Medical Sciences, Birjand, Iran
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Mahdavi-Jouibari F, Parseh B, Kazeminejad E, Khosravi A. Hopes and opportunities of stem cells from human exfoliated deciduous teeth (SHED) in cartilage tissue regeneration. Front Bioeng Biotechnol 2023; 11:1021024. [PMID: 36860887 PMCID: PMC9968979 DOI: 10.3389/fbioe.2023.1021024] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 01/30/2023] [Indexed: 02/17/2023] Open
Abstract
Cartilage lesions are common conditions, affecting elderly and non-athletic populations. Despite recent advances, cartilage regeneration remains a major challenge today. The absence of an inflammatory response following damage and the inability of stem cells to penetrate into the healing site due to the absence of blood and lymph vessels are assumed to hinder joint repair. Stem cell-based regeneration and tissue engineering have opened new horizons for treatment. With advances in biological sciences, especially stem cell research, the function of various growth factors in the regulation of cell proliferation and differentiation has been established. Mesenchymal stem cells (MSCs) isolated from different tissues have been shown to increase into therapeutically relevant cell numbers and differentiate into mature chondrocytes. As MSCs can differentiate and become engrafted inside the host, they are considered suitable candidates for cartilage regeneration. Stem cells from human exfoliated deciduous teeth (SHED) provide a novel and non-invasive source of MSCs. Due to their simple isolation, chondrogenic differentiation potential, and minimal immunogenicity, they can be an interesting option for cartilage regeneration. Recent studies have reported that SHED-derived secretome contains biomolecules and compounds that efficiently promote regeneration in damaged tissues, including cartilage. Overall, this review highlighted the advances and challenges of cartilage regeneration using stem cell-based therapies by focusing on SHED.
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Affiliation(s)
- Forough Mahdavi-Jouibari
- Department of Medical Biotechnology, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran
| | - Benyamin Parseh
- Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran,Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran
| | - Ezatolah Kazeminejad
- Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran,Dental Research Center, Golestan University of Medical Sciences, Gorgan, Iran,*Correspondence: Ezatolah Kazeminejad, Dr. ; Ayyoob Khosravi,
| | - Ayyoob Khosravi
- Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran,Department of Molecular Medicine, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran,*Correspondence: Ezatolah Kazeminejad, Dr. ; Ayyoob Khosravi,
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Nair K, Bhat AR. Applications of Gene Therapy in Dentistry: A Review Article. JOURNAL OF HEALTH AND ALLIED SCIENCES NU 2023. [DOI: 10.1055/s-0042-1759711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
AbstractGene therapy promises to possess a good prospect in bridging the gap between dental applications and medicine. The dynamic therapeutic modalities of gene therapy have been advancing rapidly. Conventional approaches are being revamped to be more comprehensive and pre-emptive, which could do away with the need for surgery and medicine altogether. The complementary base sequences known as genes convey the instructions required to manufacture proteins. The oral cavity is one of the most accessible locations for the therapeutic intervention of gene therapy for several oral tissues. In 1990, the first significant trial of gene therapy was overseen to alleviate adenosine deaminase deficiency. The notion of genetic engineering has become increasingly appealing as a reflection of its benefits over conventional treatment modalities. An example of how this technology may alter dentistry is the implementation of gene therapy for dental and oral ailments. The objective of this article is to examine the effects of gene therapy on the field of dentistry, periodontology and implantology. Furthermore, the therapeutic factors of disease therapy, minimal invasion, and appropriate outcome have indeed been taken into consideration.
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Affiliation(s)
- Karthika Nair
- Department of Periodontology, A B Shetty Memorial Institute of Dental Sciences, NITTE Deemed to be University, Mangaluru, Karnataka, India
| | - Amitha Ramesh Bhat
- Department of Periodontology, A B Shetty Memorial Institute of Dental Sciences, NITTE Deemed to be University, Mangaluru, Karnataka, India
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Liu C, Sharpe P, Volponi AA. Applications of regenerative techniques in adult orthodontics. FRONTIERS IN DENTAL MEDICINE 2023. [DOI: 10.3389/fdmed.2022.1100548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Management of the growing adult orthodontic patient population must contend with challenges particular to orthodontic treatment in adults. These include a limited rate of tooth movement, increased incidence of periodontal complications, higher risk of iatrogenic root resorption and pulp devitalisation, resorbed edentulous ridges, and lack of growth potential. The field of regenerative dentistry has evolved numerous methods of manipulating cellular and molecular processes to rebuild functional oral and dental tissues, and research continues to advance our understanding of stem cells, signalling factors that stimulate repair and extracellular scaffold interactions for the purposes of tissue engineering. We discuss recent findings in the literature to synthesise our understanding of current and prospective approaches based on biological repair that have the potential to improve orthodontic treatment outcomes in adult patients. Methods such as mesenchymal stem cell transplantation, biomimetic scaffold manipulation, and growth factor control may be employed to overcome the challenges described above, thereby reducing adverse sequelae and improving orthodontic treatment outcomes in adult patients. The overarching goal of such research is to eventually translate these regenerative techniques into clinical practice, and establish a new gold standard of safe, effective, autologous therapies.
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Hu N, Li W, Jiang W, Wen J, Gu S. Creating a Microenvironment to Give Wings to Dental Pulp Regeneration-Bioactive Scaffolds. Pharmaceutics 2023; 15:158. [PMID: 36678787 PMCID: PMC9861529 DOI: 10.3390/pharmaceutics15010158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/13/2022] [Accepted: 12/23/2022] [Indexed: 01/05/2023] Open
Abstract
Dental pulp and periapical diseases make patients suffer from acute pain and economic loss. Although root canal therapies, as demonstrated through evidence-based medicine, can relieve symptoms and are commonly employed by dentists, it is still difficult to fully restore a dental pulp's nutrition, sensory, and immune-regulation functions. In recent years, researchers have made significant progress in tissue engineering to regenerate dental pulp in a desired microenvironment. With breakthroughs in regenerative medicine and material science, bioactive scaffolds play a pivotal role in creating a suitable microenvironment for cell survival, proliferation, and differentiation, following dental restoration and regeneration. This article focuses on current challenges and novel perspectives about bioactive scaffolds in creating a microenvironment to promote dental pulp regeneration. We hope our readers will gain a deeper understanding and new inspiration of dental pulp regeneration through our summary.
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Affiliation(s)
- Nan Hu
- Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai 200011, China
- National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Weiping Li
- National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
- Department of Oral and Maxillofacial Head & Neck Oncology, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Wentao Jiang
- Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai 200011, China
- National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Jin Wen
- National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
- Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai 200011, China
- Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai 200125, China
| | - Shensheng Gu
- Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai 200011, China
- National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
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Fracaro L, Hochuli AHD, Selenko AH, Capriglione LGA, Brofman PRS, Senegaglia AC. Mesenchymal stromal cells derived from exfoliated deciduous teeth express neuronal markers before differentiation induction. J Appl Oral Sci 2023; 31:e20220489. [PMID: 37075387 PMCID: PMC10118381 DOI: 10.1590/1678-7757-2022-0489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 03/09/2023] [Indexed: 04/21/2023] Open
Abstract
OBJECTIVE This study aimed to evaluate neuronal markers in stromal cells from human exfoliated deciduous teeth (SHED) and standardize the isolation and characterization of those cells. METHODOLOGY Healthy primary teeth were collected from children. The cells were isolated by enzymatic digestion with collagenase. By following the International Society for Cell and Gene Therapy (ISCT) guidelines, SHED were characterized by flow cytometry and differentiated into osteogenic, adipogenic, and chondrogenic lineages. Colony-forming unit-fibroblasts (CFU-F) were performed to assess these cells' potential and efficiency. To clarify the neuronal potential of SHED, the expression of nestin and βIII-tubulin were examined by immunofluorescence and SOX1, SOX2, GFAP, and doublecortin (DCX), nestin, CD56, and CD146 by flow cytometry. RESULTS SHED showed mesenchymal stromal cells characteristics, such as adhesion to plastic, positive immunophenotypic profile for CD29, CD44, CD73, CD90, CD105, and CD166 markers, reduced expression for CD14, CD19, CD34, CD45, HLA-DR, and differentiation in three lineages confirmed by staining and gene expression for adipogenic differentiation. The average efficiency of colony formation was 16.69%. SHED expressed the neuronal markers nestin and βIII-tubulin; the fluorescent signal intensity was significantly higher in βIII-tubulin (p<0.0001) compared to nestin. Moreover, SHED expressed DCX, GFAP, nestin, SOX1, SOX2, CD56, CD146, and CD271. Therefore, SHED had a potential for neuronal lineage even without induction with culture medium and specific factors. CONCLUSION SHEDs may be a new therapeutic strategy for regenerating and repairing neuronal cells and tissues.
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Affiliation(s)
- Letícia Fracaro
- Pontificia Universidade Católica do Paraná, School of Medicine and Life Sciences - Core for Cell Technology, Curitiba, PR, Brasil
| | - Agner Henrique Dorigo Hochuli
- Pontificia Universidade Católica do Paraná, School of Medicine and Life Sciences - Core for Cell Technology, Curitiba, PR, Brasil
| | - Ana Helena Selenko
- Pontificia Universidade Católica do Paraná, School of Medicine and Life Sciences - Core for Cell Technology, Curitiba, PR, Brasil
| | | | - Paulo Roberto Slud Brofman
- Pontificia Universidade Católica do Paraná, School of Medicine and Life Sciences - Core for Cell Technology, Curitiba, PR, Brasil
| | - Alexandra Cristina Senegaglia
- Pontificia Universidade Católica do Paraná, School of Medicine and Life Sciences - Core for Cell Technology, Curitiba, PR, Brasil
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ANIL SUKUMARAN, RAMADOSS RAMYA, G. THOMAS NEBU, M. GEORGE JASMIN, K. SWEETY VISHNUPRIYA. Dental pulp stem cells and banking of teeth as a lifesaving therapeutic vista. BIOCELL 2023; 47:71-80. [DOI: 10.32604/biocell.2023.024334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Najafi-Ghalehlou N, Feizkhah A, Mobayen M, Pourmohammadi-Bejarpasi Z, Shekarchi S, Roushandeh AM, Roudkenar MH. Plumping up a Cushion of Human Biowaste in Regenerative Medicine: Novel Insights into a State-of-the-Art Reserve Arsenal. Stem Cell Rev Rep 2022; 18:2709-2739. [PMID: 35505177 PMCID: PMC9064122 DOI: 10.1007/s12015-022-10383-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/25/2022] [Indexed: 12/03/2022]
Abstract
Major breakthroughs and disruptive methods in disease treatment today owe their thanks to our inch by inch developing conception of the infinitive aspects of medicine since the very beginning, among which, the role of the regenerative medicine can on no account be denied, a branch of medicine dedicated to either repairing or replacing the injured or diseased cells, organs, and tissues. A novel means to accomplish such a quest is what is being called "medical biowaste", a large assortment of biological samples produced during a surgery session or as a result of physiological conditions and biological activities. The current paper accentuating several of a number of promising sources of biowaste together with their plausible applications in routine clinical practices and the confronting challenges aims at inspiring research on the existing gap between clinical and basic science to further extend our knowledge and understanding concerning the potential applications of medical biowaste.
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Affiliation(s)
- Nima Najafi-Ghalehlou
- Department of Medical Laboratory Sciences, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Feizkhah
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammadreza Mobayen
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Zahra Pourmohammadi-Bejarpasi
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Shima Shekarchi
- Anatomical Sciences Department, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Amaneh Mohammadi Roushandeh
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran.
| | - Mehryar Habibi Roudkenar
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran.
- Cardiovascular Diseases Research Center, Department of Cardiology, School of Medicine, Heshmat Hospital, Guilan University of Medical Sciences, Rasht, Iran.
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Ohlsson E, Galler KM, Widbiller M. A Compilation of Study Models for Dental Pulp Regeneration. Int J Mol Sci 2022; 23:ijms232214361. [PMID: 36430838 PMCID: PMC9695686 DOI: 10.3390/ijms232214361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 11/12/2022] [Accepted: 11/14/2022] [Indexed: 11/22/2022] Open
Abstract
Efforts to heal damaged pulp tissue through tissue engineering have produced positive results in pilot trials. However, the differentiation between real regeneration and mere repair is not possible through clinical measures. Therefore, preclinical study models are still of great importance, both to gain insights into treatment outcomes on tissue and cell levels and to develop further concepts for dental pulp regeneration. This review aims at compiling information about different in vitro and in vivo ectopic, semiorthotopic, and orthotopic models. In this context, the differences between monolayer and three-dimensional cell cultures are discussed, a semiorthotopic transplantation model is introduced as an in vivo model for dental pulp regeneration, and finally, different animal models used for in vivo orthotopic investigations are presented.
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Affiliation(s)
- Ella Ohlsson
- Department of Operative Dentistry and Periodontology, Friedrich-Alexander-University Erlangen-Nuernberg, D-91054 Erlangen, Germany
| | - Kerstin M. Galler
- Department of Operative Dentistry and Periodontology, Friedrich-Alexander-University Erlangen-Nuernberg, D-91054 Erlangen, Germany
| | - Matthias Widbiller
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, D-93053 Regensburg, Germany
- Correspondence:
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Liu J, Watanabe K, Dabdoub SM, Lee BS, Kim DG. Site-specific characteristics of bone and progenitor cells in control and ovariectomized rats. Bone 2022; 163:116501. [PMID: 35872108 DOI: 10.1016/j.bone.2022.116501] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 07/11/2022] [Accepted: 07/18/2022] [Indexed: 11/25/2022]
Abstract
One-third of postmenopausal women experience at least one osteoporotic bone fracture in their lifetime that occurs spontaneously or from low-impact events. However, osteoporosis-associated jaw bone fractures are extremely rare. It was also observed that jaw bone marrow stem cells (BMSCs) have a higher capacity to form mineralized tissues than limb BMSCs. At present, the underlying causes and mechanisms of variations between jaw bone and limb bone during postmenopause are largely unknown. Thus, the objective of the current study was to examine the site-specific effects of estrogen deficiency using comprehensive analysis of bone quantity and quality, and its association with characterization of cellular components of bone. Nine rats (female, 6 months old) for each bilateral sham and ovariectomy (OVX) surgery were obtained and maintained for 2 months after surgery. A hemi-mandible and a femur from each rat were characterized for parameters of volume, mineral density, cortical and trabecular morphology, and static and dynamic mechanical analysis. Another set of 5 rats (female, 9 months old) was obtained for assays of BMSCs. Following cytometry to identify BMSCs, bioassays for proliferation, and osteogenic, adipogenic, chondrogenic differentiation, and cell mitochondrial stress tests were performed. In addition, mRNA expression of BMSCs was analyzed. OVX decreased bone quantity and quality (mineral content, morphology, and energy dissipation) of femur while those of mandible were not influenced. Cellular assays demonstrated that mandible BMSCs showed greater differentiation than femur BMSCs. Gene ontology pathway analysis indicated that the mandibular BMSCs showed most significant differential expression of genes in the regulatory pathways of osteoblast differentiation, SMAD signaling, cartilage development, and glucose transmembrane transporter activity. These findings suggested that active mandibular BMSCs maintain bone formation and mineralization by balancing the rapid bone resorption caused by estrogen deficiency. These characteristics likely help reduce the risk of osteoporotic fracture in postmenopausal jawbone.
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Affiliation(s)
- Jie Liu
- Division of Orthodontics, College of Dentistry, The Ohio State University, Columbus, OH 43210, USA
| | - Keiichiro Watanabe
- Division of Orthodontics, College of Dentistry, The Ohio State University, Columbus, OH 43210, USA
| | - Shareef M Dabdoub
- Division of Biostatistics and Computational Biology, Department of Periodontics, College of Dentistry and Dental Clinics, The University of Iowa, Iowa City, IA 52242, USA.
| | - Beth S Lee
- Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
| | - Do-Gyoon Kim
- Division of Orthodontics, College of Dentistry, The Ohio State University, Columbus, OH 43210, USA.
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Ahuja A, Tyagi PK, Kumar M, Sharma N, Prakash S, Radha, Chandran D, Dhumal S, Rais N, Singh S, Dey A, Senapathy M, Saleena LAK, Shanavas A, Mohankumar P, Rajalingam S, Murugesan Y, Vishvanathan M, Sathyaseelan SK, Viswanathan S, Kumar KK, Natta S, Mekhemar M. Botanicals and Oral Stem Cell Mediated Regeneration: A Paradigm Shift from Artificial to Biological Replacement. Cells 2022; 11:2792. [PMID: 36139367 PMCID: PMC9496740 DOI: 10.3390/cells11182792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 09/03/2022] [Accepted: 09/04/2022] [Indexed: 11/23/2022] Open
Abstract
Stem cells are a well-known autologous pluripotent cell source, having excellent potential to develop into specialized cells, such as brain, skin, and bone marrow cells. The oral cavity is reported to be a rich source of multiple types of oral stem cells, including the dental pulp, mucosal soft tissues, periodontal ligament, and apical papilla. Oral stem cells were useful for both the regeneration of soft tissue components in the dental pulp and mineralized structure regeneration, such as bone or dentin, and can be a viable substitute for traditionally used bone marrow stem cells. In recent years, several studies have reported that plant extracts or compounds promoted the proliferation, differentiation, and survival of different oral stem cells. This review is carried out by following the PRISMA guidelines and focusing mainly on the effects of bioactive compounds on oral stem cell-mediated dental, bone, and neural regeneration. It is observed that in recent years studies were mainly focused on the utilization of oral stem cell-mediated regeneration of bone or dental mesenchymal cells, however, the utility of bioactive compounds on oral stem cell-mediated regeneration requires additional assessment beyond in vitro and in vivo studies, and requires more randomized clinical trials and case studies.
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Affiliation(s)
- Anami Ahuja
- Department of Biotechnology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow 226031, India
- Department of Biotechnology, Meerut Institute of Engineering and Technology, Meerut 250005, India
| | - Pankaj Kumar Tyagi
- Department of Biotechnology, Noida Institute of Engineering & Technology, Greater Noida 201306, India
| | - Manoj Kumar
- Chemical and Biochemical Processing Division, ICAR–Central Institute for Research on Cotton Technology, Mumbai 400019, India
| | - Naveen Sharma
- Division of Biomedical Informatics, Indian Council of Medical Research, New Delhi 110029, India
| | - Suraj Prakash
- School of Biological and Environmental Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229, India
| | - Radha
- School of Biological and Environmental Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229, India
| | - Deepak Chandran
- Department of Veterinary Sciences and Animal Husbandry, Amrita School of Agricultural Sci-ences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Sangram Dhumal
- Division of Horticulture, RCSM College of Agriculture, Kolhapur 416004, India
| | - Nadeem Rais
- Department of Pharmacy, Bhagwant University, Ajmer 305004, India
| | - Surinder Singh
- Dr. S. S. Bhatnagar University Institute of Chemical Engineering and Technology, Panjab University, Chandigarh 160014, India
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata 700073, India
| | - Marisennayya Senapathy
- Department of Rural Development and Agricultural Extension, College of Agriculture, Wolaita Sodo University, Wolaita Sodo P.O. Box 138, Ethiopia
| | - Lejaniya Abdul Kalam Saleena
- Department of Food Science and Nutrition, Faculty of Applied Sciences, UCSI University, Kuala Lampur 56000, Malaysia
| | - Arjun Shanavas
- Division of Medicine, Indian Veterinary Research Institute, Bareilly 243122, India
| | - Pran Mohankumar
- School of Agriculture and Biosciences, Karunya Institute of Technology and Sciences, Coimbatore 641114, India
| | - Sureshkumar Rajalingam
- Department of Agronomy, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Yasodha Murugesan
- Department of Agronomy, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Marthandan Vishvanathan
- Department of Seed Science and Technology, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | | | - Sabareeshwari Viswanathan
- Department of Soil Science and Agricultural Chemistry, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Keerthana Krishna Kumar
- Department of Soil Science and Agricultural Chemistry, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Suman Natta
- ICAR—National Research Centre for Orchids, Pakyong 737106, India
| | - Mohamed Mekhemar
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Chris-tian-Albrecht’s University, 24105 Kiel, Germany
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Sugiaman VK, Djuanda R, Pranata N, Naliani S, Demolsky WL. Tissue Engineering with Stem Cell from Human Exfoliated Deciduous Teeth (SHED) and Collagen Matrix, Regulated by Growth Factor in Regenerating the Dental Pulp. Polymers (Basel) 2022; 14:polym14183712. [PMID: 36145860 PMCID: PMC9503223 DOI: 10.3390/polym14183712] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 08/25/2022] [Accepted: 09/02/2022] [Indexed: 11/16/2022] Open
Abstract
Maintaining dental pulp vitality and preventing tooth loss are two challenges in endodontic treatment. A tooth lacking a viable pulp loses its defense mechanism and regenerative ability, making it more vulnerable to severe damage and eventually necessitating extraction. The tissue engineering approach has drawn attention as an alternative therapy as it can regenerate dentin-pulp complex structures and functions. Stem cells or progenitor cells, extracellular matrix, and signaling molecules are triad components of this approach. Stem cells from human exfoliated deciduous teeth (SHED) are a promising, noninvasive source of stem cells for tissue regeneration. Not only can SHEDs regenerate dentin-pulp tissues (comprised of fibroblasts, odontoblasts, endothelial cells, and nerve cells), but SHEDs also possess immunomodulatory and immunosuppressive properties. The collagen matrix is a material of choice to provide structural and microenvironmental support for SHED-to-dentin pulp tissue differentiation. Growth factors regulate cell proliferation, migration, and differentiation into specific phenotypes via signal-transduction pathways. This review provides current concepts and applications of the tissue engineering approach, especially SHEDs, in endodontic treatment.
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Affiliation(s)
- Vinna K Sugiaman
- Department of Oral Biology, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Rudy Djuanda
- Department of Conservative Dentistry and Endodontic, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Natallia Pranata
- Department of Oral Biology, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Silvia Naliani
- Department of Prosthodontics, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Wayan L Demolsky
- Department of Oral Biology, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
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Noohi P, Abdekhodaie MJ, Nekoofar MH, Galler KM, Dummer PMH. Advances in Scaffolds Used for Pulp-Dentine Complex Tissue Engineering - A Narrative Review. Int Endod J 2022; 55:1277-1316. [PMID: 36039729 DOI: 10.1111/iej.13826] [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: 01/27/2022] [Revised: 07/28/2022] [Accepted: 08/10/2022] [Indexed: 11/27/2022]
Abstract
Pulp necrosis in immature teeth disrupts root development and predisposes roots to fracture as a consequence of their thin walls and open apices. Regenerative endodontics is a developing treatment modality whereby necrotic pulps are replaced with newly formed healthy tissue inside the root canal. Many clinical studies have demonstrated the potential of this strategy to stimulate root maturation and apical root-end closure. However, clinical outcomes are patient-dependent and unpredictable. The development of predictable clinical protocols is achieved through the interplay of the three classical elements of tissue engineering, namely, stem cells, signaling molecules, and scaffolds. Scaffolds provide structural support for cells to adhere and proliferate and also regulate cell differentiation and metabolism. Hence, designing and fabricating an appropriate scaffold is a crucial step in tissue engineering. In this review, four main classes of scaffolds used to engineer pulp-dentine complexes, including bioceramic-based scaffolds, synthetic polymer-based scaffolds, natural polymer-based scaffolds, and composite scaffolds, are covered. Additionally, recent advances in the design, fabrication, and application of such scaffolds are analysed along with their advantages and limitations. Finally, the importance of vascular network establishment in the success of pulp-dentine complex regeneration and strategies used to create scaffolds to address this challenge are discussed.
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Affiliation(s)
- Parisa Noohi
- Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran
| | - Mohammad J Abdekhodaie
- Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran
| | - Mohammad H Nekoofar
- Department of Endodontics, School of Dentistry, Tehran University of Medical Sciences Tehran University of Medical Sciences, Tehran, Iran.,Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Department of Endodontic, Bahçeşehir University School of Dentistry, Istanbul, Turkey
| | - Kerstin M Galler
- Department of Conservative Dentistry and Periodontology, University Hospital Erlangen-Nürnberg, Erlangen, Germany
| | - Paul M H Dummer
- School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
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Wang D, Zhu N, Xie F, Qin M, Wang Y. Long non-coding RNA IGFBP7-AS1 accelerates the odontogenic differentiation of stem cells from human exfoliated deciduous teeth by regulating IGFBP7 expression. Hum Cell 2022; 35:1697-1707. [PMID: 36038801 PMCID: PMC9515061 DOI: 10.1007/s13577-022-00763-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 07/27/2022] [Indexed: 11/29/2022]
Abstract
Stem cells from human exfoliated deciduous teeth (SHED) are attractive seed cells for dental tissue engineering. We identified the effect of the long noncoding RNA insulin-like growth factor-binding protein 7 antisense RNA 1 (lncRNA IGFBP7-AS1) in vivo and its underlying mechanism during SHED odontogenic differentiation. IGFBP7-AS1 and insulin-like growth factor-binding protein 7 (IGFBP7) were overexpressed using lentiviruses. IGFBP7 expression was knocked down with small interfering RNA. The effect of IGFBP7-AS1 in vivo was confirmed by animal experiments. The effect of IGFBP7 on SHED odontogenic differentiation was assessed with alkaline phosphatase staining, alizarin red S staining, quantitative reverse transcription-PCR, and western blotting. The relationship between IGFBP7-AS1 and IGFBP7 was confirmed by quantitative reverse transcription–PCR and western blotting. IGFBP7-AS1 promoted SHED odontogenesis in vivo, and regulated the expression of the coding gene IGFBP7 positively. Inhibiting IGFBP7 led to suppress SHED odontogenic differentiation while IGFBP7 overexpression had the opposite effect. IGFBP7-AS1 enhanced the stability of IGFBP7. IGFBP7-AS1 promoted SHED odontogenic differentiation in vivo. The underlying mechanism may involve the enhancement of IGFBP7 stability. This may provide novel potential targets for dental tissue engineering.
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Affiliation(s)
- Dan Wang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Peking University, #22 Zhongguancun South Avenue Nandajie, Haidian District, Beijing, 100081, China
| | - Ningxin Zhu
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Peking University, #22 Zhongguancun South Avenue Nandajie, Haidian District, Beijing, 100081, China
| | - Fei Xie
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Peking University, #22 Zhongguancun South Avenue Nandajie, Haidian District, Beijing, 100081, China
| | - Man Qin
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Peking University, #22 Zhongguancun South Avenue Nandajie, Haidian District, Beijing, 100081, China
| | - Yuanyuan Wang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, Peking University, #22 Zhongguancun South Avenue Nandajie, Haidian District, Beijing, 100081, China.
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Kobayashi Y, Nouet J, Baljinnyam E, Siddiqui Z, Fine DH, Fraidenraich D, Kumar VA, Shimizu E. iPSC-derived cranial neural crest-like cells can replicate dental pulp tissue with the aid of angiogenic hydrogel. Bioact Mater 2022; 14:290-301. [PMID: 35310357 PMCID: PMC8897656 DOI: 10.1016/j.bioactmat.2021.11.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 11/07/2021] [Accepted: 11/09/2021] [Indexed: 12/18/2022] Open
Abstract
The dental pulp has irreplaceable roles in maintaining healthy teeth and its regeneration is a primary aim of regenerative endodontics. This study aimed to replicate the characteristics of dental pulp tissue by using cranial neural crest (CNC)-like cells (CNCLCs); these cells were generated by modifying several steps of a previously established method for deriving NC-like cells from induced pluripotent stem cells (iPSCs). CNC is the anterior region of the neural crest in vertebrate embryos, which contains the primordium of dental pulp cells or odontoblasts. The produced CNCLCs showed approximately 2.5–12,000-fold upregulations of major CNC marker genes. Furthermore, the CNCLCs exhibited remarkable odontoblastic differentiation ability, especially when treated with a combination of the fibroblast growth factors (FGFs) FGF4 and FGF9. The FGFs induced odontoblast marker genes by 1.7–5.0-fold, as compared to bone morphogenetic protein 4 (BMP4) treatment. In a mouse subcutaneous implant model, the CNCLCs briefly fated with FGF4 + FGF9 replicated dental pulp tissue characteristics, such as harboring odontoblast-like cells, a dentin-like layer, and vast neovascularization, induced by the angiogenic self-assembling peptide hydrogel (SAPH), SLan. SLan acts as a versatile biocompatible scaffold in the canal space. This study demonstrated a successful collaboration between regenerative medicine and SAPH technology.
Cranial neural crest like cells (CNCLCs) were generated by simplifying a previously established method for deriving neural crest-like cells from iPSCs. The produced CNCLCs showed approximately ∼12,000-fold upregulations of major CNC marker genes. The combination of fibroblast growth factors, FGF4 and FGF9, induced the CNCLCs toward odontoblastic differentiation more effectively than BMP4. In a mice subcutaneous implant model, the CNCLCs replicated the characteristics of dental pulp harboring vast neovascularization with the aid of the angiogenic hydrogel, SLan.
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Siddiqui Z, Acevedo-Jake AM, Griffith A, Kadincesme N, Dabek K, Hindi D, Kim KK, Kobayashi Y, Shimizu E, Kumar V. Cells and material-based strategies for regenerative endodontics. Bioact Mater 2022; 14:234-249. [PMID: 35310358 PMCID: PMC8897646 DOI: 10.1016/j.bioactmat.2021.11.015] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 10/29/2021] [Accepted: 11/09/2021] [Indexed: 12/21/2022] Open
Abstract
The carious process leads to inflammation of pulp tissue. Current care options include root canal treatment or apexification. These procedures, however, result in the loss of tooth vitality, sensitivity, and healing. Pulp capping and dental pulp regeneration are continually evolving techniques to regenerate pulp tissue, avoiding necrosis and loss of vitality. Many studies have successfully employed stem/progenitor cell populations, revascularization approaches, scaffolds or material-based strategies for pulp regeneration. Here we outline advantages and disadvantages of different methods and techniques which are currently being used in the field of regenerative endodontics. We also summarize recent findings on efficacious peptide-based materials which target the dental niche. .
Affiliation(s)
- Zain Siddiqui
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Amanda M. Acevedo-Jake
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Alexandra Griffith
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Nurten Kadincesme
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Kinga Dabek
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Dana Hindi
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Ka Kyung Kim
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
| | - Yoshifumi Kobayashi
- Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ, 07103, USA
| | - Emi Shimizu
- Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ, 07103, USA
- Department of Endodontics, Rutgers School of Dental Medicine, Newark, NJ, 07103, USA
| | - Vivek Kumar
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
- Department of Endodontics, Rutgers School of Dental Medicine, Newark, NJ, 07103, USA
- Department of Chemicals and Materials Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
- Department of Biology, New Jersey Institute of Technology, Newark, NJ, 07102, USA
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Pasiewicz R, Valverde Y, Narayanan R, Kim JH, Irfan M, Lee NS, George A, Cooper LF, Alapati SB, Chung S. C5a complement receptor modulates odontogenic dental pulp stem cell differentiation under hypoxia. Connect Tissue Res 2022; 63:339-348. [PMID: 34030523 PMCID: PMC8611100 DOI: 10.1080/03008207.2021.1924696] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
AIM Alterations in the microenvironment change the phenotypes of dental pulp stem cells (DPSCs). The role of complement component C5a in the differentiation of DPSCs is unknown, especially under oxygen-deprived conditions. The aim of this study was to determine the effect of C5a on the odontogenic differentiation of DPSCs under normoxia and hypoxia. MATERIAL AND METHODS Human DPSCs were subjected to odontogenic differentiation in osteogenic media and treated with the C5a receptor antagonist-W54011 under normal and hypoxic conditions (2% oxygen). Immunochemistry, western blot, and PCR analysis for the various odontogenic differentiation genes/proteins were performed. RESULTS Our results demonstrated that C5a plays a positive role in the odontogenic differentiation of DPSCs. C5a receptor inhibition resulted in a significant decrease in odontogenic differentiation genes, such as DMP1, ON, RUNX2, DSPP compared with the control. This observation was further supported by the Western blot data for DSPP and DMP1 and immunohistochemical analysis. The hypoxic condition reversed this effect. CONCLUSIONS Our results demonstrate that C5a regulates the odontogenic DPSC differentiation under normoxia. Under hypoxia, C5a exerts a reversed function for DPSC differentiation. Taken together, we identified that C5a and oxygen levels are key initial signals during pulp inflammation to control the odontogenic differentiation of DPSCs, thereby, providing a mechanism for potential therapeutic interventions for dentin repair and vital tooth preservation.
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Affiliation(s)
- Ryan Pasiewicz
- Department of Endodontics, University of Illinois at Chicago, Chicago, Illinois 60612, USA
| | - Yessenia Valverde
- Department of Oral Biology, University of Illinois at Chicago, Chicago, Illinois 60612, USA
| | - Raghuvaran Narayanan
- Department of Endodontics, University of Illinois at Chicago, Chicago, Illinois 60612, USA
| | - Ji-Hyun Kim
- Department of Oral Biology, University of Illinois at Chicago, Chicago, Illinois 60612, USA
| | - Muhammad Irfan
- Department of Oral Biology, University of Illinois at Chicago, Chicago, Illinois 60612, USA
| | - Nam-Seob Lee
- Department of Oral Biology, University of Illinois at Chicago, Chicago, Illinois 60612, USA
| | - Anne George
- Department of Oral Biology, University of Illinois at Chicago, Chicago, Illinois 60612, USA
| | - Lyndon F Cooper
- Department of Oral Biology, University of Illinois at Chicago, Chicago, Illinois 60612, USA
| | - Satish B Alapati
- Department of Endodontics, University of Illinois at Chicago, Chicago, Illinois 60612, USA
| | - Seung Chung
- Department of Oral Biology, University of Illinois at Chicago, Chicago, Illinois 60612, USA
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Mosaddad SA, Rasoolzade B, Namanloo RA, Azarpira N, Dortaj H. Stem cells and common biomaterials in dentistry: a review study. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2022; 33:55. [PMID: 35716227 PMCID: PMC9206624 DOI: 10.1007/s10856-022-06676-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 05/16/2022] [Indexed: 05/16/2023]
Abstract
Stem cells exist as normal cells in embryonic and adult tissues. In recent years, scientists have spared efforts to determine the role of stem cells in treating many diseases. Stem cells can self-regenerate and transform into some somatic cells. They would also have a special position in the future in various clinical fields, drug discovery, and other scientific research. Accordingly, the detection of safe and low-cost methods to obtain such cells is one of the main objectives of research. Jaw, face, and mouth tissues are the rich sources of stem cells, which more accessible than other stem cells, so stem cell and tissue engineering treatments in dentistry have received much clinical attention in recent years. This review study examines three essential elements of tissue engineering in dentistry and clinical practice, including stem cells derived from the intra- and extra-oral sources, growth factors, and scaffolds.
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Affiliation(s)
- Seyed Ali Mosaddad
- Student Research Committee, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Boshra Rasoolzade
- Student Research Committee, Department of Pediatric Dentistry, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hengameh Dortaj
- Department of Tissue Engineering, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
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Fu Z, Zhuang Y, Cui J, Sheng R, Tomás H, Rodrigues J, Zhao B, Wang X, Lin K. Development and challenges of cells- and materials-based tooth regeneration. ENGINEERED REGENERATION 2022; 3:163-181. [DOI: 10.1016/j.engreg.2022.04.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
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Long Noncoding RNA IGFBP7-AS1 Promotes Odontogenesis of Stem Cells from Human Exfoliated Deciduous Teeth via the p38 MAPK Pathway. Stem Cells Int 2022; 2022:9227248. [PMID: 35469296 PMCID: PMC9034958 DOI: 10.1155/2022/9227248] [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: 12/16/2021] [Accepted: 03/21/2022] [Indexed: 12/16/2022] Open
Abstract
Stem cells from human exfoliated deciduous teeth (SHED) are attractive seed cells for dental tissue engineering. Epigenetics refers to heritable changes in gene expression patterns that do not alter DNA sequences. Long noncoding RNAs (lncRNAs) are one of the main methods of epigenetic regulation and participate in cell differentiation; however, little is known regarding the role of lncRNAs during SHED odontogenic differentiation. In this study, RNA sequencing (RNA-seq) was used to obtain the expression profile of lncRNAs and mRNAs during the odontogenic differentiation of SHED. The effect of IGFBP7-AS1 on odontogenic differentiation of SHED was assessed by alkaline phosphatase (ALP) staining, alizarin red S (ARS) staining, quantitative reverse transcription PCR (qRT-PCR), Western blot, and in vivo. The level of p38 and p-p38 protein expression was examined by Western blot, and the result was verified by adding the p38 inhibitor, SB203580. The expression profiles of lncRNAs and mRNAs were identified by RNA-seq analysis, which help us to further understand the mechanism in odontogenesis epigenetically. IGFBP7-AS1 expression was increased during odontogenic differentiation on days 7 and 14. The ALP staining, ARS staining, and expression of odontogenic markers were upregulated by overexpressing IGFBP7-AS1 in vitro, whereas the expression of osteogenesis markers was not significantly changed on mRNA level. The effect of IGFBP7-AS1 was also verified in vivo. IGFBP7-AS1 could further positively regulate odontogenic differentiation through the p38 MAPK pathway. This may provide novel targets for dental tissue engineering.
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Wang LH, Gao SZ, Bai XL, Chen ZL, Yang F. An Up-To-Date Overview of Dental Tissue Regeneration Using Dental Origin Mesenchymal Stem Cells: Challenges and Road Ahead. Front Bioeng Biotechnol 2022; 10:855396. [PMID: 35497335 PMCID: PMC9039056 DOI: 10.3389/fbioe.2022.855396] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 03/02/2022] [Indexed: 11/13/2022] Open
Abstract
Stem cells (SCs) research has experienced exponential growth in recent years. SC-based treatments can enhance the lives of people suffering from cardiac ischemia, Alzheimer’s disease, and regenerative drug conditions, like bone or loss of teeth. Numerous kinds of progenitor/SCs have been hypothesized to depend on their potential to regain and/or heal wounded tissue and partly recover organ function. Growing data suggest that SCs (SCs) are concentrated in functions and that particular tissues have more SCs. Dental tissues, in particular, are considered a significant cause of mesenchymal stem cells (MSCs) cells appropriate for tissue regeneration uses. Tissue regeneration and SCs biology have particular attention in dentistry because they may give a novel method for creating clinical material and/or tissue redevelopment. Dental pulp, dental papilla, periodontal ligament, and dental follicle contain mesenchymal SCs. Such SCs, which must be identified and cultivated in specific tissue culture environments, may be used in tissue engineering applications such as tooth tissue, nerve regeneration, and bone redevelopment. A new cause of SCs, induced pluripotent SCs, was successfully made from human somatic cells, enabling the generation of the patient and disease-specific SCs. The dental SC’s (DSCs) multipotency, rapid proliferation rate, and accessibility make it an ideal basis of MSC for tissue redevelopment. This article discusses current advances in tooth SC investigation and its possible application in tissue redevelopment.
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Affiliation(s)
- Lin-Hong Wang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - Si-Zhe Gao
- Department of Stomatology, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xiao-Lei Bai
- Institute of Basic Science and Forensic Medicine, Hangzhou Medical College, Hangzhou, China
| | - Zheng-Lin Chen
- Hangzhou Junhe Regenerative Medicine Research Center, Hangzhou, China
| | - Fan Yang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
- *Correspondence: Fan Yang,
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