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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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杜 志, 廖 婕, 王 冰, 于 素, 李 晓. [Advantages and prospects of cell derived decellularized extracellular matrix as tissue engineering scaffolds]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2024; 38:1291-1298. [PMID: 39542617 PMCID: PMC11563747 DOI: 10.7507/1002-1892.202404114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 10/17/2024] [Indexed: 11/17/2024]
Abstract
OBJECTIVE To review the application of cell derived decellularized extracellular matrix (CDM) in tissue engineering. METHODS The literature related to the application of CDM in tissue engineering was extensively reviewed and analyzed. RESULTS CDM is a mixture of cells and their secretory products obtained by culturing cells in vitro for a period of time, and then the mixture is treated by decellularization. Compared with tissue derived decellularized extracellular matrix (TDM), CDM can screen and utilize pathogen-free autologous cells, effectively avoiding the possible shortcomings of TDM, such as immune response and limited sources. In addition, by selecting the cell source, controlling the culture conditions, and selecting the template scaffold, the composition, structure, and mechanical properties of the scaffold can be controlled to obtain the desired scaffold. CDM retains the components and microstructure of extracellular matrix and has excellent biological functions, so it has become the focus of tissue engineering scaffolds. CONCLUSION CDM is superior in the field of tissue engineering because of its outstanding adjustability, safety, and high bioactivity. With the continuous progress of technology, CDM stents suitable for clinical use are expected to continue to emerge.
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Affiliation(s)
- 志坡 杜
- 保定市第四中心医院骨科（河北保定 072350）Department of Orthopedics, the Fourth Central Hospital of Baoding City, Baoding Hebei, 072350, P. R. China
| | - 婕 廖
- 保定市第四中心医院骨科（河北保定 072350）Department of Orthopedics, the Fourth Central Hospital of Baoding City, Baoding Hebei, 072350, P. R. China
| | - 冰冰 王
- 保定市第四中心医院骨科（河北保定 072350）Department of Orthopedics, the Fourth Central Hospital of Baoding City, Baoding Hebei, 072350, P. R. China
| | - 素香 于
- 保定市第四中心医院骨科（河北保定 072350）Department of Orthopedics, the Fourth Central Hospital of Baoding City, Baoding Hebei, 072350, P. R. China
| | - 晓明 李
- 保定市第四中心医院骨科（河北保定 072350）Department of Orthopedics, the Fourth Central Hospital of Baoding City, Baoding Hebei, 072350, P. R. China
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Yang N, Shen R, Yang W, Zhang S, Gong T, Liu Y. Biomimetic pulp scaffolds prepared from extracellular matrix derived from stem cells from human exfoliated deciduous teeth promote pulp-dentine complex regeneration. Int Endod J 2024; 57:1279-1292. [PMID: 38828966 DOI: 10.1111/iej.14099] [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: 10/17/2023] [Revised: 03/25/2024] [Accepted: 05/08/2024] [Indexed: 06/05/2024]
Abstract
AIM To evaluate the role of biomimetic pulp scaffolds derived from the extracellular matrix derived of stem cells from human exfoliated deciduous teeth (SHED-ECM-PS) in promoting pulp-dentine complex regeneration. METHODOLOGY SHED-ECM-PS was prepared through cell aggregation and decellularization techniques. Histological and immunofluorescence analyses, scanning electron microscopy, and DNA quantification assays were used to characterize the SHED-ECM-PS. Additionally, a tooth slice implantation model was established to evaluate the effects of SHED-ECM-PS on regeneration of the pulp-dentine complex in vivo. Extraction medium for SHED-ECM-PS was prepared, and its effect on bone marrow mesenchymal stem cells (BMMSCs) was assessed in vitro. Cell counting kit-8 and Ki-67 staining assays were performed to determine cell proliferation. The rate of apoptosis was evaluated by flow cytometry. Wound healing and transwell assays were conducted to evaluate cell migration. Alizarin red S staining was performed to examine mineralized nodule formation. Western blotting was used to detect the expression of osteogenic and odontogenic markers. The results were analysed using an independent two-tailed Student's t-test. p < .05 was considered statistically significant. RESULTS SHED-ECM-PS was successfully constructed, exhibiting a striped dental pulp-like shape devoid of nuclear structures or DNA components, and rich in fibronectin, collagen I, DMP1 and DSPP. Notably, SHED-ECM-PS showed no impact on the proliferation or apoptosis of BMMSCs. Histological analysis revealed that dental pulp fibroblasts formed an interwoven mesh in the root canal, and angiogenesis was observed in the SHED-ECM-PS group. Moreover, a continuous, newly formed tubular dentine layer with polarized odontoblast-like cells was observed along the inner wall of the root canal. SHED-ECM-PS promoted the migration, polar alignment and mineralized nodule formation of BMMSCs and specifically elevated the expression levels of odontogenic markers, but not osteogenic markers, compared with the control group in vitro. CONCLUSION SHED-ECM-PS exhibited no cytotoxicity and promoted pulp-dentine complex regeneration in vivo as well as cell migration and odontogenic differentiation of BMMSCs in vitro. These findings provide evidence that SHED-ECM-PS, as a novel biological scaffold, has the potential to improve the outcomes of REPs.
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Affiliation(s)
- Ning Yang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, China
- Liaoning Province Key Laboratory of Oral Disease, Shenyang, China
| | - Rou Shen
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, China
- Liaoning Province Key Laboratory of Oral Disease, Shenyang, China
| | - Wenxiao Yang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, China
- Liaoning Province Key Laboratory of Oral Disease, Shenyang, China
| | - Shengcai Zhang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, China
- Liaoning Province Key Laboratory of Oral Disease, Shenyang, China
| | - Tianxing Gong
- Department of Biomedical Engineering, Shenyang University of Technology, Shenyang, China
| | - Yao Liu
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, China
- Liaoning Province Key Laboratory of Oral Disease, Shenyang, China
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Koutrouli A, Machla F, Arapostathis K, Kokoti M, Bakopoulou A. "Biological responses of two calcium-silicate-based cements on a tissue-engineered 3D organotypic deciduous pulp analogue". Dent Mater 2024; 40:e14-e25. [PMID: 38431482 DOI: 10.1016/j.dental.2024.02.024] [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: 09/25/2023] [Revised: 02/14/2024] [Accepted: 02/18/2024] [Indexed: 03/05/2024]
Abstract
OBJECTIVES The biological responses of MTA and Biodentine™ has been assessed on a three-dimensional, tissue-engineered organotypic deciduous pulp analogue. METHODS Human endothelial (HUVEC) and dental mesenchymal stem cells (SHED) at a ratio of 3:1, were incorporated into a collagen I/fibrin hydrogel; succeeding Biodentine™ and MTA cylindrical specimens were placed in direct contact with the pulp analogue 48 h later. Cell viability/proliferation and morphology were evaluated through live/dead staining, MTT assay and Scanning Electron Microscopy (SEM), and expression of angiogenic, odontogenic markers through real time PCR. RESULTS Viable cells dominated at day 3 after treatment presenting typical morphology, firmly attached within the hydrogel structures, as shown by live/dead staining and SEM images. MTT assay at day 1 presented a significant increase of cell proliferation in Biodentine™ group. Real-time PCR showed significant upregulation of odontogenic markers DSPP, BMP-2 (day 3,6), RUNX2, ALP (day 3) in contact with Biodentine™ compared to MTA and the control, whereas MTA promoted significant upregulation of DSPP, BMP-2, RUNX2, Osterix (day 3) and ALP (day 6) compared to the control. MSX1 presented downregulation in both experimental groups. Expression of angiogenic markers VEGFa and ANGPT-1 at day 3 was significantly upregulated in contact with Biodentine™ and MTA respectively, while the receptors VEGFR1, VEGFR2 and Tie-2, as well as PECAM-1 were downregulated. SIGNIFICANCE Both calcium silicate-based materials are biocompatible and exert positive angiogenic and odontogenic effects, although Biodentine™ during the first days of culture, seems to induce higher cell proliferation and provoke a more profound odontogenic and angiogenic response from SHED.
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Affiliation(s)
- A Koutrouli
- Department of Paediatric Dentistry, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece
| | - F Machla
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece
| | - K Arapostathis
- Department of Paediatric Dentistry, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece
| | - M Kokoti
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece
| | - A Bakopoulou
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece.
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Luo C, He J, Wang N, Zhu N, Zhang L, Wang Y, Qin M, Hui T. Enhanced reparatory effect of EI1 on dental pulp via extracellular matrix remodeling by miR-181b-2-3p inhibitor. J Dent Sci 2024; 19:177-185. [PMID: 38303812 PMCID: PMC10829547 DOI: 10.1016/j.jds.2023.05.002] [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: 03/29/2023] [Revised: 05/02/2023] [Indexed: 02/03/2024] Open
Abstract
Background/purpose Extracellular matrix (ECM) is crucial for dental pulp repair. The aim of this paper is to investigate the ECM remodeling effect of miR-181b-2-3p (a microRNA) and to verify the reparatory effect of EI1 (an epigenetic drug) and miR-181b-2-3p inhibitor on dental pulp. Materials and methods Levels of ECM-related factors in EI1-treated human dental pulp cells (hDPCs) were measured by qRT-PCR and Western blot. The anti-inflammation effect of EI1 was examined in Lipopolysaccharide-stimulated hDPCs. miR-181b-2-3p mimics or inhibitors were transfected into hDPCs and then the cells' functions were detected. A dual luciferase reporter assay was used to identify the targets of miR-181b-2-3p. Pulpotomy using miR-181b-2-3p antagomirs and EI1 as pulp capping materials was performed in male six-week-old Sprague-Dawley rats. Results EI1 upregulated ECM-related genes expression in hDPCs, but failed to upregulate the collagen1A1 (COL1A1) protein level. Pro-inflammatory factors were downregulated by EI1 in Lipopolysaccharide-stimulated hDPCs. Overexpression of miR-181b-2-3p downregulated the expression of transforming growth factor-β2 (TGF-β2) and fibronectin type III domain-containing protein 5 precursor (FNDC5), while the inhibition had the opposite effect. Dual luciferase reporter assays demonstrated that miR-181b-2-3p targets TGF-β2, FNDC5 and integrin alpha 4 protein (ITGA4). Compared to EI1 was used alone, EI1 combined with the inhibitor upregulated the protein levels of COL1A1, fibronectin (FN1) and TGF-β2 in hDPCs, promoted hDPCs migration, and exhibited reparatory effects on inflamed rat pulp tissue. Conclusion miR-181b-2-3p inhibitor could enhance the reparatory effect of EI1 via ECM remodeling in dental pulp both in vitro and in vivo.
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Affiliation(s)
- Chiyi Luo
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
| | - Jie He
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
- Shenzhen Children's Hospital, Shenzhen, China
| | - Nan Wang
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
| | - Ningxin Zhu
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
| | - Lixin Zhang
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
| | - Yuanyuan Wang
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
| | - Man Qin
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
| | - Tianqian Hui
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
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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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Li X, Wang Y, Huang D, Jiang Z, He Z, Luo M, Lei J, Xiao Y. Nanomaterials Modulating the Fate of Dental-Derived Mesenchymal Stem Cells Involved in Oral Tissue Reconstruction: A Systematic Review. Int J Nanomedicine 2023; 18:5377-5406. [PMID: 37753067 PMCID: PMC10519211 DOI: 10.2147/ijn.s418675] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 09/03/2023] [Indexed: 09/28/2023] Open
Abstract
The critical challenges in repairing oral soft and hard tissue defects are infection control and the recovery of functions. Compared to conventional tissue regeneration methods, nano-bioactive materials have become the optimal materials with excellent physicochemical properties and biocompatibility. Dental-derived mesenchymal stem cells (DMSCs) are a particular type of mesenchymal stromal cells (MSCs) with great potential in tissue regeneration and differentiation. This paper presents a review of the application of various nano-bioactive materials for the induction of differentiation of DMSCs in oral and maxillofacial restorations in recent years, outlining the characteristics of DMSCs, detailing the biological regulatory effects of various nano-materials on stem cells and summarizing the material-induced differentiation of DMSCs into multiple types of tissue-induced regeneration strategies. Nanomaterials are different and complementary to each other. These studies are helpful for the development of new nanoscientific research technology and the clinical transformation of tissue reconstruction technology and provide a theoretical basis for the application of nanomaterial-modified dental implants. We extensively searched for papers related to tissue engineering bioactive constructs based on MSCs and nanomaterials in the databases of PubMed, Medline, and Google Scholar, using keywords such as "mesenchymal stem cells", "nanotechnology", "biomaterials", "dentistry" and "tissue regeneration". From 2013 to 2023, we selected approximately 150 articles that align with our philosophy.
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Affiliation(s)
- Xingrui Li
- Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, the Affiliated Stomatological Hospital of Southwest Medical University, Institute of Stomatology, Southwest Medical University, Luzhou, People’s Republic of China
| | - Yue Wang
- Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, the Affiliated Stomatological Hospital of Southwest Medical University, Institute of Stomatology, Southwest Medical University, Luzhou, People’s Republic of China
| | - Denghao Huang
- Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, the Affiliated Stomatological Hospital of Southwest Medical University, Institute of Stomatology, Southwest Medical University, Luzhou, People’s Republic of China
| | - Zhonghao Jiang
- Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, the Affiliated Stomatological Hospital of Southwest Medical University, Institute of Stomatology, Southwest Medical University, Luzhou, People’s Republic of China
| | - Zhiyu He
- Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, the Affiliated Stomatological Hospital of Southwest Medical University, Institute of Stomatology, Southwest Medical University, Luzhou, People’s Republic of China
| | - Maoxuan Luo
- Department of Orthodontics, the Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, People’s Republic of China
| | - Jie Lei
- Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, the Affiliated Stomatological Hospital of Southwest Medical University, Institute of Stomatology, Southwest Medical University, Luzhou, People’s Republic of China
- Department of Orthodontics, the Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, People’s Republic of China
| | - Yao Xiao
- Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, the Affiliated Stomatological Hospital of Southwest Medical University, Institute of Stomatology, Southwest Medical University, Luzhou, People’s Republic of China
- Department of Orthodontics, the Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, People’s Republic of China
- Department of Chengbei Outpatient, the Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, People’s Republic of China
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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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Hong H, Zeng K, Zhou C, Chen X, Xu Z, Li M, Liu L, Zeng Q, Tao Q, Wei X. The pluripotent factor OCT4A enhances the self-renewal of human dental pulp stem cells by targeting lncRNA FTX in an LPS-induced inflammatory microenvironment. Stem Cell Res Ther 2023; 14:109. [PMID: 37106382 PMCID: PMC10142416 DOI: 10.1186/s13287-023-03313-8] [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: 04/03/2022] [Accepted: 03/29/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND Regulating the pluripotency of human dental pulp stem cells (hDPSCs) is key for the self-repair of injured dental pulp. We previously found that OCT4A promotes the proliferation and odontogenic differentiation of human dental pulp cells (hDPCs). Recent studies have shown the interaction between OCT4A and lncRNAs in pluripotency maintenance of various stem cells. The aim of this study was to explore the underlying roles and mechanisms of OCT4A and its related lncRNAs in the proliferation and multidirectional differentiation of hDPSCs in an inflammatory microenvironment. METHODS Human lncRNA microarrays were applied to screen out the differentially expressed lncRNAs in hDPSCs between the OCT4A-overexpressing and vector groups. Lipopolysaccharide (LPS) was used to simulate the inflammatory microenvironment. The effects of OCT4A and the lncRNA FTX on the proliferation and multidifferentiation of hDPSCs were observed by the CCK-8 assay, EdU staining, real-time PCR, western blotting, and Alizarin red and oil red O staining. Bioinformatics analysis and chromatin immunoprecipitation (ChIP) assays were performed to clarify the targeted mechanism of OCT4A on FTX. The regulation by FTX of the expression of OCT4A and its downstream pluripotent transcription factors SOX2 and c-MYC was further detected by real-time PCR and western blotting. RESULTS The microarray results showed that 978 lncRNAs (250 of which were upregulated and 728 downregulated) were potentially differentially expressed genes (fold change ≥ 2, P < 0.05). LPS stimulation attenuated the self-renewal of hDPSCs. OCT4A enhanced the cell proliferation and multidifferentiation capacities of hDPSCs in an inflammatory microenvironment, while FTX exhibited the opposite effects. OCT4A negatively regulated FTX function by binding to specific regions on the FTX promoter, thereby inhibiting the transcription of FTX. Moreover, overexpression of FTX downregulated the expression of OCT4A, SOX2 and c-MYC, whereas knockdown of FTX facilitated their expression. CONCLUSIONS OCT4A was found to be a crucial factor maintaining the self-renewal of hDPSCs by transcriptionally targeting FTX in an inflammatory microenvironment. Moreover, we proposed a novel function of FTX in negatively regulating the pluripotency and multilineage differentiation capacity of hDPSCs. The hierarchical organization between OCT4A and FTX expanded the understanding of the network between transcription factors and lncRNAs in fine-tuning the pluripotency/differentiation balance of adult stem cells, and provided prospective targets for optimizing dental-derived stem cell sources for regenerative endodontics.
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Affiliation(s)
- Hong Hong
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, 510055, People's Republic of China
| | - Kai Zeng
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, 510055, People's Republic of China
| | - Can Zhou
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, 510055, People's Republic of China
| | - Xiaochuan Chen
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, 510055, People's Republic of China
| | - Zhezhen Xu
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, 510055, People's Republic of China
| | - Mengjie Li
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, 510055, People's Republic of China
| | - Lu Liu
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, 510055, People's Republic of China
| | - Qian Zeng
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, 510055, People's Republic of China
| | - Qian Tao
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, 510055, People's Republic of China.
| | - Xi Wei
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, 510055, People's Republic of China.
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Differential Effects of Extracellular Matrix Glycoproteins Fibronectin and Laminin-5 on Dental Pulp Stem Cell Phenotypes and Responsiveness. J Funct Biomater 2023; 14:jfb14020091. [PMID: 36826890 PMCID: PMC9963712 DOI: 10.3390/jfb14020091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 01/31/2023] [Accepted: 02/03/2023] [Indexed: 02/11/2023] Open
Abstract
Dental pulp stem cells (DPSCs) are mesenchymal stem cells (MSCs) with the potential to differentiate in a limited number of other tissue types. Some evidence has suggested the modulation of DPSC growth may be mediated, in part, by exogenous extracellular matrix (ECM) glycoproteins, including fibronectin (FN) and laminin-5 (LN5). Although preliminary research suggests that some ECM glycoproteins may work as functional biomaterials to modulate DPSC growth responses, the primary goal of this project is to determine the specific effects of FN and LN5 on DPSC growth and viability. Using an existing DPSC repository, n = 16 DPSC isolates were cultured and 96-well growth assays were performed, which revealed FN, LN5 and the combination of these were sufficient to induce statistically significant changes in growth among five (n = 5) DPSC isolates. In addition, the administration of FN (either alone or in combination) was sufficient to induce the expression of alkaline phosphatase (ALP) and dentin sialophosphoprotein (DSPP), while LN5 induced the expression of ALP only, suggesting differential responsiveness among DPSCs. Moreover, these responses appeared to correlate with the expression of MSC biomarkers NANOG, Oct4 and Sox2. These results add to the growing body of evidence suggesting that functional biomaterials, such as ECM glycoproteins FN and LN5, are sufficient to induce phenotypic and differentiation-specific effects in a specific subset of DPSC isolates. More research will be needed to determine which biomarkers or additional factors are necessary and sufficient to induce the differentiation and development of DPSCs ex vivo and in vitro for biomedical applications.
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11
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Effect of chitosan irrigant solutions on the release of bioactive proteins from root dentin. Clin Oral Investig 2023; 27:691-703. [PMID: 36401068 DOI: 10.1007/s00784-022-04787-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 11/10/2022] [Indexed: 11/19/2022]
Abstract
OBJECTIVE To identify the effect of two chitosan solutions on the release of root dentin matrix proteins and to describe the chemical changes observed following conditioning with chelating agents. MATERIALS AND METHODS The release of dentin sialoprotein (DSP), transforming growth factor-beta 1 (TGF-β1), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-BB (PDGF-BB) with different chelating agents, including ethylenediaminetetraacetic acid (EDTA), chitosan solution (CS), and nanoparticulate chitosan (CSnp), was investigated. DSP was quantified using an enzyme-linked immunosorbent assay (ELISA). TGF-β1, VEGF, and PDGF-BB were quantified using a cytokine bead panel (CBA). Raman spectroscopy was performed to identify surface chemical changes. Statistical analysis was performed using Kruskal-Wallis test with Mann-Whitney-Wilcoxon rank-sum test (p < 0.05). RESULTS TGF-β1, VEGF, and DSP solubilized in all irrigants tested. CSnp showed the highest concentration of DSP. PDGF-BB did not exceed the detection limits. Raman spectroscopy revealed a decrease in the phosphate and carbonate peaks, representing the chelating effect of EDTA, CS, and CSnp. Additionally, CSnp showed the greatest preservation of the amide I and III content. CONCLUSION Proteins can be released from dentin via EDTA, CS, and CSnp conditioning. Raman spectroscopic revealed changes in the inorganic content of the root dentin after chelation. Furthermore, use of CSnp facilitated a preservation of the organic content. CLINICAL RELEVANCE Chelation allows the release of proteins, justifying the use of chelating agents in regenerative endodontics. The chitosan-dentin matrix interaction also promotes the protection of the organic content as an additional benefit to its protein releasing effect.
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12
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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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13
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Kumar N, Maher N, Amin F, Ghabbani H, Zafar MS, Rodríguez-Lozano FJ, Oñate-Sánchez RE. Biomimetic Approaches in Clinical Endodontics. Biomimetics (Basel) 2022; 7:biomimetics7040229. [PMID: 36546929 PMCID: PMC9775094 DOI: 10.3390/biomimetics7040229] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/19/2022] [Accepted: 12/02/2022] [Indexed: 12/13/2022] Open
Abstract
In the last few decades, biomimetic concepts have been widely adopted in various biomedical fields, including clinical dentistry. Endodontics is an important sub-branch of dentistry which deals with the different conditions of pulp to prevent tooth loss. Traditionally, common procedures, namely pulp capping, root canal treatment, apexification, and apexigonesis, have been considered for the treatment of different pulp conditions using selected materials. However, clinically to regenerate dental pulp, tissue engineering has been advocated as a feasible approach. Currently, new trends are emerging in terms of regenerative endodontics which have led to the replacement of diseased and non-vital teeth into the functional and healthy dentine-pulp complex. Root- canal therapy is the standard management option when dental pulp is damaged irreversibly. This treatment modality involves soft-tissue removal and then filling that gap through the obturation technique with a synthetic material. The formation of tubular dentine and pulp-like tissue formation occurs when stem cells are transplanted into the root canal with an appropriate scaffold material. To sum up tissue engineering approach includes three components: (1) scaffold, (2) differentiation, growth, and factors, and (3) the recruitment of stem cells within the pulp or from the periapical region. The aim of this paper is to thoroughly review and discuss various pulp-regenerative approaches and materials used in regenerative endodontics which may highlight the current trends and future research prospects in this particular area.
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Affiliation(s)
- Naresh Kumar
- Department of Science of Dental Materials, Dr. Ishrat Ul Ebad Khan Institute of Oral Health Sciences, Dow University of Health Sciences, Karachi 74200, Pakistan
- Correspondence: ; Tel.: +92-333-2818500
| | - Nazrah Maher
- Department of Science of Dental Materials, Dr. Ishrat Ul Ebad Khan Institute of Oral Health Sciences, Dow University of Health Sciences, Karachi 74200, Pakistan
| | - Faiza Amin
- Department of Science of Dental Materials, Dow Dental College, Dow University of Health Sciences, Karachi 74200, Pakistan
| | - Hani Ghabbani
- Department of Restorative Dentistry, College of Dentistry, Taibah University, Al Madinah, Al Munawwarah 41311, Saudi Arabia
| | - Muhammad Sohail Zafar
- Department of Restorative Dentistry, College of Dentistry, Taibah University, Al Madinah, Al Munawwarah 41311, Saudi Arabia
- Department of Dental Materials, Islamic International Dental College, Riphah International University, Islamabad 44000, Pakistan
| | | | - Ricardo E. Oñate-Sánchez
- Department of Special Care in Dentistry, Hospital Morales Meseguer, IMIB-Arrixaca, University of Murcia, 30008 Murcia, Spain
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14
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Zhou J, Ou MH, Wei XL, Lan BY, Chen WJ, Song SJ, Chen WX. The role of different macrophages-derived conditioned media in dental pulp tissue regeneration. Tissue Cell 2022; 79:101944. [DOI: 10.1016/j.tice.2022.101944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 09/21/2022] [Accepted: 09/21/2022] [Indexed: 10/14/2022]
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15
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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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Phothichailert S, Nowwarote N, Fournier BP, Trachoo V, Roytrakul S, Namangkalakul W, Osathanon T. Effects of decellularized extracellular matrix derived from Jagged1-treated human dental pulp stem cells on biological responses of stem cells isolated from apical papilla. Front Cell Dev Biol 2022; 10:948812. [PMID: 36081912 PMCID: PMC9445441 DOI: 10.3389/fcell.2022.948812] [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: 05/20/2022] [Accepted: 07/21/2022] [Indexed: 11/30/2022] Open
Abstract
Objective: Indirect Jagged1 immobilization efficiently activates canonical Notch signaling in human dental pulp stem cells (hDPSCs). This study aimed to investigate the characteristics of the Jagged1-treated hDPSC-derived decellularized extracellular matrix (dECM) and its biological activity on odonto/osteogenic differentiation of stem cells isolated from apical papilla (SCAPs). Methods: Bioinformatic database of Jagged1-treated hDPSCs was analyzed using NetworkAnalyst. hDPSCs seeded on the Jagged1 immobilized surface were maintained with normal or osteogenic induction medium (OM) followed by decellularization procedure, dECM-N, or dECM-OM, respectively. SCAPs were reseeded on each dECM with either the normal medium or the OM. Cell viability was determined by MTT assay. Characteristics of dECMs and SCAPs were evaluated by SEM, EDX, immunofluorescent staining, and alcian blue staining. Mineralization was assessed by alizarin red S, Von Kossa, and alkaline phosphatase staining. Statistical significance was considered at p < 0.05. Results: RNA-seq database revealed upregulation of several genes involved in ECM organization, ECM–receptor interaction, and focal adhesion in Jagged1-treated hDPSCs. Immobilized Jagged1 increased the osteogenesis of the hDPSC culture with OM. dECMs showed fibrillar-like network structure and maintained major ECM proteins, fibronectin, type I-collagen, and glycosaminoglycans. A decrease in calcium and phosphate components was observed in dECMs after the decellularized process. Cell viability on dECMs did not alter by 7 days. Cell attachment and f-actin cytoskeletal organization of SCAPs proliferated on Jagged1-treated dECMs were comparable to those of the control dECMs. SCAPs exhibited significantly higher mineralization on dECM-N in OM and markedly enhanced on dECM-OM with normal medium or OM conditions. Conclusion: Jagged1-treated hDPSC-derived dECMs are biocompatible and increase odonto/osteogenic differentiation of SCAPs. The results suggested the potential of Jagged1 dECMs, which could be further developed into ECM scaffolds for application in regenerative medicine.
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Affiliation(s)
- Suphalak Phothichailert
- Dental Stem Cell Biology Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Nunthawan Nowwarote
- Universite Paris Cite, Faculty of Dentistry, Department of Oral Biology, Paris, France
- Centre de Recherche des Cordeliers, Sorbonne Universite, INSERM UMRS, Molecular Oral Pathophysiology, Paris, France
| | - Benjamin P.J. Fournier
- Universite Paris Cite, Faculty of Dentistry, Department of Oral Biology, Paris, France
- Centre de Recherche des Cordeliers, Sorbonne Universite, INSERM UMRS, Molecular Oral Pathophysiology, Paris, France
| | - Vorapat Trachoo
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Sittiruk Roytrakul
- Proteomics Research Laboratory, Genome Institute, National Center of Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand
| | - Worachat Namangkalakul
- Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
- *Correspondence: Worachat Namangkalakul,
| | - Thanaphum Osathanon
- Dental Stem Cell Biology Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
- Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
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17
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Zeng A, Li H, Liu J, Wu M. The Progress of Decellularized Scaffold in Stomatology. Tissue Eng Regen Med 2022; 19:451-461. [PMID: 35320505 PMCID: PMC9130370 DOI: 10.1007/s13770-022-00432-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 12/26/2021] [Accepted: 01/05/2022] [Indexed: 10/18/2022] Open
Abstract
The oral and maxillofacial region contains oral organs and facial soft tissues. Due to the complexity of the structures and functions of this region, the repair of related defects is complicated. Different degrees of defects require different repair methods, which involve a great combination of medicine and art, and the material requirements are extremely high. Hence, clinicians are plagued by contemporary oral repair materials due to the limitations of bone harvesting, immune rejection, low osteogenic activity and other problems. Decellularized extracellular matrix has attracted much attention as a bioactive scaffold material because of its nonimmunogenic properties, good osteogenic properties, slow release of growth factors, promotion of seed cell adhesion and maintenance of stem cell characteristics. This article reviews the sources, preparation methods, application and research progress of extracellular matrix materials in the repair of oral and maxillofacial defects to provide an overview for fundamental research and clinical development.
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Affiliation(s)
- Ailin Zeng
- School of Stomatology, Zunyi Medical University, No. 6 West Xuefu Road, Xinpu District, Zunyi, 563006, Guizhou, China
| | - Huiru Li
- School of Stomatology, Zunyi Medical University, No. 6 West Xuefu Road, Xinpu District, Zunyi, 563006, Guizhou, China
| | - Jianguo Liu
- School of Stomatology, Zunyi Medical University, No. 6 West Xuefu Road, Xinpu District, Zunyi, 563006, Guizhou, China.
- Special Key Laboratory of Oral Disease Research of Higher Education Institution of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou, China.
| | - Mingsong Wu
- School of Stomatology, Zunyi Medical University, No. 6 West Xuefu Road, Xinpu District, Zunyi, 563006, Guizhou, China.
- Special Key Laboratory of Oral Disease Research of Higher Education Institution of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou, China.
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18
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Ning LJ, Cui J, He SK, Hu RN, Yao X, Zhang Y, Ding W, Zhang YJ, Luo JC, Qin TW. Constructing a highly bioactive tendon-regenerative scaffold by surface modification of tissue-specific stem cell derived extracellular matrix. Regen Biomater 2022; 9:rbac020. [PMID: 35480863 PMCID: PMC9036902 DOI: 10.1093/rb/rbac020] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 01/28/2022] [Accepted: 03/06/2022] [Indexed: 02/05/2023] Open
Abstract
Developing highly bioactive scaffold materials to promote stem cell migration, proliferation and tissue-specific differentiation is a crucial requirement in current tissue engineering and regenerative medicine. Our previous work has demonstrated that the decellularized tendon slices (DTSs) are able to promote stem cell proliferation and tenogenic differentiation in vitro and show certain pro-regenerative capacity for rotator cuff tendon regeneration in vivo. In this study, we present a strategy to further improve the bioactivity of the DTSs for constructing a novel highly bioactive tendon-regenerative scaffold by surface modification of tendon-specific stem cell-derived extracellular matrix (tECM), which is expected to greatly enhance the capacity of scaffold material in regulating stem cell behavior, including migration, proliferation and tenogenic differentiation. We prove that the modification of tECM could change the highly aligned surface topographical cues of the DTSs, retain the surface stiffness of the DTSs and significantly increase the content of multiple ECM components in the tECM-DTSs. As a result, the tECM-DTSs dramatically enhance the migration, proliferation as well as tenogenic differentiation of rat bone marrow-derived stem cells compared with the DTSs. Collectively, this strategy would provide a new way for constructing ECM-based biomaterials with enhanced bioactivity for in situ tendon regeneration applications. ![]()
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Affiliation(s)
- Liang-Ju Ning
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
| | - Jing Cui
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
| | - Shu-Kun He
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
- Department of Orthopedic Surgery, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China
| | - Ruo-Nan Hu
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
| | - Xuan Yao
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
| | - Yi Zhang
- Core Facility, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China
| | - Wei Ding
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
| | - Yan-Jing Zhang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
- Core Facility, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China
| | - Jing-Cong Luo
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
| | - Ting-Wu Qin
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
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19
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Kwack KH, Lee HW. Clinical Potential of Dental Pulp Stem Cells in Pulp Regeneration: Current Endodontic Progress and Future Perspectives. Front Cell Dev Biol 2022; 10:857066. [PMID: 35478967 PMCID: PMC9035692 DOI: 10.3389/fcell.2022.857066] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 03/18/2022] [Indexed: 12/12/2022] Open
Abstract
Dental caries is a common disease that not only destroys the rigid structure of the teeth but also causes pulp necrosis in severe cases. Once pulp necrosis has occurred, the most common treatment is to remove the damaged pulp tissue, leading to a loss of tooth vitality and increased tooth fragility. Dental pulp stem cells (DPSCs) isolated from pulp tissue exhibit mesenchymal stem cell-like characteristics and are considered ideal candidates for regenerating damaged dental pulp tissue owing to their multipotency, high proliferation rate, and viability after cryopreservation. Importantly, DPSCs do not elicit an allogeneic immune response because they are non-immunogenic and exhibit potent immunosuppressive properties. Here, we provide an up-to-date review of the clinical applicability and potential of DPSCs, as well as emerging trends in the regeneration of damaged pulp tissue. In addition, we suggest the possibility of using DPSCs as a resource for allogeneic transplantation and provide a perspective for their clinical application in pulp regeneration.
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Affiliation(s)
- Kyu Hwan Kwack
- Department of Dentistry, Graduate School, Kyung Hee University, Seoul, South Korea
| | - Hyeon-Woo Lee
- Department of Pharmacology, School of Dentistry, Graduate School, Institute of Oral Biology, Kyung Hee University, Seoul, South Korea
- *Correspondence: Hyeon-Woo Lee,
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20
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Nowwarote N, Petit S, Ferre FC, Dingli F, Laigle V, Loew D, Osathanon T, Fournier BPJ. Extracellular Matrix Derived From Dental Pulp Stem Cells Promotes Mineralization. Front Bioeng Biotechnol 2022; 9:740712. [PMID: 35155398 PMCID: PMC8829122 DOI: 10.3389/fbioe.2021.740712] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 12/23/2021] [Indexed: 12/14/2022] Open
Abstract
Background: Extracellular matrix (ECM) plays a pivotal role in many physiological processes. ECM macromolecules and associated factors differ according to tissues, impact cell differentiation, and tissue homeostasis. Dental pulp ECM may differ from other oral tissues and impact mineralization. Thus, the present study aimed to identify the matrisome of ECM proteins derived from human dental pulp stem cells (DPSCs) and its ability to regulate mineralization even in cells which do not respond to assaults by mineralization, the human gingival fibroblasts (GF). Methods: ECM were extracted from DPSCs cultured in normal growth medium supplemented with L-ascorbic acid (N-ECM) or in osteogenic induction medium (OM-ECM). ECM decellularization (dECM) was performed using 0.5% triton X-100 in 20 mM ammonium hydroxide after 21 days. Mass spectrometry and proteomic analysis identified and quantified matrisome proteins. Results: The dECM contained ECM proteins but lacked cellular components and mineralization. Interestingly, collagens (COL6A1, COL6A2, and COL6A3) and elastic fibers (FBN1, FBLN2, FN1, and HSPG2) were significantly represented in N-ECM, while annexins (ANXA1, ANXA4, ANXA5, ANXA6, ANXA7, and ANXA11) were significantly overdetected in OM-ECM. GF were reseeded on N-dECM and OM-dECM and cultured in normal or osteogenic medium. GF were able to attach and proliferate on N-dECM and OM-dECM. Both dECM enhanced mineralization of GF at day 14 compared to tissue culture plate (TCP). In addition, OM-dECM promoted higher mineralization of GF than N-dECM although cultured in growth medium. Conclusions: ECM derived from DPSCs proved to be osteoinductive, and this knowledge supported cell-derived ECM can be further utilized for tissue engineering of mineralized tissues.
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Affiliation(s)
- Nunthawan Nowwarote
- Dental Stem Cell Biology Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
- Centre de Recherche des Cordeliers, INSERM UMRS 1138, Molecular Oral Pathophysiology, Université de Paris, Sorbonne Université, Paris, France
- Department of Oral Biology, Dental Faculty Garancière, Université de Paris, Paris, France
| | - Stephane Petit
- Centre de Recherche des Cordeliers, INSERM UMRS 1138, Molecular Oral Pathophysiology, Université de Paris, Sorbonne Université, Paris, France
| | - Francois Come Ferre
- Centre de Recherche des Cordeliers, INSERM UMRS 1138, Molecular Oral Pathophysiology, Université de Paris, Sorbonne Université, Paris, France
| | - Florent Dingli
- Institut Curie, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique, PSL Research University, Paris, France
| | - Victor Laigle
- Institut Curie, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique, PSL Research University, Paris, France
| | - Damarys Loew
- Institut Curie, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique, PSL Research University, Paris, France
| | - Thanaphum Osathanon
- Dental Stem Cell Biology Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
- Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
- *Correspondence: Thanaphum Osathanon, ; Benjamin P. J. Fournier,
| | - Benjamin P. J. Fournier
- Centre de Recherche des Cordeliers, INSERM UMRS 1138, Molecular Oral Pathophysiology, Université de Paris, Sorbonne Université, Paris, France
- Department of Oral Biology, Dental Faculty Garancière, Université de Paris, Paris, France
- *Correspondence: Thanaphum Osathanon, ; Benjamin P. J. Fournier,
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21
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Khurshid Z, Alnaim AJA, Alhashim AAA, Imran E, Adanir N. Future of Decellularized Dental Pulp Matrix in Regenerative Endodontics. Eur J Dent 2022; 16:737-741. [PMID: 34991166 DOI: 10.1055/s-0041-1741012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
With the advancements in tissue engineering, the repair and regeneration of oral/dental tissue are becoming possible and productive. Due to periodontal diseases, the tooth loses bone support resulting in tooth loss, but bone grafting stabilizes with new bone. It is seen that due to the progression of dental caries, pulp damage happens, and the vitality of the tooth is compromised. The current theme of dental pulp regeneration through biological and synthetic scaffolds, is becoming a potential therapy for pulp revitalization.
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Affiliation(s)
- Zohaib Khurshid
- Department of Prosthodontics and Dental Implantology, College of Dentistry, King Faisal University, Al-Ahsa, Kingdom of Saudi Arabia
| | | | | | - Eisha Imran
- Department of Dental Materials, HITEC Dental College, Institute of Medical Sciences, Taxilla, Pakistan
| | - Necdet Adanir
- Department of Restorative Dentistry, College of Dentistry, King Faisal University, Al-Ahsa, Kingdom of Saudi Arabia
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22
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Yuan X, Yuan Z, Wang Y, Wan Z, Wang X, Yu S, Han J, Huang J, Xiong C, Ge L, Cai Q, Zhao Y. Vascularized pulp regeneration via injecting simvastatin functionalized GelMA cryogel microspheres loaded with stem cells from human exfoliated deciduous teeth. Mater Today Bio 2022; 13:100209. [PMID: 35198958 PMCID: PMC8841886 DOI: 10.1016/j.mtbio.2022.100209] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/20/2022] [Accepted: 01/27/2022] [Indexed: 12/20/2022] Open
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23
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Okić-Đorđević I, Obradović H, Kukolj T, Petrović A, Mojsilović S, Bugarski D, Jauković A. Dental mesenchymal stromal/stem cells in different microenvironments— implications in regenerative therapy. World J Stem Cells 2021; 13:1863-1880. [PMID: 35069987 PMCID: PMC8727232 DOI: 10.4252/wjsc.v13.i12.1863] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/15/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Current research data reveal microenvironment as a significant modifier of physical functions, pathologic changes, as well as the therapeutic effects of stem cells. When comparing regeneration potential of various stem cell types used for cytotherapy and tissue engineering, mesenchymal stem cells (MSCs) are currently the most attractive cell source for bone and tooth regeneration due to their differentiation and immunomodulatory potential and lack of ethical issues associated with their use. The microenvironment of donors and recipients selected in cytotherapy plays a crucial role in regenerative potential of transplanted MSCs, indicating interactions of cells with their microenvironment indispensable in MSC-mediated bone and dental regeneration. Since a variety of MSC populations have been procured from different parts of the tooth and tooth-supporting tissues, MSCs of dental origin and their achievements in capacity to reconstitute various dental tissues have gained attention of many research groups over the years. This review discusses recent advances in comparative analyses of dental MSC regeneration potential with regards to their tissue origin and specific microenvironmental conditions, giving additional insight into the current clinical application of these cells.
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Affiliation(s)
- Ivana Okić-Đorđević
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Hristina Obradović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Tamara Kukolj
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Anđelija Petrović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Slavko Mojsilović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Diana Bugarski
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Aleksandra Jauković
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
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24
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Bhandi S, Alkahtani A, Mashyakhy M, Abumelha AS, Albar NHM, Renugalakshmi A, Alkahtany MF, Robaian A, Almeslet AS, Patil VR, Varadarajan S, Balaji TM, Reda R, Testarelli L, Patil S. Effect of Ascorbic Acid on Differentiation, Secretome and Stemness of Stem Cells from Human Exfoliated Deciduous Tooth (SHEDs). J Pers Med 2021; 11:jpm11070589. [PMID: 34206203 PMCID: PMC8304986 DOI: 10.3390/jpm11070589] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 06/16/2021] [Accepted: 06/20/2021] [Indexed: 12/23/2022] Open
Abstract
Stem cells from human exfoliated deciduous teeth (SHEDs) are considered a type of mesenchymal stem cells (MSCs) because of their unique origin from the neural crest. SHEDs can self-renewal and multi-lineage differentiation with the ability to differentiate into odontoblasts, osteoblast, chondrocytes, neuronal cells, hepatocytes, adipocytes, etc. They are emerging as an ideal source of MSCs because of their easy availability and extraordinary cell number. Ascorbic acid, or vitamin C, has many cell-based applications, such as bone regeneration, osteoblastic differentiation, or extracellular matrix production. It also impacts stem cell plasticity and the ability to sustain pluripotent activity. In this study, we evaluate the effects of ascorbic acid on stemness, paracrine secretion, and differentiation into osteoblast, chondrocytes, and adipocytes. SHEDs displayed enhanced multifaceted activity, which may have applications in regenerative therapy.
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Affiliation(s)
- Shilpa Bhandi
- Department of Restorative Dental Sciences, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia; (S.B.); (M.M.); (N.H.M.A.)
| | - Ahmed Alkahtani
- Department of Restorative Dental Sciences, Division of Endodontics, College of Dentistry, King Saud University, Riyadh 11451, Saudi Arabia; (A.A.); (M.F.A.)
| | - Mohammed Mashyakhy
- Department of Restorative Dental Sciences, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia; (S.B.); (M.M.); (N.H.M.A.)
| | - Abdulaziz S. Abumelha
- Department of Restorative Dental Sciences, College of Dentistry, King Khalid University, Abha 61421, Saudi Arabia;
| | - Nassreen Hassan Mohammad Albar
- Department of Restorative Dental Sciences, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia; (S.B.); (M.M.); (N.H.M.A.)
| | - Apathsakayan Renugalakshmi
- Department of Preventive Dental Sciences, Pedodontics Division, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia;
| | - Mazen F. Alkahtany
- Department of Restorative Dental Sciences, Division of Endodontics, College of Dentistry, King Saud University, Riyadh 11451, Saudi Arabia; (A.A.); (M.F.A.)
| | - Ali Robaian
- Department of Conservative Dental Sciences, College of Dentistry, Prince Sattam bin Abdulaziz University, Alkharj 11942, Saudi Arabia;
| | - Asma Saleh Almeslet
- Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, Riyadh Elm University, Riyadh 12611, Saudi Arabia;
| | | | - Saranya Varadarajan
- Department of Oral Pathology and Microbiology, Sri Venkateswara Dental College and Hospital, Chennai 600130, India;
| | - Thodur Madapusi Balaji
- Department of Periodontology, Tagore Dental College and Hospital, Chennai 600127, India;
| | - Rodolfo Reda
- Department of Oral and Maxillofacial Sciences, Sapienza University of Rome, 00161 Rome, Italy; (R.R.); (L.T.)
| | - Luca Testarelli
- Department of Oral and Maxillofacial Sciences, Sapienza University of Rome, 00161 Rome, Italy; (R.R.); (L.T.)
| | - Shankargouda Patil
- Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia
- Correspondence:
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25
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Xie YH, Tang CQ, Huang ZZ, Zhou SC, Yang YW, Yin Z, Heng BC, Chen WS, Chen X, Shen WL. ECM remodeling in stem cell culture: a potential target for regulating stem cell function. TISSUE ENGINEERING PART B-REVIEWS 2021; 28:542-554. [PMID: 34082581 DOI: 10.1089/ten.teb.2021.0066] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Stem cells (SCs) hold great potential for regenerative medicine, tissue engineering and cell therapy. The clinical applications of SCs require both high quality and quantity of transplantable cells. However, during conventional in vitro expansion, SCs tend to lose properties that make them amenable for cell therapies. Extracellular matrix (ECM) serves an essential regulatory part in the growth, differentiation and homeostasis of all cells in vivo. when signals transmitted to cells, they do not respond passively. Many cell types can remodel pericellular matrix to meet their specific needs. This reciprocal cell-ECM interaction is crucial for the conservation of cell and tissue functions and homeostasis. In vitro ECM remodeling also plays a key role in regulating the lineage fate of SCs. A deeper understanding of in vitro ECM remodeling may provide new perspectives for the maintenance of SC function. In this review, we critically examined three ways that cells can be used to influence the pericellular matrix: (i) exerting tensile force on the ECM, (ii) secreting a variety of ECM proteins, and (iii) degrading the surrounding matrix, and its impact on SC lineage fate. Finally, we describe the deficiencies of current studies and what needs to be done next to further understand the role of ECM remodeling in ex vivo SC cultures.
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Affiliation(s)
- Yuan-Hao Xie
- Zhejiang University School of Medicine Second Affiliated Hospital, 89681, Department of Orthopedic Surgery, Hangzhou, Zhejiang, China;
| | - Chen-Qi Tang
- Zhejiang University School of Medicine Second Affiliated Hospital, 89681, Department of Orthopedic Surgery, Hangzhou, Zhejiang, China;
| | - Zi-Zhan Huang
- Zhejiang University School of Medicine Second Affiliated Hospital, 89681, Department of Orthopedic Surgery, Hangzhou, Zhejiang, China;
| | - Si-Cheng Zhou
- Zhejiang University School of Medicine Second Affiliated Hospital, 89681, Hangzhou, Zhejiang, China;
| | - Yu-Wei Yang
- Zhejiang University School of Medicine, 26441, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Hangzhou, Zhejiang, China;
| | - Zi Yin
- Zhejiang University School of Medicine, 26441, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Hangzhou, Zhejiang, China;
| | - Boon Chin Heng
- Peking University School of Stomatology, 159460, Beijing, Beijing, China;
| | - Wei-Shan Chen
- Zhejiang University School of Medicine Second Affiliated Hospital, 89681, Department of Orthopedic Surgery, Hangzhou, Zhejiang, China;
| | - Xiao Chen
- Zhejiang University School of Medicine, 26441, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Hangzhou, Zhejiang, China;
| | - Wei-Liang Shen
- Zhejiang University School of Medicine Second Affiliated Hospital, 89681, Department of Orthopedic Surgery, Hangzhou, Zhejiang, China;
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26
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Huang X, Li Z, Liu A, Liu X, Guo H, Wu M, Yang X, Han B, Xuan K. Microenvironment Influences Odontogenic Mesenchymal Stem Cells Mediated Dental Pulp Regeneration. Front Physiol 2021; 12:656588. [PMID: 33967826 PMCID: PMC8100342 DOI: 10.3389/fphys.2021.656588] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 03/23/2021] [Indexed: 12/21/2022] Open
Abstract
Dental pulp as a source of nutrition for the whole tooth is vulnerable to trauma and bacterial invasion, which causes irreversible pulpitis and pulp necrosis. Dental pulp regeneration is a valuable method of restoring the viability of the dental pulp and even the whole tooth. Odontogenic mesenchymal stem cells (MSCs) residing in the dental pulp environment have been widely used in dental pulp regeneration because of their immense potential to regenerate pulp-like tissue. Furthermore, the regenerative abilities of odontogenic MSCs are easily affected by the microenvironment in which they reside. The natural environment of the dental pulp has been proven to be capable of regulating odontogenic MSC homeostasis, proliferation, and differentiation. Therefore, various approaches have been applied to mimic the natural dental pulp environment to optimize the efficacy of pulp regeneration. In addition, odontogenic MSC aggregates/spheroids similar to the natural dental pulp environment have been shown to regenerate well-organized dental pulp both in preclinical and clinical trials. In this review, we summarize recent progress in odontogenic MSC-mediated pulp regeneration and focus on the effect of the microenvironment surrounding odontogenic MSCs in the achievement of dental pulp regeneration.
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Affiliation(s)
- Xiaoyao Huang
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Zihan Li
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Anqi Liu
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Xuemei Liu
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Hao Guo
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Meiling Wu
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Xiaoxue Yang
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Bing Han
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Kun Xuan
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
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27
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Xia K, Chen Z, Chen J, Xu H, Xu Y, Yang T, Zhang Q. RGD- and VEGF-Mimetic Peptide Epitope-Functionalized Self-Assembling Peptide Hydrogels Promote Dentin-Pulp Complex Regeneration. Int J Nanomedicine 2020; 15:6631-6647. [PMID: 32982223 PMCID: PMC7495350 DOI: 10.2147/ijn.s253576] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 07/15/2020] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Cell-based tissue engineering is a promising method for dentin-pulp complex (DPC) regeneration. The challenges associated with DPC regeneration include the generation of a suitable microenvironment that facilitates the complete odontogenic differentiation of dental pulp stem cells (DPSCs) and the rapid induction of angiogenesis. Thus, the survival and subsequent differentiation of DPSCs are limited. Extracellular matrix (ECM)-like biomimetic hydrogels composed of self-assembling peptides (SAPs) were developed to provide an appropriate microenvironment for DPSCs. For functional DPC regeneration, the most important considerations are to provide an environment that promotes the adequate attachment of DPSCs and rapid vascularization of the regenerating pulp. Morphogenic signals in the form of growth factors (GFs) have been incorporated into SAPs to promote productive DPSC behaviors. However, the use of GFs has several drawbacks. We envision using a scaffold with SAPs coupled with long-term factors to increase DPSC attachment and vascularization as a method to address this challenge. METHODS In this study, we developed synthetic material for an SAP-based scaffold with RGD- and vascular endothelial growth factor (VEGF)-mimetic peptide epitopes with the dual functions of dentin and pulp regeneration. DPSCs and human umbilical vein endothelial cells (HUVECs) were used to evaluate the biological effects of SAP-based scaffolds. Furthermore, the pulpotomized molar rat model was employed to test the reparative and regenerative effects of SAP-based scaffolds. RESULTS This scaffold simultaneously presented RGD- and VEGF-mimetic peptide epitopes and provided a 3D microenvironment for DPSCs. DPSCs grown on this composite scaffold exhibited significantly improved survival and angiogenic and odontogenic differentiation in the multifunctionalized group in vitro. Histological and functional evaluations of a partially pulpotomized rat model revealed that the multifunctionalized scaffold was superior to other options with respect to stimulating pulp recovery and dentin regeneration in vivo. CONCLUSION Based on our data obtained with the functionalized SAP scaffold, a 3D microenvironment that supports stem cell adhesion and angiogenesis was generated that has great potential for dental pulp tissue engineering and regeneration.
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Affiliation(s)
- Kun Xia
- Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai200072, People’s Republic of China
- Department of Preventive Dentistry, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou325027, People’s Republic of China
| | - Zhuo Chen
- Department of Endodontics, The Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou310006, People’s Republic of China
- Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Stomatology, Hangzhou310006, People’s Republic of China
| | - Jie Chen
- Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai200072, People’s Republic of China
| | - Huaxing Xu
- Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai200072, People’s Republic of China
| | - Yunfei Xu
- Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai200072, People’s Republic of China
| | - Ting Yang
- Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai200072, People’s Republic of China
| | - Qi Zhang
- Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai200072, People’s Republic of China
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28
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Kucukkaya Eren S, Bahador Zırh E, Zeybek ND, Askerbeyli Örs S, Aksel H, Parashos P. Effect of benzalkonium chloride addition to EDTA on attachment and proliferation of dental pulp stem cells on dentin and on transforming growth factor-β1 release. Odontology 2020; 109:313-320. [PMID: 32770280 DOI: 10.1007/s10266-020-00545-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 07/29/2020] [Indexed: 12/15/2022]
Abstract
To investigate the effect of benzalkonium chloride (BAC) addition to ethylenediaminetetraacetic acid (EDTA) on transforming growth factor-β1 (TGF-β1) release, as well as attachment and proliferation of dental pulp stem cells (DPSCs) on dentin. A total of standard 268 human dentin disks were prepared and immersed in 1.5% sodium hypochlorite (NaOCl) for 5 min. The disks were rinsed with distilled water and randomly divided into seven groups. In control group, the disks received no further treatment. The remaining disks were immersed in following solutions: 17% EDTA or 17% EDTA + 0.008% BAC for 1, 5 or 10 min and rinsed with distilled water. DPSCs were seeded in part of the disks since the TGF-β1 release assay was performed with disks with and without cells. The attachment and proliferation of DPSCs on dentin disks were analyzed using lactate dehydrogenase activity and WST-1 assays, respectively. The cell morphology was observed by scanning electron microscopy. The release of TGF-β1 was quantified using ELISA. Data were analyzed using three- and two-way analysis of variance with Bonferroni corrections. Both EDTA solutions increased the attachment and proliferation of DPSCs (p < .05) while there was no significant difference between them (p > .05). The exposure time of both EDTA solutions had no influence on cell attachment, proliferation and TGF-β1 release (p > .05). There was no significant difference in TGF-β1 release between the control and experimental groups (p > .05). The amount of released TGF-β1 from dentin disks was similar whether or not they were seeded with cells (p > .05). Dentin treatment with either of the EDTA solutions had no effect on the amount of TGF-β1 release while both EDTA solutions improved cell attachment and proliferation on dentin surface regardless of exposure time.
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Affiliation(s)
- Selen Kucukkaya Eren
- Department of Endodontics, Faculty of Dentistry, Hacettepe University, 06100, Ankara, Turkey.
| | - Elham Bahador Zırh
- Department of Histology and Embryology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Naciye Dilara Zeybek
- Department of Histology and Embryology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Sevinc Askerbeyli Örs
- Department of Endodontics, Faculty of Dentistry, Hacettepe University, 06100, Ankara, Turkey
| | - Hacer Aksel
- Department of Endodontics, Faculty of Dentistry, Hacettepe University, 06100, Ankara, Turkey.,Department of Periodontics and Endodontics, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA
| | - Peter Parashos
- Melbourne Dental School, University of Melbourne, Melbourne, VIC, Australia
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29
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Hadjichristou C, Papachristou E, Bonovolias I, Bakopoulou A. Three-dimensional tissue engineering-based Dentin/Pulp tissue analogue as advanced biocompatibility evaluation tool of dental restorative materials. Dent Mater 2019; 36:229-248. [PMID: 31791732 DOI: 10.1016/j.dental.2019.11.013] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 11/04/2019] [Accepted: 11/15/2019] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Two-dimensional (2D) in vitro models have been extensively utilized for cytotoxicity assessment of dental materials, but with certain limitations in terms of direct in vitro-in vivo extrapolation (IVIVE). Three-dimensional (3D) models seem more appropriate, recapitulating the structure of human tissues. This study established a 3D dentin/pulp analogue, as advanced cytotoxicity assessment tool of dental restorative materials (DentCytoTool). METHODS DentCytoTool comprised two compartments: the upper, representing the dentin component, with a layer of odontoblast-like cells expanded on microporous membrane of a cell culture insert and covered by a treated dentin matrix; and the lower, representing a pulp analogue, incorporating HUVEC/SCAP co-cultures into collagen I/fibrin hydrogels. Representative resinous monomers (HEMA: 1-8mM; TEGDMA: 0.5-5mM) and bacterial components (LPS: 1μg/ml) were applied into the construct. Cytotoxicity was assessed by MTT and LDH assays, live/dead staining and real-time PCR for odontogenesis- and angiogenesis-related markers. RESULTS DentCytoTool supported cell viability and promoted capillary-like network formation inside the pulp analogue. LPS induced expression of odontogenesis-related markers (RUNX2, ALP, DSPP) without compromising viability of the odontoblast-like cells, while co-treatment with LPS and resin monomers induced cytotoxic effects (live/dead staining, MTT and LDH assays) in cells of both upper and lower compartments and reduced expression angiogenesis-related markers (VEGF, VEGFR2, ANGPT-1, Tie-2, PECAM-1) in a concentration- and time- dependent manner. LPS treatment aggravated TEGDMA-induced and -in certain concentrations (2-4mM)- HEMA-induced cytotoxicity. SIGNIFICANCE DentCytoTool represents a promising tissue-engineering-based cytotoxicity assessment tool, providing more insight into the mechanistic aspects of interactions of dental materials to the dentin/pulp complex.
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Affiliation(s)
- Christina Hadjichristou
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki (A.U.Th), GR-54124 Thessaloniki, Greece
| | - Eleni Papachristou
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki (A.U.Th), GR-54124 Thessaloniki, Greece
| | - Ioannis Bonovolias
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki (A.U.Th), GR-54124 Thessaloniki, Greece
| | - Athina Bakopoulou
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki (A.U.Th), GR-54124 Thessaloniki, Greece.
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30
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Zhang M, Ni S, Zhang X, Lu J, Gao S, Yang Y, Wang Z, Sun H, Li Y. Dexamethasone-loaded hollow hydroxyapatite microsphere promotes odontogenic differentiation of human dental pulp cells in vitro. Odontology 2019; 108:222-230. [PMID: 31598795 DOI: 10.1007/s10266-019-00459-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Accepted: 09/08/2019] [Indexed: 12/28/2022]
Abstract
A sustained-release system was established by synthesis of dexamethasone-loaded hollow hydroxyapatite microspheres (DHHAM). The in vitro effect of DHHAM on odontogenic differentiation of human dental pulp cells (hDPCs) was evaluated. Hollow hydroxyapatite microspheres (HHAM) are successfully manufactured using simple biomimetic one-step strategy in the presence of glycine and sodium dodecyl sulfonate. Dexamethasone (DEX) was loaded to the system after the formation of HHAM. The drug encapsulation capacity of DEX in HHAM is 40.3% and its loading efficiency is 16.7%. The cumulative release of DEX in vitro is 55% up to 35 days. Results of Real-time Polymerase Chain Reaction (Real-time PCR), alkaline phosphatase (ALP) activity and Alizarin Red S staining revealed that DHHAM can obviously promote bio-mineralization of hDPCs in the absence of osteogenic medium and enhance the gene expression of ALP, Runt-related transcription factor 2 (RUNX2), osteocalcin, dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP1). The data suggest that sustained release of DEX from DHHAM could efficiently enhance odontogenic differentiation of hDPCs.
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Affiliation(s)
- Menglin Zhang
- Department of Pediatric Dentistry, School of Stomatology, Jilin University, Changchun, 130021, China
| | - Shilei Ni
- Department of Pathology, School of Stomatology, Jilin University, Changchun, 130021, China
| | - Xue Zhang
- Department of Pediatric Dentistry, School of Stomatology, Jilin University, Changchun, 130021, China
| | - Jinjin Lu
- Department of Pediatric Dentistry, School of Stomatology, Jilin University, Changchun, 130021, China
| | - Siyu Gao
- Department of Pediatric Dentistry, School of Stomatology, Jilin University, Changchun, 130021, China
| | - Yalan Yang
- Department of Pediatric Dentistry, School of Stomatology, Jilin University, Changchun, 130021, China
| | - Zhe Wang
- Department of Pediatric Dentistry, School of Stomatology, Jilin University, Changchun, 130021, China
| | - Hongchen Sun
- School of Stomatology, China Medical University, Shenyang, 110001, China
| | - Yi Li
- Department of Pediatric Dentistry, School of Stomatology, Jilin University, Changchun, 130021, China.
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Kaneko T, Gu B, Sone PP, Zaw SYM, Murano H, Zaw ZCT, Okiji T. Dental Pulp Tissue Engineering Using Mesenchymal Stem Cells: a Review with a Protocol. Stem Cell Rev Rep 2018; 14:668-676. [PMID: 29804171 DOI: 10.1007/s12015-018-9826-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Mesenchymal stem cells (MSCs) are adult stem cells that can be isolated from human and animal sources such as rats. Recently, an in vivo protocol for pulp tissue engineering using implantation of bone marrow MSCs into rat pulpotomized molars was established by our research group. This coronal pulp regeneration model showed almost complete regeneration/healing with dentin bridge formation when the cavity was sealed with mineral trioxide aggregate (MTA) to create a biocompatible seal of the pulp. This method is a powerful tool for elucidating the processes of dental pulp tissue regeneration following implantation of MSCs. In the present review, we discuss the literature in the field of dental pulp tissue engineering using MSCs including dental pulp stem cells and stem cells from exfoliated deciduous teeth. In addition, we present a brief step-by-step protocol of the coronal pulp regeneration model focusing on the implantation of rat bone marrow MSCs, biodegradable scaffolds, and hydrogels in pulpotomized rat molars. The protocol may lay the foundation for studies aiming at defining further histological and molecular mechanism of the rat pulp tissue engineering.
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Affiliation(s)
- Tomoatsu Kaneko
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-Ku, Tokyo, 113-8549, Japan.
| | - Bin Gu
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-Ku, Tokyo, 113-8549, Japan
| | - Phyo Pyai Sone
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-Ku, Tokyo, 113-8549, Japan
| | - Su Yee Myo Zaw
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-Ku, Tokyo, 113-8549, Japan
| | - Hiroki Murano
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-Ku, Tokyo, 113-8549, Japan
| | - Zar Chi Thein Zaw
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-Ku, Tokyo, 113-8549, Japan
| | - Takashi Okiji
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-Ku, Tokyo, 113-8549, Japan
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Kim SG, Malek M, Sigurdsson A, Lin LM, Kahler B. Regenerative endodontics: a comprehensive review. Int Endod J 2018; 51:1367-1388. [PMID: 29777616 DOI: 10.1111/iej.12954] [Citation(s) in RCA: 246] [Impact Index Per Article: 35.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 05/14/2018] [Indexed: 12/13/2022]
Abstract
The European Society of Endodontology and the American Association for Endodontists have released position statements and clinical considerations for regenerative endodontics. There is increasing literature on this field since the initial reports of Iwaya et al. (Dental Traumatology, 17, 2001, 185) and Banchs & Trope (Journal of Endodontics, 30, 2004, 196). Endogenous stem cells from an induced periapical bleeding and scaffolds using blood clot, platelet rich plasma or platelet-rich fibrin have been utilized in regenerative endodontics. This approach has been described as a 'paradigm shift' and considered the first treatment option for immature teeth with pulp necrosis. There are three treatment outcomes of regenerative endodontics; (i) resolution of clinical signs and symptoms; (ii) further root maturation; and (iii) return of neurogenesis. It is known that results are variable for these objectives, and true regeneration of the pulp/dentine complex is not achieved. Repair derived primarily from the periodontal and osseous tissues has been shown histologically. It is hoped that with the concept of tissue engineering, namely stem cells, scaffolds and signalling molecules, that true pulp regeneration is an achievable goal. This review discusses current knowledge as well as future directions for regenerative endodontics. Patient-centred outcomes such as tooth discolouration and possibly more appointments with the potential for adverse effects needs to be discussed with patients and parents. Based on the classification of Cvek (Endodontics and Dental Traumatology, 8, 1992, 45), it is proposed that regenerative endodontics should be considered for teeth with incomplete root formation although teeth with near or complete root formation may be more suited for conventional endodontic therapy or MTA barrier techniques. However, much is still not known about clinical and biological aspects of regenerative endodontics.
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Affiliation(s)
- S G Kim
- Division of Endodontics, Columbia University College of Dental Medicine, New York, NY, USA
| | - M Malek
- Department of Endodontics, New York University College of Dentistry, New York, NY, USA
| | - A Sigurdsson
- Department of Endodontics, New York University College of Dentistry, New York, NY, USA
| | - L M Lin
- Department of Endodontics, New York University College of Dentistry, New York, NY, USA
| | - B Kahler
- The University of Queensland School of Dentistry, Brisbane, Australia
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33
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Tu S, Zheng J, Gao X, Guan C, Cai B, Xiang L. The role of Foxq1 in proliferation of human dental pulp stem cell. Biochem Biophys Res Commun 2018; 497:543-549. [PMID: 29453987 DOI: 10.1016/j.bbrc.2018.02.077] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Accepted: 02/07/2018] [Indexed: 12/19/2022]
Abstract
This study aimed to investigate the role for Foxq1 in proliferation activity regulation of dental pulp stem cells (DPSCs). Proliferation of DPSC was induced by calcium hydroxide, then expression alteration of Foxq1 was evaluated. Lentivirus was employed to manipulate Foxq1 level in DPSC, and proliferation activities were evaluated. To look into mechanism regulating Foxq1 level after calcium hydroxide stimulation, expressions of various microRNAs were evaluated, then bioinformatics study and dual-luciferase study were carried out to confirm targeting relationship between microRNA and Foxq1. The result of our study indicated that proliferation activities of DPSCs were enhanced after calcium hydroxide stimulation, during which expression of Foxq1 was also up-regulated. Cell viability and progression from G1 to S phase were both improved with overexpression of Foxq1, and microRNAs profiling study and dual-luciferase result suggested miR-320b contributed to the up-regulation of Foxq1 after calcium hydroxide stimulation. These results suggested that miR-320b mediated Foxq1 up-regulation promote proliferation of dental pulp stem cells.
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Affiliation(s)
- Shaoqin Tu
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, Guangdong, 510055, China
| | - Junming Zheng
- Foshan Stomatology Hospital, School of Stomatology and Medicine, Foshan University, No. 5, Hebin Road, Chancheng District, Foshan, Guangdong, 528000, China
| | - Xin Gao
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, Guangdong, 510055, China
| | - Chenyu Guan
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, Guangdong, 510055, China
| | - Bin Cai
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, Guangdong, 510055, China
| | - Lusai Xiang
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, Guangdong, 510055, China.
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Abstract
INTRODUCTION Human dental stem cells can be obtained from postnatal teeth, extracted wisdom teeth or exfoliated deciduous teeth. Due to their differentiation potential, these mesenchymal stem cells are promising for tooth repair. Therefore, the development of dental tissue regeneration represents a suitable but challenging, target for dental stem cell therapies. Areas covered: Expert opinion: AREAS COVERED In this review, the authors provide an overview of human dental stem cells and their properties for regeneration medicine. Numerous preclinical studies have shown that dental stem cells improve bone augmentation and healing of periodontal diseases. Clinical trials are ongoing to validate the clinical feasibility of these approaches. Dental stem cells are also important for basic research. EXPERT OPINION Dental stem cells offer numerous advantages for tooth repair and regeneration. Data obtained from different studies are encouraging. In the next few years, investigations on dental stem cells in basic research, pre-clinical research and clinical studies will pave the way to optimizing patient-tailored treatments for repair and regeneration of dental tissues.
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Affiliation(s)
- Christian Morsczeck
- a Department of Cranio-Maxillofacial Surgery , Hospital of the University of Regensburg , Regensburg , Germany
| | - Torsten E Reichert
- a Department of Cranio-Maxillofacial Surgery , Hospital of the University of Regensburg , Regensburg , Germany
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35
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Zhang X, Li H, Sun J, Luo X, Yang H, Xie L, Yang B, Guo W, Tian W. Cell-derived micro-environment helps dental pulp stem cells promote dental pulp regeneration. Cell Prolif 2017; 50. [PMID: 28741725 DOI: 10.1111/cpr.12361] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2017] [Accepted: 05/19/2017] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVES The function of the dental pulp is closely connected to the extracellular matrix (ECM) structure, and ECM has received significant attention due to its biological functions for regulating cells. As such, the interaction between the ECM niche and cells is worth exploring for potential clinical uses. MATERIALS AND METHODS In this study, dental pulp stem cell (DPSC)-derived ECM (DPM) was prepared through cell culture and decellularization to function as the cell niche, and changes in DPSC behaviour and histological analysis of dental pulp tissue regeneration were evaluated following the DPM culture. DPM promoted the replication of DPSCs and exhibited retention of their mineralization. Then, the DPM-based culture strategy under odontogenic culture medium was further investigated, and the mineralization-related markers showed that DPSCs were regulated towards odontogenic differentiation. Dental pulp-like tissue with well-arranged ECM was harvested after a 2-month subcutaneous implantation in nude mice with DPM application. Additionally, DPSCs cultured on the plastic culture surface showed the up-regulation of mineralization makers in vitro, but there was a disorder in matrix formation and mineralization when the cells were cultured in vivo. RESULTS AND CONCLUSIONS DPM-based cultivation could serve as a cell niche and modulate DPSC behaviour, and this method also provided an alternative to harvest tissue-specific ECM and provided a strategy for ECM-cell interaction.
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Affiliation(s)
- Xuexin Zhang
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Stomatology, Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing, China.,State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Hui Li
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jingjing Sun
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xiangyou Luo
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Hefeng Yang
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Li Xie
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Bo Yang
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Weihua Guo
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Pediatric, West China College of Stomatology, Sichuan University, Chengdu, China
| | - Weidong Tian
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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