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Xu Z, Wang Y, Li S, Li Y, Chang L, Yao Y, Peng Q. Advances of functional nanomaterials as either therapeutic agents or delivery systems in the treatment of periodontitis. BIOMATERIALS ADVANCES 2025; 175:214326. [PMID: 40300444 DOI: 10.1016/j.bioadv.2025.214326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 04/20/2025] [Accepted: 04/26/2025] [Indexed: 05/01/2025]
Abstract
Periodontitis is a common chronic inflammatory disease primarily caused by pathogenic microorganisms in the oral cavity. Without appropriate treatments, it may lead to the gradual destruction of the supporting tissues of the teeth. While current treatments can alleviate symptoms, they still have limitations, particularly in eliminating pathogenic bacteria, promoting periodontal tissue regeneration, and avoiding antibiotic resistance. In recent years, functional nanomaterials have shown great potential in the treatment of periodontitis due to their unique physicochemical and biological properties. This review summarizes various functionalization strategies of nanomaterials and explores their potential applications in periodontitis treatment, including metal-based nanoparticles, carbon nanomaterials, polymeric nanoparticles, and exosomes. The mechanisms and advances in antibacterial effects, immune regulation, reactive oxygen species (ROS) scavenging, and bone tissue regeneration are discussed in detail. In addition, the challenges and future directions of applying nanomaterials in periodontitis therapy are also discussed.
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Affiliation(s)
- Ziyi Xu
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Yue Wang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Shuoshun Li
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Yuanhong Li
- Department of Orthodontics, Shanghai Stomatological Hospital and School of Stomatology, Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, China
| | - Lili Chang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Yang Yao
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
| | - Qiang Peng
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
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Yi K, Zhu H, Lian X, Tang Z, Li Q. I-PRF functionalized gelatin methacrylate microspheres for improving the proliferation and osteogenic differentiation of human periodontal ligament stem cells. Biomed Mater 2025; 20:035023. [PMID: 40132260 DOI: 10.1088/1748-605x/adc52a] [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: 09/27/2024] [Accepted: 03/25/2025] [Indexed: 03/27/2025]
Abstract
Although human periodontal ligament stem cell (hPDLSC)-based tissue engineering have been promising for regenerating periodontal bone tissue, their effectiveness is limited by the lack of an optimal delivery vehicle for these cells. Therefore, this study reports a gelatin methacryloyl microsphere system, incorporating injectable platelet-rich fibrin and nano-hydroxyapatite (nHA) as carriers for hPDLSCs. These hybrid microspheres were effectively produced using droplet microfluidics technology, achieving a size range of 100-300 μm. Importantly, the release profile of multiple growth factors (GFs) from the microspheres was significantly extended, lasting up to 28 d. Moreover, the released GFs and nHA considerably enhanced the proliferation of encapsulated hPDLSCs along with their spreading and osteogenic differentiation. The microspheres facilitated the development of Spheroid-like cell aggregates within two weeks of culture, demonstrating a promising approach for advanced periodontal bone tissue regeneration.
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Affiliation(s)
- Ke Yi
- Second Clinical Division, Peking University School and Hospital of Stomatology, Beijing 100101, People's Republic of China
- National Center for Stomatology, Beijing 100081, People's Republic of China
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, People's Republic of China
| | - Huilin Zhu
- Second Clinical Division, Peking University School and Hospital of Stomatology, Beijing 100101, People's Republic of China
- National Center for Stomatology, Beijing 100081, People's Republic of China
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, People's Republic of China
| | - Xiaodong Lian
- Department of Chemistry, Renmin University of China, Beijing 100872, People's Republic of China
| | - Zhihui Tang
- Second Clinical Division, Peking University School and Hospital of Stomatology, Beijing 100101, People's Republic of China
| | - Qing Li
- Second Clinical Division, Peking University School and Hospital of Stomatology, Beijing 100101, People's Republic of China
- National Center for Stomatology, Beijing 100081, People's Republic of China
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, People's Republic of China
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Hu M, Zhang Q, Xu J, Xu L, Xu X, Wang J, Song Y. New considerations in selecting donors for dental pulp stem cells: a pilot study. Biomed Eng Online 2025; 24:37. [PMID: 40119437 PMCID: PMC11929365 DOI: 10.1186/s12938-025-01367-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 03/13/2025] [Indexed: 03/24/2025] Open
Abstract
BACKGROUND/PURPOSE Tissue engineering based on stem cell therapy necessitates a substantial quantity of high-quality stem cells. However, current sources face limitations, including narrow donor pools, compromised biological properties due to cryopreservation, and cellular senescence resulting from in vitro passaging and expansion. This study examines the impact of mild periodontitis on the biological performance of dental pulp stem cells (DPSCs) to explore the potential of broadening the donor pool for these cells. MATERIALS AND METHODS The experiment included two variables: age and the presence of periodontitis. DPSCs were isolated from six healthy subjects and six patients with mild periodontitis. Healthy subjects were categorized into Groups A (28-32 years) and B (52-54 years), and patients with mild periodontitis were categorized into Groups C (31-33 years) and D (50-53 years). The analyses included cell morphology, proliferation rate, multilineage differentiation capacity, apoptosis, and surface marker expression. RESULT No significant differences in cell morphology, pluripotency, or senescence were observed between healthy controls and periodontitis patients across age groups. Additionally, data on proliferation, pluripotency, and senescence were not significantly different. In healthy subjects, increased age was correlated with more elongated, flattened, and broader cells, alongside greater heterogeneity and intercellular granules. The proliferation and differentiation capacities decreased, whereas the degree of apoptosis increased. Similar trends were noted in patients with periodontitis. CONCLUSION The biological properties of DPSCs remain unchanged in teeth with mild periodontitis, providing valuable insights for addressing the shortage of DPSCs in tissue engineering. Teeth with mild periodontitis have the potential to be pulp stem cell donors.
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Affiliation(s)
- Mingchang Hu
- School of Stomatology, Qingdao University, Qingdao, China
| | - Qianqian Zhang
- Department of Orthodontics, Qingdao Stomatological Hospital Affiliated to Qingdao University, No.17 Dexian Road, Shinan District, Qingdao, 266001, Shandong, China
| | - Jidong Xu
- Department of Stomatology, Jiaozhou Central Hospital of Qingdao, Qingdao, China
| | - Linlin Xu
- School of Stomatology, Qingdao University, Qingdao, China
| | - Xuecheng Xu
- Department of Orthodontics, Qingdao Stomatological Hospital Affiliated to Qingdao University, No.17 Dexian Road, Shinan District, Qingdao, 266001, Shandong, China
| | - Jiajia Wang
- School of Stomatology, Binzhou Medical University, Yantai, China
| | - Yu Song
- Department of Orthodontics, Qingdao Stomatological Hospital Affiliated to Qingdao University, No.17 Dexian Road, Shinan District, Qingdao, 266001, Shandong, China.
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Zhou Y, Guo Y, Zhang M, Quan S, Li J. The role of RAP2 in regulation of cell volume on bone marrow mesenchymal stem cell fate determination. J Mol Histol 2025; 56:79. [PMID: 39903386 DOI: 10.1007/s10735-025-10362-1] [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: 07/24/2024] [Accepted: 01/21/2025] [Indexed: 02/06/2025]
Abstract
The extracellular matrix guides cell behavior through mechanical properties, which plays a role in determining cell function and can even influence stem cell fate. Compared with adherent culture, the three-dimensional culture environment is closer to the growth conditions in vivo, but is limited by standardization of material properties and observation and measurement methods. Therefore, it is necessary to study the relationship among the three-dimensional morphological characteristics of cells, cytoskeleton, and stem cell differentiation under adherent culture conditions. Here, we control the cell volume by adjusting the cell density, microfilament cytoskeleton tension, and osmotic pressure of the culture environment, and analyze the cell morphological features and differentiation to the osteoblastic and adipogenic lineages. Based on the in vitro and in vivo results, we identify cell volume as the true reflection of the cytoskeleton tension under stress stimuli compared with cell spreading area. By adjusting cell volume, cytoskeletal tension and cell differentiation can be regulated without affecting cell spreading area. Further study shows that the Ras-related small GTPase RAP2 inhibits the activity of mechanical transducers Lamin A/C and YAP1, playing an important role in cell volume regulation of cell differentiation. In summary, our results support the close relationship between cell volume and cytoskeleton tension. The regulatory role of cell volume on cell differentiation is modulated, at least in part, by RAP2-related mechanosensitive pathways. Our insights into how cell volume regulates cell differentiation may build a bridge between two-dimensional and three-dimensional mechanical studies in cell biology.
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Affiliation(s)
- Yimei Zhou
- State Key Laboratory of Oral Diseases, National Center of Stomatology, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, 14#, 3rd Section, Renmin South Road, Chengdu, 610041, China
| | - Yutong Guo
- Department of Orthodontics, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, Beijing, 100081, PR China
| | - Mei Zhang
- State Key Laboratory of Oral Diseases, National Center of Stomatology, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, 14#, 3rd Section, Renmin South Road, Chengdu, 610041, China
| | - Shuqi Quan
- State Key Laboratory of Oral Diseases, National Center of Stomatology, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, 14#, 3rd Section, Renmin South Road, Chengdu, 610041, China
| | - Juan Li
- State Key Laboratory of Oral Diseases, National Center of Stomatology, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, 14#, 3rd Section, Renmin South Road, Chengdu, 610041, China.
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Zhang Z, Yang D, Yan X, Qiu Q, Guo J, Qiu L. KPNB1-ATF4 induces BNIP3-dependent mitophagy to drive odontoblastic differentiation in dental pulp stem cells. Cell Mol Biol Lett 2024; 29:145. [PMID: 39604846 PMCID: PMC11600598 DOI: 10.1186/s11658-024-00664-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 11/06/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Differentiating dental pulp stem cells (DPSCs) into odontoblasts is a critical process for tooth self-repair and dentine‒pulp engineering strategies in the clinic. However, the mechanism underlying the regulation of DPSC odontoblastic differentiation remains largely unknown. Here, we demonstrated that BCL-2 interacting protein 3 (BNIP3)-dependent mitophagy is associated with importin subunit beta-1 (KPNB1)-activating transcription factor 4 (ATF4), which promotes DPSC odontoblastic differentiation. METHODS The key genes involved in DPSC odontogenic differentiation were identified via bioinformatics. Stable silencing or overexpression of BNIP3 was performed to investigate its impact on DPSC differentiation in vitro (n ≥ 3). To explore the role of BNIP3 in vivo, tooth root fragments loaded with the hydrogel-transfected DPSC complex were implanted into nude mice (n ≥ 6). Dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) polymerase chain reaction (PCR) were conducted to explore the binding site of ATF4 to the BNIP3 promoter (n ≥ 3). Mitochondrial function experiments were performed to investigate the impact of ATF4-BNIP3 on mitochondria (n ≥ 3). Immunoprecipitation (IP) mass spectrometry (MS) was used to investigate the interaction between ATF4 and its binding protein, KPNB1. Plasmids containing wild-type (WT)/mutant (MUT)-nuclear localization signal (NLS) forms of ATF4 were constructed to determine the specific amino acid residues recognized by KPNB1 and their effects on DPSC odontoblastic differentiation (n ≥ 3). RESULTS Compared with those in the control group, the levels of autophagy and mitophagy, especially BNIP3-dependent mitophagy, were greater in the DPSC odontoblastic differentiation group (P < 0.05). Genetic silencing or overexpression of BNIP3 demonstrated that BNIP3 expression was positively correlated with the transition of DPSCs into odontoblasts both in vitro and in vivo (P < 0.05). ATF4 regulates the expression of BNIP3 by directly binding to approximately -1292 to -1279 bp and approximately -1185 to -1172 bp within the BNIP3 promoter region, which is associated with mitophagy and mitochondrial reactive oxygen species (mtROS) levels (P < 0.05). Moreover, ATF4 increased mitophagy, mitochondrial function, and cell differentiation potential via BNIP3 (P < 0.05). Mechanistically, KPNB1 is a novel interacting protein of ATF4 that specifically recognizes amino acids (aa) 280-299 within ATF4 to control its translocation into the nucleus and subsequent transcription and differentiation processes (P < 0.05). CONCLUSIONS We reported that the critical role of KPNB1/ATF4/BNIP3 axis-dependent mitophagy could provide new cues for the regeneration of the dental pulp‒dentin complex in DPSCs.
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Affiliation(s)
- Zeying Zhang
- Department of Endodontics, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, 117 Nanjing North Street, Heping District, Shenyang, Liaoning, 110002, People's Republic of China
| | - Di Yang
- Department of Endodontics, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, 117 Nanjing North Street, Heping District, Shenyang, Liaoning, 110002, People's Republic of China
| | - Xiaoyuan Yan
- Department of Endodontics, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, 117 Nanjing North Street, Heping District, Shenyang, Liaoning, 110002, People's Republic of China
| | - Qiujing Qiu
- Department of Endodontics, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, 117 Nanjing North Street, Heping District, Shenyang, Liaoning, 110002, People's Republic of China
| | - Jiajie Guo
- Department of Endodontics, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, 117 Nanjing North Street, Heping District, Shenyang, Liaoning, 110002, People's Republic of China.
| | - Lihong Qiu
- Department of Endodontics, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, 117 Nanjing North Street, Heping District, Shenyang, Liaoning, 110002, People's Republic of China.
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Wang J, Morita K, Iwata T. Induction of periodontal ligament-derived mesenchymal stromal cell-like cells from human induced pluripotent stem cells. Regen Ther 2024; 26:432-441. [PMID: 39045575 PMCID: PMC11263952 DOI: 10.1016/j.reth.2024.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 05/09/2024] [Accepted: 05/14/2024] [Indexed: 07/25/2024] Open
Abstract
Introduction Periodontal disease is a common oral infection which affects the tooth-supportive tissues directly. Considering the limitation of present regenerative treatments for severe periodontal cases, cytotherapies have been gradually introduced. Human periodontal ligament-derived mesenchymal stromal cells (hPDLMSCs), while identified as one of the promising cell sources for periodontal regenerative therapy, still hold some problems in the clinical application especially their limited life span. To solve the problems, human induced pluripotent stem cells (hiPSCs) are taken into consideration as a robust supply for hPDLMSCs. Methods The induction of hPDLMSCs was performed based on the generation of neural crest-like cells (NCLCs) from hiPSCs. Fibronectin and laminin were tested as coating materials for NCLCs differentiation when following previous protocol, and the characteristics of induced cells were identified by flow cytometry and RT-qPCR for evaluating the induction efficiency. Subsequently, selected dental ectoderm signaling-related cytokines were applied for hPDLMSCs induction for 14 days, and dental mesenchyme-related genes, dental follicle-related genes and hPDL-related genes were tested by RT-qPCR for the evaluation of differentiation. Results Compared to the 58% in laminin-coated condition, fibronectin-coated condition had a higher induction efficiency of CD271high cells as 86% after 8-day induction, while the mesenchymal potential of induced NCLCs was similar between two coating materials.It was shown that the gene expressions of dental mesenchyme, dental follicles and hPDL cells were significantly enhanced with the stimulation of the combination with fibroblast growth factor 8b (FGF8b), FGF2, and bone morphogenetic protein 4 (BMP4). Conclusion FN coating was more effective in NCLCs induction, and the FGF8b+FGF2+BMP4 growth factor cocktail was effective in hPDLMSC-like cell generation. These findings underscored the likely regenerative potential of hiPSCs as an applicable and promising curative strategy for periodontal diseases.
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Affiliation(s)
- Jiacheng Wang
- Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
| | - Kazuki Morita
- Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
| | - Takanori Iwata
- Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
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Chang SY, Chen RS, Chang JYF, Chen MH. The temporospatial relationship between mouse dental pulp stem cells and tooth innervation. J Dent Sci 2024; 19:1075-1082. [PMID: 38618089 PMCID: PMC11010667 DOI: 10.1016/j.jds.2024.02.007] [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: 12/31/2023] [Revised: 02/07/2024] [Indexed: 04/16/2024] Open
Abstract
Background/purpose Dental pulp stem cells (DPSCs) exhibit versatile differentiation capabilities, including neural differentiation, prompting the hypothesis that they may be implicated in the neurodevelopment of teeth. This study aimed to explore the temporospatial dynamics between DPSCs and tooth innervation, employing immunofluorescence staining and fluorescent dye injections to investigate the distribution of DPSCs, neural stem cells (NSCs), nerve growth cones, and sensory nerves in developing mouse tooth germs at various stages. Materials and methods Immunofluorescence staining targeting CD146, Nestin, and GAP-43, along with the injection of AM1-43 fluorescent dye, were utilized to observe the distribution of DPSCs, NSCs, nerve growth cones, and sensory nerves in mouse tooth germs at different developmental stages. Results Positive CD146 immunostaining was observed in microvascular endothelial cells and pericytes within and around the tooth germ. The percentage of CD146-positive cells remained consistent between 4-day-old and 8-day-old second molar tooth germs. Conversely, Nestin expression in odontoblasts and their processes decreased in 8-day-old tooth germs compared to 4-day-old ones. Positive immunostaining for GAP-43 and AM1-43 fluorescence revealed the entry of nerve growth cones and sensory nerves into the pulp in 8-day-old tooth germs, while these elements were confined to the dental follicle in 4-day-old germs. No co-localization of CD146-positive DPSCs with nerve growth cones and sensory nerves was observed. Conclusion DPSCs and NSCs were present in dental pulp tissue before nerves penetrated the pulp. The decline in NSCs after nerve entry suggests a potential role for DPSCs and NSCs in attracting neural growth and/or differentiation within the pulp.
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Affiliation(s)
- Shu-Ya Chang
- Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan
- Department of Prosthodontics, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, Taiwan
| | - Rung-Shu Chen
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Julia Yu Fong Chang
- Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan
- Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Min-Huey Chen
- Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan
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Yang D, Jeong Y, Ortinau L, Solidum J, Park D. Mx1 -labeled pulp progenitor cells are main contributors to postnatal odontoblasts and pulp cells in murine molars. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.03.21.586156. [PMID: 38585950 PMCID: PMC10996506 DOI: 10.1101/2024.03.21.586156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/09/2024]
Abstract
Regeneration of dentin and odontoblasts from dental pulp stem cells (DPSCs) is essential for permanent tooth maintenance. However, the in vivo identity and role of endogenous DPSCs in reparative dentinogenesis are elusive. Here, using pulp single-cell analysis before and after molar eruption, we revealed that endogenous DPSCs are enriched in Cxcl12- GFP + coronal papilla-like cells with Mx1- Cre labeling. These Mx1 + Cxcl12- GFP + cells are long-term repopulating cells that contribute to the majority of pulp cells and new odontoblasts after eruption. Upon molar injury, Mx1 + DPSCs localize into the injury site and differentiate into new odontoblasts, forming scleraxis -GFP + and osteocalcin -GFP + dentinal tubules and reparative dentin. Single-cell and FACS analysis showed that Mx1 + Cxcl12- GFP + DPSCs are the most primitive cells with stem cell marker expression and odontoblast differentiation. Taken together, our findings demonstrate that Mx1 labels postnatal DSPCs, which are the main source of pulp cells and new odontoblasts with reparative dentinogenesis in vivo .
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Kadkhoda Z, Motie P, Rad MR, Mohaghegh S, Kouhestani F, Motamedian SR. Comparison of Periodontal Ligament Stem Cells with Mesenchymal Stem Cells from Other Sources: A Scoping Systematic Review of In vitro and In vivo Studies. Curr Stem Cell Res Ther 2024; 19:497-522. [PMID: 36397622 DOI: 10.2174/1574888x17666220429123319] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 12/31/2021] [Accepted: 03/11/2022] [Indexed: 11/22/2022]
Abstract
OBJECTIVE The application of stem cells in regenerative medicine depends on their biological properties. This scoping review aimed to compare the features of periodontal ligament stem cells (PDLSSCs) with stem cells derived from other sources. DESIGN An electronic search in PubMed/Medline, Embase, Scopus, Google Scholar and Science Direct was conducted to identify in vitro and in vivo studies limited to English language. RESULTS Overall, 65 articles were included. Most comparisons were made between bone marrow stem cells (BMSCs) and PDLSCs. BMSCs were found to have lower proliferation and higher osteogenesis potential in vitro and in vivo than PDLSCs; on the contrary, dental follicle stem cells and umbilical cord mesenchymal stem cells (UCMSCs) had a higher proliferative ability and lower osteogenesis than PDLSCs. Moreover, UCMSCs exhibited a higher apoptotic rate, hTERT expression, and relative telomerase length. The immunomodulatory function of adipose-derived stem cells and BMSCs was comparable to PDLSCs. Gingival mesenchymal stem cells showed less sensitivity to long-term culture. Both pure and mixed gingival cells had lower osteogenic ability compared to PDLSCs. Comparison of dental pulp stem cells (DPSCs) with PDLSCs regarding proliferation rate, osteo/adipogenesis, and immunomodulatory properties was contradictory; however, in vivo bone formation of DPSCs seemed to be lower than PDLSCs. CONCLUSION In light of the performed comparative studies, PDLSCs showed comparable results to stem cells derived from other sources; however, further in vivo studies are needed to determine the actual pros and cons of stem cells in comparison to each other.
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Affiliation(s)
- Zeinab Kadkhoda
- Department of Periodontology, School of Dentistry, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Parisa Motie
- Student Research Committee, School of Dentistry, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Maryam Rezaei Rad
- Dental Research Center, Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sadra Mohaghegh
- Student Research Committee, School of Dentistry, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Farnaz Kouhestani
- Department of Periodontics, School of Dentistry, Bushehr University of Medical Sciences, Tehran, Iran
| | - Saeed Reza Motamedian
- Dentofacial Deformities Research Center, Research Institute of Dental Sciences, Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Hazrati P, Mirtaleb MH, Boroojeni HSH, Koma AAY, Nokhbatolfoghahaei H. Current Trends, Advances, and Challenges of Tissue Engineering-Based Approaches of Tooth Regeneration: A Review of the Literature. Curr Stem Cell Res Ther 2024; 19:473-496. [PMID: 35984017 DOI: 10.2174/1574888x17666220818103228] [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: 04/05/2022] [Revised: 05/17/2022] [Accepted: 06/01/2022] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Tooth loss is a significant health issue. Currently, this situation is often treated with the use of synthetic materials such as implants and prostheses. However, these treatment modalities do not fully meet patients' biological and mechanical needs and have limited longevity. Regenerative medicine focuses on the restoration of patients' natural tissues via tissue engineering techniques instead of rehabilitating with artificial appliances. Therefore, a tissue-engineered tooth regeneration strategy seems like a promising option to treat tooth loss. OBJECTIVE This review aims to demonstrate recent advances in tooth regeneration strategies and discoveries about underlying mechanisms and pathways of tooth formation. RESULTS AND DISCUSSION Whole tooth regeneration, tooth root formation, and dentin-pulp organoid generation have been achieved by using different seed cells and various materials for scaffold production. Bioactive agents are critical elements for the induction of cells into odontoblast or ameloblast lineage. Some substantial pathways enrolled in tooth development have been figured out, helping researchers design their experiments more effectively and aligned with the natural process of tooth formation. CONCLUSION According to current knowledge, tooth regeneration is possible in case of proper selection of stem cells, appropriate design and manufacturing of a biocompatible scaffold, and meticulous application of bioactive agents for odontogenic induction. Understanding innate odontogenesis pathways play a crucial role in accurately planning regenerative therapeutic interventions in order to reproduce teeth.
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Affiliation(s)
- Parham Hazrati
- School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Helia Sadat Haeri Boroojeni
- Oral and Maxillofacial Surgery Department, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Hanieh Nokhbatolfoghahaei
- Dental Research Center, Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Ning J, Zhang L, Xie H, Chai L, Yao J. Decoding the multifaceted signatures and transcriptomic characteristics of stem cells derived from apical papilla and dental pulp of human supernumerary teeth. Cell Biol Int 2023; 47:1976-1986. [PMID: 37641425 DOI: 10.1002/cbin.12088] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 05/07/2023] [Accepted: 08/20/2023] [Indexed: 08/31/2023]
Abstract
Supernumerary teeth are advantaged sources for high-quality stem cell preparation from both apical papilla (SCAP-Ss) and dental pulp (DPSCs). However, the deficiency of the systematic and detailed comparison of the biological and transcriptomic characteristics of the aforementioned stem cells largely hinders their application in regenerative medicine. Herein, we collected supernumerary teeth for SCAP-S and DPSC isolation and identification by utilizing multiple biological tests (e.g., growth curve, cell cycle and apoptosis, adipogenic and osteogenic differentiation, and quantitative real-time polymerase chain reaction). Furthermore, we took advantage of transcriptome sequencing and multifaceted bioinformatic analyses to dissect the similarities and diversities between them. In this study, we found that SCAP-Ss and DPSCs showed indistinctive signatures in morphology and immunophenotypes, whereas with diversity in cell vitality and multi-lineage differentiation as well as gene expression profiling and differentially expressed genes-associated gene ontology and signaling pathways. Collectively, our data indicated the diversity of the multifaceted signatures of human supernumerary teeth-derived stem cells both at the cellular and molecular levels, which also supplied new references for SCAP-Ss serving as splendid alternative stem cell sources for regenerative medicine purposes.
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Affiliation(s)
- Juan Ning
- School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Leisheng Zhang
- NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor & Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, China
- Key Laboratory of Radiation Technology and Biophysics, Hefei Institute of Physical Science, Chinese Academy of Sciences, Hefei, China
- Jiangxi Health-Biotech Stem Cell Technology Co., Ltd., Jiangxi Research Center of Stem Cell Engineering, Shangrao, China
| | - Hanjing Xie
- School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Lian Chai
- School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Jun Yao
- School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
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12
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Jiang X, Li W, Ge L, Lu M. Mesenchymal Stem Cell Senescence during Aging:From Mechanisms to Rejuvenation Strategies. Aging Dis 2023; 14:1651-1676. [PMID: 37196126 PMCID: PMC10529739 DOI: 10.14336/ad.2023.0208] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 02/08/2023] [Indexed: 05/19/2023] Open
Abstract
In cell transplantation therapy, mesenchymal stem cells(MSCs)are ideal seed cells due to their easy acquisition and cultivation, strong regenerative capacity, multi-directional differentiation abilities, and immunomodulatory effects. Autologous MSCs are better applicable compared with allogeneic MSCs in clinical practice. The elderly are the main population for cell transplantation therapy, but as donor aging, MSCs in the tissue show aging-related changes. When the number of generations of in vitro expansion is increased, MSCs will also exhibit replicative senescence. The quantity and quality of MSCs decline during aging, which limits the efficacy of autologous MSCs transplantation therapy. In this review, we examine the changes in MSC senescence as a result of aging, discuss the progress of research on mechanisms and signalling pathways of MSC senescence, and discuss possible rejuvenation strategies of aged MSCs to combat senescence and enhance the health and therapeutic potential of MSCs.
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Affiliation(s)
- Xinchen Jiang
- The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.
- Hunan provincical key laboratory of Neurorestoratology, the Second Affiliated Hospital, Hunan Normal University, Changsha, China.
| | - Wenshui Li
- The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.
- Hunan provincical key laboratory of Neurorestoratology, the Second Affiliated Hospital, Hunan Normal University, Changsha, China.
| | - Lite Ge
- The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.
- Hunan provincical key laboratory of Neurorestoratology, the Second Affiliated Hospital, Hunan Normal University, Changsha, China.
- Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, 410011, China, Changsha
| | - Ming Lu
- The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.
- Hunan provincical key laboratory of Neurorestoratology, the Second Affiliated Hospital, Hunan Normal University, Changsha, China.
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13
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Khan S, Mahgoub S, Fallatah N, Lalor PF, Newsome PN. Liver Disease and Cell Therapy: Advances Made and Remaining Challenges. Stem Cells 2023; 41:739-761. [PMID: 37052348 PMCID: PMC10809282 DOI: 10.1093/stmcls/sxad029] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 02/27/2023] [Indexed: 04/14/2023]
Abstract
The limited availability of organs for liver transplantation, the ultimate curative treatment for end stage liver disease, has resulted in a growing and unmet need for alternative therapies. Mesenchymal stromal cells (MSCs) with their broad ranging anti-inflammatory and immunomodulatory properties have therefore emerged as a promising therapeutic agent in treating inflammatory liver disease. Significant strides have been made in exploring their biological activity. Clinical application of MSC has shifted the paradigm from using their regenerative potential to one which harnesses their immunomodulatory properties. Reassuringly, MSCs have been extensively investigated for over 30 years with encouraging efficacy and safety data from translational and early phase clinical studies, but questions remain about their utility. Therefore, in this review, we examine the translational and clinical studies using MSCs in various liver diseases and their impact on dampening immune-mediated liver damage. Our key observations include progress made thus far with use of MSCs for clinical use, inconsistency in the literature to allow meaningful comparison between different studies and need for standardized protocols for MSC manufacture and administration. In addition, the emerging role of MSC-derived extracellular vesicles as an alternative to MSC has been reviewed. We have also highlighted some of the remaining clinical challenges that should be addressed before MSC can progress to be considered as therapy for patients with liver disease.
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Affiliation(s)
- Sheeba Khan
- National Institute for Health Research, Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, West Midlands, UK
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, West Midlands, UK
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Birmingham, West Midlands, UK
| | - Sara Mahgoub
- National Institute for Health Research, Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, West Midlands, UK
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, West Midlands, UK
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Birmingham, West Midlands, UK
| | - Nada Fallatah
- National Institute for Health Research, Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, West Midlands, UK
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, West Midlands, UK
- Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Patricia F Lalor
- National Institute for Health Research, Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, West Midlands, UK
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, West Midlands, UK
| | - Philip N Newsome
- National Institute for Health Research, Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, West Midlands, UK
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, West Midlands, UK
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Birmingham, West Midlands, UK
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14
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Qian Y, Gong J, Lu K, Hong Y, Zhu Z, Zhang J, Zou Y, Zhou F, Zhang C, Zhou S, Gu T, Sun M, Wang S, He J, Li Y, Lin J, Yuan Y, Ouyang H, Yu M, Wang H. DLP printed hDPSC-loaded GelMA microsphere regenerates dental pulp and repairs spinal cord. Biomaterials 2023; 299:122137. [PMID: 37172537 DOI: 10.1016/j.biomaterials.2023.122137] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 04/21/2023] [Accepted: 04/27/2023] [Indexed: 05/15/2023]
Abstract
Dental pulp regeneration is ideal for irreversible pulp or periapical lesions, and in situ stem cell therapy is one of the most effective therapies for pulp regeneration. In this study, we provided an atlas of the non-cultured and monolayer cultured dental pulp cells with single-cell RNA sequencing and analysis. Monolayer cultured dental pulp cells cluster more closely together than non-cultured dental pulp cells, suggesting a lower heterogeneous population with relatively consistent clusters and similar cellular composition. We successfully fabricated hDPSC-loaded microspheres by layer-by-layer photocuring with a digital light processing (DLP) printer. These hDPSC-loaded microspheres have improved stemness and higher multi-directional differentiation potential, including angiogenic, neurogenic, and odontogenic differentiation. The hDPSC-loaded microspheres could promote spinal cord regeneration in rat spinal cord injury models. Moreover, in heterotopic implantation tests on nude mice, CD31, MAP2, and DSPP immunofluorescence signals were observed, implying the formation of vascular, neural, and odontogenetic tissues. In situ experiments in minipigs demonstrated highly vascularized dental pulp and uniformly arranged odontoblast-like cells in root canals of incisors. In short, hDPSC-loaded microspheres can promote full-length dental pulp regeneration at the root canals' coronal, middle, and apical sections, particularly for blood vessels and nerve formation, which is a promising therapeutic strategy for necrotic pulp.
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Affiliation(s)
- Ying Qian
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China
| | - Jiaxing Gong
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China
| | - Kejie Lu
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China
| | - Yi Hong
- Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Ziyu Zhu
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China
| | - Jingyu Zhang
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China
| | - Yiwei Zou
- Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Feifei Zhou
- Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Chaoying Zhang
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China
| | - Siyi Zhou
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China
| | - Tianyi Gu
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China
| | - Miao Sun
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China
| | - Shaolong Wang
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China
| | - Jianxiang He
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China
| | - Yang Li
- The State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, Zhejiang, 310028, China
| | - Junxin Lin
- Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, And Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, 310058, China
| | - Yuan Yuan
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China; Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, And Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, 310058, China.
| | - Hongwei Ouyang
- Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, And Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, 310058, China.
| | - Mengfei Yu
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China.
| | - Huiming Wang
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, 310006, Zhejiang, China
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15
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Sui BD, Zheng CX, Zhao WM, Xuan K, Li B, Jin Y. Mesenchymal condensation in tooth development and regeneration: a focus on translational aspects of organogenesis. Physiol Rev 2023; 103:1899-1964. [PMID: 36656056 DOI: 10.1152/physrev.00019.2022] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 12/26/2022] [Accepted: 01/16/2023] [Indexed: 01/20/2023] Open
Abstract
The teeth are vertebrate-specific, highly specialized organs performing fundamental functions of mastication and speech, the maintenance of which is crucial for orofacial homeostasis and is further linked to systemic health and human psychosocial well-being. However, with limited ability for self-repair, the teeth can often be impaired by traumatic, inflammatory, and progressive insults, leading to high prevalence of tooth loss and defects worldwide. Regenerative medicine holds the promise to achieve physiological restoration of lost or damaged organs, and in particular an evolving framework of developmental engineering has pioneered functional tooth regeneration by harnessing the odontogenic program. As a key event of tooth morphogenesis, mesenchymal condensation dictates dental tissue formation and patterning through cellular self-organization and signaling interaction with the epithelium, which provides a representative to decipher organogenetic mechanisms and can be leveraged for regenerative purposes. In this review, we summarize how mesenchymal condensation spatiotemporally assembles from dental stem cells (DSCs) and sequentially mediates tooth development. We highlight condensation-mimetic engineering efforts and mechanisms based on ex vivo aggregation of DSCs, which have achieved functionally robust and physiologically relevant tooth regeneration after implantation in animals and in humans. The discussion of this aspect will add to the knowledge of development-inspired tissue engineering strategies and will offer benefits to propel clinical organ regeneration.
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Affiliation(s)
- Bing-Dong Sui
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Chen-Xi Zheng
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Wan-Min Zhao
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Kun Xuan
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
- Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Bei Li
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Yan Jin
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
- Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, Shaanxi, China
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16
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Yang X, Li Q, Liu W, Zong C, Wei L, Shi Y, Han Z. Mesenchymal stromal cells in hepatic fibrosis/cirrhosis: from pathogenesis to treatment. Cell Mol Immunol 2023; 20:583-599. [PMID: 36823236 PMCID: PMC10229624 DOI: 10.1038/s41423-023-00983-5] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 01/29/2023] [Indexed: 02/25/2023] Open
Abstract
Hepatic fibrosis/cirrhosis is a significant health burden worldwide, resulting in liver failure or hepatocellular carcinoma (HCC) and accounting for many deaths each year. The pathogenesis of hepatic fibrosis/cirrhosis is very complex, which makes treatment challenging. Endogenous mesenchymal stromal cells (MSCs) have been shown to play pivotal roles in the pathogenesis of hepatic fibrosis. Paradoxically, exogenous MSCs have also been used in clinical trials for liver cirrhosis, and their effectiveness has been observed in most completed clinical trials. There are still many issues to be resolved to promote the use of MSCs in the clinic in the future. In this review, we will examine the controversial role of MSCs in the pathogenesis and treatment of hepatic fibrosis/cirrhosis. We also investigated the clinical trials involving MSCs in liver cirrhosis, summarized the parameters that need to be standardized, and discussed how to promote the use of MSCs from a clinical perspective.
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Affiliation(s)
- Xue Yang
- Department of Tumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Naval Medical University, Shanghai, 200438, China
- Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Eastern Hepatobiliary Surgery Hospital/National Center for Liver Cancer, Naval Medical University, Shanghai, 200438, China
- The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, State Key Laboratory of Radiation Medicine and Protection, Key Laboratory of Stem Cells and Medical Biomaterials of Jiangsu Province, Medical College of Soochow University, Soochow University, Suzhou, 215000, China
- Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy
| | - Qing Li
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
| | - Wenting Liu
- Department of Tumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Naval Medical University, Shanghai, 200438, China
- Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Eastern Hepatobiliary Surgery Hospital/National Center for Liver Cancer, Naval Medical University, Shanghai, 200438, China
| | - Chen Zong
- Department of Tumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Naval Medical University, Shanghai, 200438, China
- Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Eastern Hepatobiliary Surgery Hospital/National Center for Liver Cancer, Naval Medical University, Shanghai, 200438, China
| | - Lixin Wei
- Department of Tumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Naval Medical University, Shanghai, 200438, China
- Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Eastern Hepatobiliary Surgery Hospital/National Center for Liver Cancer, Naval Medical University, Shanghai, 200438, China
| | - Yufang Shi
- The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, State Key Laboratory of Radiation Medicine and Protection, Key Laboratory of Stem Cells and Medical Biomaterials of Jiangsu Province, Medical College of Soochow University, Soochow University, Suzhou, 215000, China.
- Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy.
| | - Zhipeng Han
- Department of Tumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Naval Medical University, Shanghai, 200438, China.
- Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Eastern Hepatobiliary Surgery Hospital/National Center for Liver Cancer, Naval Medical University, Shanghai, 200438, China.
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17
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Oka H, Ito S, Kawakami M, Sasaki H, Abe S, Matsunaga S, Morita S, Noguchi T, Kasahara N, Tokuyama A, Kasahara M, Katakura A, Yajima Y, Mizoguchi T. Subset of the periodontal ligament expressed leptin receptor contributes to part of hard tissue-forming cells. Sci Rep 2023; 13:3442. [PMID: 36859576 PMCID: PMC9977939 DOI: 10.1038/s41598-023-30446-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 02/23/2023] [Indexed: 03/03/2023] Open
Abstract
The lineage of periodontal ligament (PDL) stem cells contributes to alveolar bone (AB) and cementum formation, which are essential for tooth-jawbone attachment. Leptin receptor (LepR), a skeletal stem cell marker, is expressed in PDL; however, the stem cell capacity of LepR+ PDL cells remains unclear. We used a Cre/LoxP-based approach and detected LepR-cre-labeled cells in the perivascular around the root apex; their number increased with age. In the juvenile stage, LepR+ PDL cells differentiated into AB-embedded osteocytes rather than cementocytes, but their contribution to both increased with age. The frequency of LepR+ PDL cell-derived lineages in hard tissue was < 20% per total cells at 1-year-old. Similarly, LepR+ PDL cells differentiated into osteocytes following tooth extraction, but their frequency was < 9%. Additionally, both LepR+ and LepR- PDL cells demonstrated spheroid-forming capacity, which is an indicator of self-renewal. These results indicate that both LepR+ and LepR- PDL populations contributed to hard tissue formation. LepR- PDL cells increased the expression of LepR during spheroid formation, suggesting that the LepR- PDL cells may hierarchically sit upstream of LepR+ PDL cells. Collectively, the origin of hard tissue-forming cells in the PDL is heterogeneous, some of which express LepR.
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Affiliation(s)
- Hirotsugu Oka
- grid.265070.60000 0001 1092 3624Department of Oral and Maxillofacial Implantology, Tokyo Dental College, Tokyo, 101-0061 Japan
| | - Shinichirou Ito
- grid.265070.60000 0001 1092 3624Department of Pharmacology, Tokyo Dental College, Tokyo, 101-0061 Japan
| | - Mana Kawakami
- grid.265070.60000 0001 1092 3624Department of Oral Pathobiological Science and Surgery, Tokyo Dental College, Tokyo, 101-0061 Japan
| | - Hodaka Sasaki
- grid.265070.60000 0001 1092 3624Department of Oral and Maxillofacial Implantology, Tokyo Dental College, Tokyo, 101-0061 Japan
| | - Shinichi Abe
- grid.265070.60000 0001 1092 3624Department of Anatomy, Tokyo Dental College, Tokyo, 101-0061 Japan ,grid.265070.60000 0001 1092 3624Oral Health Science Center, Tokyo Dental College, Tokyo, 101-0061 Japan ,grid.265070.60000 0001 1092 3624Tokyo Dental College Research Branding Project, Tokyo Dental College, Tokyo, 101-0061 Japan
| | - Satoru Matsunaga
- grid.265070.60000 0001 1092 3624Department of Anatomy, Tokyo Dental College, Tokyo, 101-0061 Japan ,grid.265070.60000 0001 1092 3624Oral Health Science Center, Tokyo Dental College, Tokyo, 101-0061 Japan ,grid.265070.60000 0001 1092 3624Tokyo Dental College Research Branding Project, Tokyo Dental College, Tokyo, 101-0061 Japan
| | - Sumiharu Morita
- grid.265070.60000 0001 1092 3624Department of Anatomy, Tokyo Dental College, Tokyo, 101-0061 Japan
| | - Taku Noguchi
- grid.265070.60000 0001 1092 3624Department of Anatomy, Tokyo Dental College, Tokyo, 101-0061 Japan
| | - Norio Kasahara
- grid.265070.60000 0001 1092 3624Department of Histology and Developmental Biology, Tokyo Dental College, Tokyo, 101-0061 Japan
| | - Akihide Tokuyama
- grid.265070.60000 0001 1092 3624Department of Pharmacology, Tokyo Dental College, Tokyo, 101-0061 Japan
| | - Masataka Kasahara
- grid.265070.60000 0001 1092 3624Department of Pharmacology, Tokyo Dental College, Tokyo, 101-0061 Japan ,grid.265070.60000 0001 1092 3624Oral Health Science Center, Tokyo Dental College, Tokyo, 101-0061 Japan ,grid.265070.60000 0001 1092 3624Tokyo Dental College Research Branding Project, Tokyo Dental College, Tokyo, 101-0061 Japan
| | - Akira Katakura
- grid.265070.60000 0001 1092 3624Department of Oral Pathobiological Science and Surgery, Tokyo Dental College, Tokyo, 101-0061 Japan ,grid.265070.60000 0001 1092 3624Oral Health Science Center, Tokyo Dental College, Tokyo, 101-0061 Japan ,grid.265070.60000 0001 1092 3624Tokyo Dental College Research Branding Project, Tokyo Dental College, Tokyo, 101-0061 Japan
| | - Yasutomo Yajima
- grid.265070.60000 0001 1092 3624Department of Oral and Maxillofacial Implantology, Tokyo Dental College, Tokyo, 101-0061 Japan ,grid.411611.20000 0004 0372 3845MDU Hospital, Implant Center, Matsumoto Dental University, Nagano, 399-0781 Japan
| | - Toshihide Mizoguchi
- Oral Health Science Center, Tokyo Dental College, Tokyo, 101-0061, Japan. .,Tokyo Dental College Research Branding Project, Tokyo Dental College, Tokyo, 101-0061, Japan.
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18
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Leite YKDC, Oliveira ACDJ, Quelemes PV, Neto NMA, de Carvalho CES, Soares Rodrigues HW, Alves MMDM, Carvalho FADA, Arcanjo DDR, da Silva-Filho EC, Durazzo A, Lucarini M, de Carvalho MAM, da Silva DA, Leite JRDSDA. Novel Scaffold Based on Chitosan Hydrogels/Phthalated Cashew Gum for Supporting Human Dental Pulp Stem Cells. Pharmaceuticals (Basel) 2023; 16:266. [PMID: 37259411 PMCID: PMC9960865 DOI: 10.3390/ph16020266] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/26/2023] [Accepted: 02/04/2023] [Indexed: 07/29/2023] Open
Abstract
Hydrogels are structures that have value for application in the area of tissue engineering because they mimic the extracellular matrix. Naturally obtained polysaccharides, such as chitosan (CH) and cashew gum, are materials with the ability to form polymeric networks due to their physicochemical properties. This research aimed to develop a scaffold based on chitosan and phthalated cashew tree gum and test it as a support for the growth of human mesenchymal stem cells. In this study, phthalation in cashew gum (PCG) was performed by using a solvent-free route. PCG-CH scaffold was developed by polyelectrolyte complexation, and its ability to support adherent stem cell growth was evaluated. The scaffold showed a high swelling rate. The pore sizes of the scaffold were analyzed by scanning electron microscopy. Human dental pulp stem cells (hDPSCs) were isolated, expanded, and characterized for their potential to differentiate into mesenchymal lineages and for their immunophenotypic profile. Isolated mesenchymal stem cells presented fibroblastoid morphology, plastic adhesion capacity, and differentiation in osteogenic, adipogenic, and chondrogenic lineages. Mesenchymal stem cells were cultured in scaffolds to assess cell adhesion and growth. The cells seeded on the scaffold showed typical morphology, attachment, and adequate distribution inside the matrix pores. Thus, cells seeded in the scaffold may improve the osteoinductive and osteoconductive properties of these biomaterials.
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Affiliation(s)
- Yulla Klinger de Carvalho Leite
- Integrated Nucleus of Morphology and Stem Cell Research (NUPCelt), Federal University of Piaui, UFPI, Teresina 64049-550, PI, Brazil
| | - Antônia Carla de Jesus Oliveira
- Research Center on Biodiversity and Biotechnology (BIOTEC), Federal University of Delta of Parnaiba, UFDPar, Parnaiba 64202-020, PI, Brazil
| | - Patrick Veras Quelemes
- Research Center on Biodiversity and Biotechnology (BIOTEC), Federal University of Delta of Parnaiba, UFDPar, Parnaiba 64202-020, PI, Brazil
| | - Napoleão Martins Argolo Neto
- Integrated Nucleus of Morphology and Stem Cell Research (NUPCelt), Federal University of Piaui, UFPI, Teresina 64049-550, PI, Brazil
| | - Camila Ernanda Sousa de Carvalho
- Integrated Nucleus of Morphology and Stem Cell Research (NUPCelt), Federal University of Piaui, UFPI, Teresina 64049-550, PI, Brazil
| | - Huanna Waleska Soares Rodrigues
- Integrated Nucleus of Morphology and Stem Cell Research (NUPCelt), Federal University of Piaui, UFPI, Teresina 64049-550, PI, Brazil
| | - Michel Muálem de Moraes Alves
- Department of Veterinary Morphophysiology, Federal University of Piaui, UFPI, Teresina 64049-550, PI, Brazil
- Laboratory of Antileishmania Activity, Medicinal Plants Research Center, Federal University of Piaui, UFPI, Teresina 64049-550, PI, Brazil
| | - Fernando Aécio de Amorim Carvalho
- Laboratory of Antileishmania Activity, Medicinal Plants Research Center, Federal University of Piaui, UFPI, Teresina 64049-550, PI, Brazil
| | - Daniel Dias Rufino Arcanjo
- Laboratory of Antileishmania Activity, Medicinal Plants Research Center, Federal University of Piaui, UFPI, Teresina 64049-550, PI, Brazil
- Laboratory of Functional and Molecular Studies in Physiopharmacology (LAFMOL), Federal University of Piaui, UFPI, Teresina 64049-550, PI, Brazil
| | - Edson Cavalcanti da Silva-Filho
- Interdisciplinary Laboratory for Advanced Materials (LIMAV), Federal University of Piaui, UFPI, Teresina 64049-550, PI, Brazil
| | - Alessandra Durazzo
- CREA-Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy
| | - Massimo Lucarini
- CREA-Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy
| | - Maria Acelina Martins de Carvalho
- Integrated Nucleus of Morphology and Stem Cell Research (NUPCelt), Federal University of Piaui, UFPI, Teresina 64049-550, PI, Brazil
| | - Durcilene Alves da Silva
- Research Center on Biodiversity and Biotechnology (BIOTEC), Federal University of Delta of Parnaiba, UFDPar, Parnaiba 64202-020, PI, Brazil
| | - José Roberto de Souza de Almeida Leite
- Research Center on Biodiversity and Biotechnology (BIOTEC), Federal University of Delta of Parnaiba, UFDPar, Parnaiba 64202-020, PI, Brazil
- Area Morphology, Faculty of Medicine, University of Brasília (UnB), Campus Darcy Ribeiro, Brasília 70910-900, DF, Brazil
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Zhao Z, Liu J, Weir MD, Schneider A, Ma T, Oates TW, Xu HHK, Zhang K, Bai Y. Periodontal ligament stem cell-based bioactive constructs for bone tissue engineering. Front Bioeng Biotechnol 2022; 10:1071472. [PMID: 36532583 PMCID: PMC9755356 DOI: 10.3389/fbioe.2022.1071472] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 11/17/2022] [Indexed: 09/29/2023] Open
Abstract
Objectives: Stem cell-based tissue engineering approaches are promising for bone repair and regeneration. Periodontal ligament stem cells (PDLSCs) are a promising cell source for tissue engineering, especially for maxillofacial bone and periodontal regeneration. Many studies have shown potent results via PDLSCs in bone regeneration. In this review, we describe recent cutting-edge researches on PDLSC-based bone regeneration and periodontal tissue regeneration. Data and sources: An extensive search of the literature for papers related to PDLSCs-based bioactive constructs for bone tissue engineering was made on the databases of PubMed, Medline and Google Scholar. The papers were selected by three independent calibrated reviewers. Results: Multiple types of materials and scaffolds have been combined with PDLSCs, involving xeno genic bone graft, calcium phosphate materials and polymers. These PDLSC-based constructs exhibit the potential for bone and periodontal tissue regeneration. In addition, various osteo inductive agents and strategies have been applied with PDLSCs, including drugs, biologics, gene therapy, physical stimulation, scaffold modification, cell sheets and co-culture. Conclusoin: This review article demonstrates the great potential of PDLSCs-based bioactive constructs as a promising approach for bone and periodontal tissue regeneration.
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Affiliation(s)
- Zeqing Zhao
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
| | - Jin Liu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, China
| | - Michael D. Weir
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
| | - Abraham Schneider
- Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States
| | - Tao Ma
- Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States
| | - Thomas W. Oates
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
| | - Hockin H. K. Xu
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
- Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, United States
- Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Ke Zhang
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
| | - Yuxing Bai
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
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Paeoniflorin drives the immunomodulatory effects of mesenchymal stem cells by regulating Th1/Th2 cytokines in oral lichen planus. Sci Rep 2022; 12:18678. [PMID: 36333421 PMCID: PMC9636377 DOI: 10.1038/s41598-022-23158-0] [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: 04/29/2022] [Accepted: 10/25/2022] [Indexed: 11/06/2022] Open
Abstract
Lichen planus (LP) is a chronic inflammatory disease. Oral lichen planus (OLP) mainly appears as oral mucosal reticular or ulcerative lesions with an unknown etiology. We aimed to explore the immunomodulatory effect of paeoniflorin (PF) in mesenchymal stem cells (MSCs) and the potential involvement of Th1/Th2 cytokines in OLP. The effects of paeoniflorin on the proliferation and migration of MSCs were detected by Cell Counting Kit-8 (CCK8) and Transwell assays. MSCs were subjected to osteogenic, adipogenic and neurogenic induction followed by Alizarin red, oil red O, real-time PCR and immunofluorescence assays. We found that paeoniflorin promoted the proliferation, migration and multilineage differentiation of MSCs from OLP lesions (OLP-MSCs) in vitro. Paeoniflorin pretreatment increased the inhibitory effect of OLP-MSCs on peripheral blood mononuclear cells. Furthermore, paeoniflorin-pretreated OLP-MSCs simultaneously decreased Th1 cytokine levels and increased Th2 cytokine levels in T lymphocyte cocultures. Finally, paeoniflorin-pretreated OLP-MSCs also promoted the Th1/Th2 balance both in vitro and in the serum of mice that received skin allografts. In conclusion, paeoniflorin enhanced MSC immunomodulation and changed the inflammatory microenvironment via T lymphocytes, suggesting that the improvement of OLP-MSCs is a promising therapeutic approach for OLP.
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21
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Meng D, Wang Y, Liu T. Protective effects of silibinin on LPS-induced inflammation in human periodontal ligament cells. Front Chem 2022; 10:1019663. [PMID: 36300030 PMCID: PMC9591103 DOI: 10.3389/fchem.2022.1019663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 09/07/2022] [Indexed: 12/22/2023] Open
Abstract
Clinically, periodontitis is a chronic nonspecific inflammation that leads to damaged teeth and their supporting gum tissues. Although many studies on periodontitis have been conducted, therapy with natural products is still rare. Silibinin has been proven to have anti-inflammatory and antioxidant activities. However, the effects of silibinin on lipopolyssacharide (LPS)-induced inflammation in periodontal ligaments (PDLs) have not yet been investigated. In this study, the PDLs were treated with silibinin (10, 20, and 40 μM) in the presence of LPS. The results showed that silibinin treatment reduced the levels of NO, PGE2, IL-6, TNF-α, MMP-1, and MMP-3 and enhanced the activities of superoxide dismutase (SOD) and glutathione (GSH). Moreover, silibinin treatment downregulated RANKL levels and upregulated OPG and ALP levels. In summary, silibinin protected PDLs against LPS-induced inflammation, oxidative stress, and osteogenic differentiation.
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Affiliation(s)
- Di Meng
- Department of Stomatology, The Central Hospital Affilliated to Shandong First Medical University, Jinan, China
| | - Yuling Wang
- Department of Stomatology, The Central Hospital Affilliated to Shandong First Medical University, Jinan, China
- Department of Stomatology, Shandong Qianfoshan Hospital, Jinan, China
| | - Tongjun Liu
- Department of Stomatology, The Central Hospital Affilliated to Shandong First Medical University, Jinan, China
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22
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Dose-Dependent Effects of Melatonin on the Viability, Proliferation, and Differentiation of Dental Pulp Stem Cells (DPSCs). J Pers Med 2022; 12:jpm12101620. [PMID: 36294759 PMCID: PMC9605259 DOI: 10.3390/jpm12101620] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 09/20/2022] [Accepted: 09/21/2022] [Indexed: 11/09/2022] Open
Abstract
(1) Background: Dental pulp stem cells (DPSCs) are derived from pulp tissue lodged within human teeth and are mesenchymal in origin. These DPSCs have been demonstrated to dissociate into clusters of various cell lineages and are very easy to isolate, culture, and expand. Melatonin, a multifaceted molecule with a spectrum of effects in the human body, is known to influence stem cell viability, proliferation, and differentiation, but little is known about the impact melatonin has on the capacity of DPSCs to differentiate into adipocytes, osteocytes, and chondrocytes. The primary objective of this research was to explore the impact that melatonin has on proliferation, and the capacity of DPSCs to differentiate into adipocytes, osteocytes, and chondrocytes. (2) Methodology: DPSCs were extracted from 12 healthy human teeth, cultured, and expanded. Flow cytometry was performed to examine the surface stem cell markers. Further, melatonin was added to the cultured DPSCs in various concentrations, to assess cytotoxicity using an MTT assay. Following this, the DPSCs were tested for their proliferative ability, as well as adipogenic, osteogenic, and chondrogenic differentiation capabilities under the influence of variable concentrations of melatonin. (3) Results: DPSCs obtained from human teeth demonstrated surface characteristics of mesenchymal stem cells, as shown by the positive expression of CD105, CD90, and CD73 markers. An MTT cytotoxicity assay revealed that melatonin was well tolerated by the cells at low (1 µM) and high (25 µM) concentrations. Assessment of DPSC cell differentiation elucidated that melatonin at 1 µM and 25 µM concentrations with the induction media stimulated DPSCs to differentiate into osteocytes, but did not have much influence on adipogenic and chondrogenic differentiation. (4) Conclusions: Melatonin could be used in stem cell and tissue engineering applications for osteogenic differentiation of DPSCs and could protect these cells due to its cytoprotective, immunomodulatory, and antioxidant roles, in addition to being an osteopromoter molecule.
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23
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Mohd N, Razali M, Ghazali MJ, Abu Kasim NH. Current Advances of Three-Dimensional Bioprinting Application in Dentistry: A Scoping Review. MATERIALS (BASEL, SWITZERLAND) 2022; 15:6398. [PMID: 36143709 PMCID: PMC9504181 DOI: 10.3390/ma15186398] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 09/09/2022] [Accepted: 09/13/2022] [Indexed: 05/04/2023]
Abstract
Three-dimensional (3D) bioprinting technology has emerged as an ideal approach to address the challenges in regenerative dentistry by fabricating 3D tissue constructs with customized complex architecture. The dilemma with current dental treatments has led to the exploration of this technology in restoring and maintaining the function of teeth. This scoping review aims to explore 3D bioprinting technology together with the type of biomaterials and cells used for dental applications. Based on PRISMA-ScR guidelines, this systematic search was conducted by using the following databases: Ovid, PubMed, EBSCOhost and Web of Science. The inclusion criteria were (i) cell-laden 3D-bioprinted construct; (ii) intervention to regenerate dental tissue using bioink, which incorporates living cells or in combination with biomaterial; and (iii) 3D bioprinting for dental applications. A total of 31 studies were included in this review. The main 3D bioprinting technique was extrusion-based approach. Novel bioinks in use consist of different types of natural and synthetic polymers, decellularized extracellular matrix and spheroids with encapsulated mesenchymal stem cells, and have shown promising results for periodontal ligament, dentin, dental pulp and bone regeneration application. However, 3D bioprinting in dental applications, regrettably, is not yet close to being a clinical reality. Therefore, further research in fabricating ideal bioinks with implantation into larger animal models in the oral environment is very much needed for clinical translation.
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Affiliation(s)
- Nurulhuda Mohd
- Department of Restorative Dentistry, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia
| | - Masfueh Razali
- Department of Restorative Dentistry, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia
| | - Mariyam Jameelah Ghazali
- Department of Mechanical & Manufacturing Engineering, Faculty of Engineering & Built Environment, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia
| | - Noor Hayaty Abu Kasim
- DLima Dental Clinic, 44-A, Jalan Plumbum N7/N, Seksyen 7, Shah Alam 40000, Selangor, Malaysia
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24
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Wu M, Liu F, Yan L, Huang R, Hu R, Zhu J, Li S, Long C. MiR-145-5p restrains chondrogenic differentiation of synovium-derived mesenchymal stem cells by suppressing TLR4. NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS 2022; 41:625-642. [PMID: 35403567 DOI: 10.1080/15257770.2022.2057535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Osteoarthritis (OA) is a progressive degeneration of articular cartilage with involvement of synovial membrane, and subchondral bone. Recently, cell-based therapies, including the application of stem cells such as mesenchymal stem cells (MSCs), have been introduced for restoration of the articular cartilage. Toll-like receptors (TLRs) were reported to participate in OA progression and MSC chondrogenesis. Here, the role and molecular mechanism of toll like receptor 4 (TLR4) in chondrogenic differentiation of synovium-derived MSCs (SMSCs) were investigated. Molecular markers (CD44, CD90, CD45 and CD14) on SMSC surfaces were identified by flow cytometry. Multi-potential differentiation capacities of SMSCs for chondrogenesis, adipogenesis and osteogenesis were examined by Alcian blue, oil red O and Alizarin red staining, respectively. TLR4 and miR-145-5p levels in SMSCs were assessed using RT-qPCR. The protein expression of TGFB3, Col II, SOX9 and Aggrecan in SMSCs was tested by western blotting. Cytokine secretions were analyzed with ELISA for IL-1β and IL-6. Intracellular NAD+ content and NAD+/NADH ratio were assessed. The interaction between miR-145-5p and TLR4 was confirmed by RNA pulldown and luciferase reporter assays. In this study, SMSCs were identified to have immunophenotypic characteristics of MSCs. TLR4 knockdown inhibited chondrogenic and osteogenic differentiation of SMSCs. Mechanistically, TLR4 was targeted by miR-145-5p in SMSCs. Moreover, TLR4 elevation offset the inhibitory impact of miR-145-5p upregulation on chondrogenic differentiation of SMSCs. Overall, miR-145-5p restrains chondrogenesis of SMSCs by suppressing TLR4.
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Affiliation(s)
- Mingzheng Wu
- Department of Orthopedics, Wuhan Fourth Hospital (Wuhan Puai Hospital), Wuhan, Hubei, China
| | - Feng Liu
- Department of Orthopedics, Wuhan Fourth Hospital (Wuhan Puai Hospital), Wuhan, Hubei, China
| | - Li Yan
- Department of Orthopedics, Wuhan Fourth Hospital (Wuhan Puai Hospital), Wuhan, Hubei, China
| | - Ruokun Huang
- Department of Orthopedics, Wuhan Fourth Hospital (Wuhan Puai Hospital), Wuhan, Hubei, China
| | - Rui Hu
- Department of Orthopedics, Wuhan Fourth Hospital (Wuhan Puai Hospital), Wuhan, Hubei, China
| | - Jin Zhu
- Department of Orthopedics, Wuhan Fourth Hospital (Wuhan Puai Hospital), Wuhan, Hubei, China
| | - Shanqing Li
- Department of Orthopedics, Wuhan Fourth Hospital (Wuhan Puai Hospital), Wuhan, Hubei, China
| | - Chao Long
- Department of Radiology, Wuhan Fourth Hospital (Wuhan Puai Hospital), Wuhan, Hubei, China
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25
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Yang T, Tang S, Peng S, Ding G. The Effects of Mesenchymal Stem Cells on Oral Cancer and Possible Therapy Regime. Front Genet 2022; 13:949770. [PMID: 35846142 PMCID: PMC9280436 DOI: 10.3389/fgene.2022.949770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Accepted: 06/10/2022] [Indexed: 11/13/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are characterized by self-renewal, rapid proliferation, multipotent differentiation, and low immunogenicity. In addition, the tropism of MSCs towards injured tissues and tumor lesions makes them attractive candidates as cell carriers for therapeutic agent delivery and genetic material transfer. The interaction between tumor cells and MSCs in the tumor microenvironment plays an important role in tumor progression. Oral cancer is one of the most common malignant diseases in the head and neck. Although considerable improvements in the treatment of oral cancer were achieved, more effective and safer novel agents and treatments are still needed, and deeper studies on the etiology, pathology, and treatment of the oral cancer are desirable. In the past decades, many studies have reported the beneficial effects of MSCs-based therapies in the treatment of various diseases, including oral cancers. Meanwhile, other studies demonstrated that MSCs may enhance the growth and metastasis of oral cancer. In this paper, we reviewed the research progress of the effects of MSCs on oral cancers, the underlying mechanisms, and their potential applications in the treatment of oral cancers.
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26
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Zhang W, Yuan X. MicroRNA-20a elevates osteogenic/odontoblastic differentiation potential of dental pulp stem cells by nuclear factor-κB/p65 signaling pathway via targeting interleukin-8. Arch Oral Biol 2022; 138:105414. [DOI: 10.1016/j.archoralbio.2022.105414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 03/21/2022] [Accepted: 03/21/2022] [Indexed: 11/26/2022]
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Campbell TM, Dilworth FJ, Allan DS, Trudel G. The Hunt Is On! In Pursuit of the Ideal Stem Cell Population for Cartilage Regeneration. Front Bioeng Biotechnol 2022; 10:866148. [PMID: 35711627 PMCID: PMC9196866 DOI: 10.3389/fbioe.2022.866148] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Accepted: 04/27/2022] [Indexed: 01/15/2023] Open
Abstract
Cartilage injury and degeneration are hallmarks of osteoarthritis (OA), the most common joint disease. OA is a major contributor to pain, loss of function, and reduced quality of life. Over the last decade, considerable research efforts have focused on cell-based therapies, including several stem cell-derived approaches to reverse the cartilage alterations associated with OA. Although several tissue sources for deriving cell-based therapies have been identified, none of the resident stem cell populations have adequately fulfilled the promise of curing OA. Indeed, many cell products do not contain true stem cells. As well, issues with aggressive marketing efforts, combined with a lack of evidence regarding efficacy, lead the several national regulatory bodies to discontinue the use of stem cell therapy for OA until more robust evidence becomes available. A review of the evidence is timely to address the status of cell-based cartilage regeneration. The promise of stem cell therapy is not new and has been used successfully to treat non-arthritic diseases, such as hematopoietic and muscle disorders. These fields of regenerative therapy have the advantage of a considerable foundation of knowledge in the area of stem cell repair mechanisms, the role of the stem cell niche, and niche-supporting cells. This foundation is lacking in the field of cartilage repair. So, where should we look for the ideal stem cell to regenerate cartilage? It has recently been discovered that cartilage itself may contain a population of SC-like progenitors. Other potential tissues include stem cell-rich dental pulp and the adolescent growth plate, the latter of which contains chondrocyte progenitors essential for producing the cartilage scaffold needed for bone growth. In this article, we review the progress on stem cell therapies for arthritic disorders, focusing on the various stem cell populations previously used for cartilage regeneration, successful cases of stem cell therapies in muscle and hemopoietic disorders, some of the reasons why these other fields have been successful (i.e., "lessons learned" to be applied to OA stem cell therapy), and finally, novel potential sources of stem cells for regenerating damaged cartilage in vivo.
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Affiliation(s)
- T Mark Campbell
- Elisabeth Bruyère Hospital, Ottawa, ON, Canada
- Bone and Joint Research Laboratory, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - F Jeffrey Dilworth
- Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - David S Allan
- Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada
| | - Guy Trudel
- Bone and Joint Research Laboratory, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada
- Department of Biochemistry, Immunology and Microbiology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
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Enamel Matrix Derivative Enhances the Odontoblastic Differentiation of Dental Pulp Stem Cells via Activating MAPK Signaling Pathways. Stem Cells Int 2022; 2022:2236250. [PMID: 35530415 PMCID: PMC9071913 DOI: 10.1155/2022/2236250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 03/27/2022] [Accepted: 04/05/2022] [Indexed: 12/03/2022] Open
Abstract
The odontoblastic differentiation of dental pulp stem cells (DPSCs) contributes to pulp-dentin regeneration. Enamel matrix derivative (EMD) is considered to be a critical epithelial signal to induce cell differentiation during odontogenesis and has been widely applied to clinical periodontal tissue regeneration. The purpose of this study was to explore the effect of EMD on DPSCs proliferation and odontoblastic differentiation, as well as the underlying mechanisms. We conducted in vitro and in vivo researches to get a comprehensive understanding of EMD. In vitro phase: cell proliferation was assessed by a cell counting kit-8 (CCK-8) assay; then, alkaline phosphatase (ALP) activity and staining, alizarin red staining, real-time RT-PCR, and western blot analysis were conducted to determine the odontoblastic potential and involvement of MAPK signaling pathways. In vivo phase: after ensuring the biocompatibility of VitroGel 3D-RGD via scanning electron microscopy (SEM), the hydrogel mixture was subcutaneously injected into nude mice followed by histological and immunohistochemical analyses. The results revealed that EMD did not interfere with DPSCs proliferation but promoted the odontoblastic differentiation of DPSCs in vitro and in vivo. Furthermore, blocking the MAPK pathways suppressed the EMD-enhanced differentiation of DPSCs. Finally, VitroGel 3D-RGD could well support the proliferation, differentiation, and regeneration of DPSCs. Overall, this study demonstrates that EMD enhances the odontoblastic differentiation of DPSCs through triggering MAPK signaling pathways. The findings provide a new insight into the mechanism by which EMD affects DPSCs differentiation and proposes EMD as a promising candidate for future stem cell therapy in endodontics.
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29
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Lan C, Chen S, Jiang S, Lei H, Cai Z, Huang X. Different expression patterns of inflammatory cytokines induced by lipopolysaccharides from Escherichia coli or Porphyromonas gingivalis in human dental pulp stem cells. BMC Oral Health 2022; 22:121. [PMID: 35413908 PMCID: PMC9004173 DOI: 10.1186/s12903-022-02161-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 04/07/2022] [Indexed: 12/19/2022] Open
Abstract
Background Lipopolysaccharide (LPS) is one of the leading causes of pulpitis. The differences in establishing an in vitro pulpitis model by using different lipopolysaccharides (LPSs) are unknown. This study aimed to determine the discrepancy in the ability to induce the expression of inflammatory cytokines and the underlying mechanism between Escherichia coli (E. coli) and Porphyromonas gingivalis (P. gingivalis) LPSs in human dental pulp stem cells (hDPSCs).
Material and methods Quantitative real-time polymerase chain reaction (QRT-PCR) was used to evaluate the mRNA levels of inflammatory cytokines including IL-6, IL-8, COX-2, IL-1β, and TNF-α expressed by hDPSCs at each time point. ELISA was used to assess the interleukin-6 (IL-6) protein level. The role of toll-like receptors (TLR)2 and TLR4 in the inflammatory response in hDPSCs initiated by LPSs was assessed by QRT-PCR and flow cytometry. Results The E. coli LPS significantly enhanced the mRNA expression of inflammatory cytokines and the production of the IL-6 protein (p < 0.05) in hDPSCs. The peaks of all observed inflammation mediators’ expression in hDPSCs were reached 3–12 h after stimulation by 1 μg/mL E. coli LPS. E. coli LPS enhanced the TLR4 expression (p < 0.05) but not TLR2 in hDPSCs, whereas P. gingivalis LPS did not affect TLR2 or TLR4 expression in hDPSCs. The TLR4 inhibitor pretreatment significantly inhibited the gene expression of inflammatory cytokines upregulated by E. coli LPS (p < 0.05). Conclusion Under the condition of this study, E. coli LPS but not P. gingivalis LPS is effective in promoting the expression of inflammatory cytokines by hDPSCs. E. coli LPS increases the TLR4 expression in hDPSCs. P. gingivalis LPS has no effect on TLR2 or TLR4 expression in hDPSCs. Supplementary Information The online version contains supplementary material available at 10.1186/s12903-022-02161-x.
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Affiliation(s)
- Chunhua Lan
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou, 350002, China.,Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Shuai Chen
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou, 350002, China.,Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Shan Jiang
- Southern Medical University, Shenzhen Stomatology Hospital (Pingshan), Shenzhen, China
| | - Huaxiang Lei
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou, 350002, China.,Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Zhiyu Cai
- Department of Stomatology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Xiaojing Huang
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou, 350002, China. .,Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.
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Fraser D, Caton J, Benoit DSW. Periodontal Wound Healing and Regeneration: Insights for Engineering New Therapeutic Approaches. FRONTIERS IN DENTAL MEDICINE 2022. [DOI: 10.3389/fdmed.2022.815810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Periodontitis is a widespread inflammatory disease that leads to loss of the tooth supporting periodontal tissues. The few therapies available to regenerate periodontal tissues have high costs and inherent limitations, inspiring the development of new approaches. Studies have shown that periodontal tissues have an inherent capacity for regeneration, driven by multipotent cells residing in the periodontal ligament (PDL). The purpose of this review is to describe the current understanding of the mechanisms driving periodontal wound healing and regeneration that can inform the development of new treatment approaches. The biologic basis underlying established therapies such as guided tissue regeneration (GTR) and growth factor delivery are reviewed, along with examples of biomaterials that have been engineered to improve the effectiveness of these approaches. Emerging therapies such as those targeting Wnt signaling, periodontal cell delivery or recruitment, and tissue engineered scaffolds are described in the context of periodontal wound healing, using key in vivo studies to illustrate the impact these approaches can have on the formation of new cementum, alveolar bone, and PDL. Finally, design principles for engineering new therapies are suggested which build on current knowledge of periodontal wound healing and regeneration.
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Liu Y, Fu D. lncRNA ZNF710-AS1 Acts as a ceRNA for miR-146a-5p and miR-146b-5p to Accelerate Osteogenic Differentiation of PDLSCs by Upregulating the BMP6/Smad1/5/9 Pathway. J HARD TISSUE BIOL 2022. [DOI: 10.2485/jhtb.31.231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Ying Liu
- Dentistry Department, Jiufeng Street Health Service Center of East Lake Gaoxin District
| | - Dongjie Fu
- Department of Stomatology, Renmin Hospital of Wuhan University
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Age of the donor affects the nature of in vitro cultured human dental pulp stem cells. Saudi Dent J 2021; 33:524-532. [PMID: 34803296 PMCID: PMC8589584 DOI: 10.1016/j.sdentj.2020.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 08/26/2020] [Accepted: 09/13/2020] [Indexed: 12/13/2022] Open
Abstract
Objectives The dental pulp stem cells (DPSCs) of six donors (three young donors aged < 19 years and three adult donors aged > 25 and < 30 years) were characterized for their stem cell marker expression and differentiation potential to study the effect of donor age on DPSCs in vitro. Methods DPSCs were cultured in αMEM supplemented with 20% fetal calf serum (conventional conditions) or on fibronectin-coated flasks with neurobasal medium supplemented with B27, bFGF and EGF (alternative conditions). DPSCs were characterized by immunofluorescence staining to detect the neural crest/mesenchymal stem cells markers P75 and CD146, respectively. The differentiation potential was tested by the induction of DPSCs into osteogenic, adipogenic and glial lineages and then by detecting the corresponding markers osteocalcin, lipidtox and S100ß, respectively. Results The DPSCs of the young donors expressed CD146 only under the conventional conditions and expressed P75 regardless of the culture conditions. However, the DPSCs of adult donors expressed CD146 only under the alternative conditions and expressed P75 only under conventional conditions. Only the DPSCs of the young donors differentiated into the glial linage. The DPSCs of the adult donors differentiated more efficiently into the adipogenic linage. Osteogenic differentiation was comparable. Conclusion Donor age affects the expression of stem cell markers and differentiation potential of DPSCs. Moreover, the effect of culture conditions on DPSCs is age dependent.
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Stem Cells and Their Derivatives-Implications for Alveolar Bone Regeneration: A Comprehensive Review. Int J Mol Sci 2021; 22:ijms222111746. [PMID: 34769175 PMCID: PMC8583713 DOI: 10.3390/ijms222111746] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 10/25/2021] [Accepted: 10/27/2021] [Indexed: 02/07/2023] Open
Abstract
Oral and craniofacial bone defects caused by congenital disease or trauma are widespread. In the case of severe alveolar bone defect, autologous bone grafting has been considered a “gold standard”; however, the procedure has several disadvantages, including limited supply, resorption, donor site morbidity, deformity, infection, and bone graft rejection. In the last few decades, bone tissue engineering combined with stem cell-based therapy may represent a possible alternative to current bone augmentation techniques. The number of studies investigating different cell-based bone tissue engineering methods to reconstruct alveolar bone damage is rapidly rising. As an interdisciplinary field, bone tissue engineering combines the use of osteogenic cells (stem cells/progenitor cells), bioactive molecules, and biocompatible scaffolds, whereas stem cells play a pivotal role. Therefore, our work highlights the osteogenic potential of various dental tissue-derived stem cells and induced pluripotent stem cells (iPSCs), the progress in differentiation techniques of iPSCs into osteoprogenitor cells, and the efforts that have been made to fabricate the most suitable and biocompatible scaffold material with osteoinductive properties for successful bone graft generation. Moreover, we discuss the application of stem cell-derived exosomes as a compelling new form of “stem-cell free” therapy.
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Effect of 1,25-Dihydroxyvitamin D3 on Stem Cells from Human Apical Papilla: Adhesion, Spreading, Proliferation, and Osteogenic Differentiation. BIOMED RESEARCH INTERNATIONAL 2021; 2021:1481215. [PMID: 34660780 PMCID: PMC8519691 DOI: 10.1155/2021/1481215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 09/11/2021] [Indexed: 11/17/2022]
Abstract
Currently, it still remains a difficult problem to treat apical insufficiency of young permanent teeth resulted from pulp necrosis or periapical periodontitis. Previous studies have demonstrated that the treatment of revascularization using stem cells from apical papilla (SCAPs) results in increased root length and thickness of traumatized immature teeth and necrotic pulp. In this study, we investigated the role of 1,25-dihydroxyvitamin D3 in regulating the adhesion, spreading, proliferation, and osteogenic differentiation of SCAP, laying the foundation for subsequent clinical drug development. The immature tooth samples were collected in clinical treatment. SCAPs with stable passage ability were isolated and cultured. The multidifferentiation potential was determined by directed induction culture, while the stem cell characteristics were identified by flow cytometry. There were three groups: group A—SCAPs general culture group; group B—SCAPs osteogenesis induction culture group; and group C—SCAPs osteogenesis induction culture+1,25-dihydroxyvitamin D3 group, and the groups were compared statistically. The proliferation of SCAPs in each groups was detected through CCK-8 assay. RT-qPCR was used to detect the transcription levels of Runx2, ALP, Col I, and OCN of SCAPs in each groups. Results exhibited that the isolated SCAPs had multidifferentiation potential and stem cell characteristics. After 24 h culturing, cells in group C spread better than those in groups A and B. The proliferation activity of SCAPs factored by CCK-8 ranked as group C > group B > group A, while the transcription levels of Runx2, ALP, Col I, and OCN leveled as group C > group B > group A. These results suggested that 1,25-dihydroxyvitamin D3 can significantly promote the adhesion, spreading, and proliferation of SACPs and improve the osteogenic differentiation of SCAPs by means of regulating upward the transcription level of osteogenic differentiation marker.
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Zhang N, Zhao L, Liu D, Hu C, Wang Y, He T, Bi Y, He Y. Characterization of Urine-Derived Stem Cells from Patients with End-Stage Liver Diseases and Application to Induced Acute and Chronic Liver Injury of Nude Mice Model. Stem Cells Dev 2021; 30:1126-1138. [PMID: 34549601 DOI: 10.1089/scd.2021.0137] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Urine-derived stem cells (USCs) are adult stem cells isolated from urine with strong proliferative ability and differentiation potentials. Cell transplantation of USCs could partly repair liver injury. It has been reported that the proliferative ability of bone mesenchymal stem cells in patients with chronic liver failure is significantly lower than in patients without liver disease. The aim of this study was therefore to evaluate the biological characteristics of USCs from end-stage liver disease patients (LD-USCs, USCs from patients with liver disease) compared with those from normal healthy individuals (N-USCs, USCs from normal individuals), with a view to determining whether autologous USCs can be applied to the treatment of liver disease. In this study USCs were isolated from urine samples of male patients with end-stage liver disease. Adherent USCs exhibit a spindle- or rice grain-like morphology, and express CD24, CD29, CD73, CD90, and CD146 surface markers, but not CD31, CD34, CD45, and CD105. We observed no differences in cell morphology or cell surface marker profile between LD-USCs and N-USCs. LD-USCs exhibited similar proliferative, colony-forming, apoptotic, and migratory abilities to N-USCs. Both USCs demonstrated similar capacities for osteogenic, adipogenic, and chondrogenic differentiation. When USCs were transplanted into CCl4 treatment-induced acute and chronic liver fibrosis mouse models, we observed a decrease in liver index, recovery of alanine aminotransferase and aspartate aminotransferase levels, alleviation of liver tissue injury, and dramatic improvement of liver tissue structure. USC transplantation can effectively recover liver function and improve liver tissue damage in acute or chronic liver injury mouse models. According to the results, we concluded that the biological characteristics of LD-USCs are not affected by basic liver disease. This study provides further evidence of the stem cell characteristics and liver repair function of LD-USCs, which may serve as a theoretical and experimental foundation for autologous USC transplantation technology in the treatment of liver failure and end-stage liver diseases.
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Affiliation(s)
- Nannan Zhang
- Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Li Zhao
- Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Daijiang Liu
- Department of Gastroenterology, Chongqing Emergency Medical Center, Chongqing, China
| | - Chaoqun Hu
- Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Yi Wang
- Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Tongchuan He
- Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois, USA
| | - Yang Bi
- Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Yun He
- Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
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Wu Z, Chen S, He Y, Zhang D, Zou S, Xie J, Zhou C. Connective tissue growth factor promotes cell-to-cell communication in human periodontal ligament stem cells via MAPK and PI3K pathway. J Periodontol 2021; 93:e60-e72. [PMID: 34532860 DOI: 10.1002/jper.21-0339] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 08/26/2021] [Accepted: 09/10/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Cell-cell communication is an essential process to respond to biological stimuli and sustain the micro environmental homeostasis of human periodontal ligament stem cells (hPDLSCs). Connective tissue growth factor (CTGF), a critical secreted matrix protein, exhibits significant tasks in regulating the cell-cell and cell-matrix interactions. This study aimed to explore the relationship between CTGF and cell communication and the underlying mechanism. METHODS qRT-PCR was used to detect CCN family, connexin, and pannexin family expression in hPDLSCs. Stimulation with CTGF, cell migration assay was performed to examine the wound repair. The scrape loading/dye transfer assay was employed to access lucifer Yellow molecules transfer efficiency mediated by cell-cell communication. Connexin43 (Cx43), Pannexin1 (Panx1), MAPK, and the PI3K/Akt signaling pathway proteins were examined via Western blotting. Immunofluorescence was applied to visualize the localization of specific proteins within cells. Corresponding pathway inhibitors were applied to hPDLSCs to detect Cx43, Panx1 expression, and intercellular communication induced by CTGF. RESULTS Our result showed that CTGF was the second most expressed CCN family member in hPDLSCs. Cx43, and Panx1 were the most widely expressed gap junction hemichannels in hPDLSCs. CTGF enhanced hPDLSCs migration in a dose-dependent manner. CTGF promoted cell-cell communication by up-regulating Cx43 and Panx1. CTGF induced Akt, JNK, and p38 phosphorylation and subcellular relocation. Inhibiting corresponding pathways reduced Cx43 expression, thereby weakening CTGF-induced cell-cell communication. However, the Panx1 expression in CTGF-treated hPDLSCs mainly depended on PI3K/Akt signaling. CONCLUSION We provided novel evidence that CTGF promoted cell-cell communication in hPDLSCs through MAPK and PI3K pathway.
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Affiliation(s)
- Zuping Wu
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Sirui Chen
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yuying He
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Demao Zhang
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Shujuan Zou
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jing Xie
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Chenchen Zhou
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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Mercado-Rubio MD, Pérez-Argueta E, Zepeda-Pedreguera A, Aguilar-Ayala FJ, Peñaloza-Cuevas R, Kú-González A, Rojas-Herrera RA, Rodas-Junco BA, Nic-Can GI. Similar Features, Different Behaviors: A Comparative In VitroStudy of the Adipogenic Potential of Stem Cells from Human Follicle, Dental Pulp, and Periodontal Ligament. J Pers Med 2021; 11:jpm11080738. [PMID: 34442382 PMCID: PMC8401480 DOI: 10.3390/jpm11080738] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 07/24/2021] [Accepted: 07/24/2021] [Indexed: 12/21/2022] Open
Abstract
Dental tissue-derived mesenchymal stem cells (DT-MSCs) are a promising resource for tissue regeneration due to their multilineage potential. Despite accumulating data regarding the biology and differentiation potential of DT-MSCs, few studies have investigated their adipogenic capacity. In this study, we have investigated the mesenchymal features of dental pulp stem cells (DPSCs), as well as the in vitro effects of different adipogenic media on these cells, and compared them to those of periodontal ligament stem cells (PLSCs) and dental follicle stem cells (DFSCs). DFSC, PLSCs, and DPSCs exhibit similar morphology and proliferation capacity, but they differ in their self-renewal ability and expression of stemness markers (e.g OCT4 and c-MYC). Interestingly, DFSCs and PLSCs exhibited more lipid accumulation than DPSCs when induced to adipogenic differentiation. In addition, the mRNA levels of adipogenic markers (PPAR, LPL, and ADIPOQ) were significantly higher in DFSCs and PLSCs than in DPSCs, which could be related to the differences in the adipogenic commitment in those cells. These findings reveal that the adipogenic capacity differ among DT-MSCs, features that might be advantageous to increasing our understanding about the developmental origins and regulation of adipogenic commitment.
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Affiliation(s)
- Melissa D. Mercado-Rubio
- Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Periférico Norte Kilómetro 33.5, Tablaje Catastral 13615, Chuburná de Hidalgo Inn, Mérida 97203, Yucatán, Mexico; (M.D.M.-R.); (E.P.-A.); (A.Z.-P.); (R.A.R.-H.)
| | - Erick Pérez-Argueta
- Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Periférico Norte Kilómetro 33.5, Tablaje Catastral 13615, Chuburná de Hidalgo Inn, Mérida 97203, Yucatán, Mexico; (M.D.M.-R.); (E.P.-A.); (A.Z.-P.); (R.A.R.-H.)
| | - Alejandro Zepeda-Pedreguera
- Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Periférico Norte Kilómetro 33.5, Tablaje Catastral 13615, Chuburná de Hidalgo Inn, Mérida 97203, Yucatán, Mexico; (M.D.M.-R.); (E.P.-A.); (A.Z.-P.); (R.A.R.-H.)
| | - Fernando J. Aguilar-Ayala
- Laboratorio Translacional de Células Troncales-Facultad de Odontología, Universidad Autónoma de Yucatán, Calle 61-A X Av. Itzaes Costado Sur “Parque de la Paz”, Col. Centro, Mérida 97000, Yucatán, Mexico; (F.J.A.-A.); (R.P.-C.)
| | - Ricardo Peñaloza-Cuevas
- Laboratorio Translacional de Células Troncales-Facultad de Odontología, Universidad Autónoma de Yucatán, Calle 61-A X Av. Itzaes Costado Sur “Parque de la Paz”, Col. Centro, Mérida 97000, Yucatán, Mexico; (F.J.A.-A.); (R.P.-C.)
| | - Angela Kú-González
- Unidad de Bioquímica y Biología Molecular de Plantas, Centro de Investigación Científica de Yucatán, Calle 43 No. 130, Col. Chuburná de Hidalgo, Mérida 97200, Yucatán, Mexico;
| | - Rafael A. Rojas-Herrera
- Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Periférico Norte Kilómetro 33.5, Tablaje Catastral 13615, Chuburná de Hidalgo Inn, Mérida 97203, Yucatán, Mexico; (M.D.M.-R.); (E.P.-A.); (A.Z.-P.); (R.A.R.-H.)
| | - Beatriz A. Rodas-Junco
- Laboratorio Translacional de Células Troncales-Facultad de Odontología, Universidad Autónoma de Yucatán, Calle 61-A X Av. Itzaes Costado Sur “Parque de la Paz”, Col. Centro, Mérida 97000, Yucatán, Mexico; (F.J.A.-A.); (R.P.-C.)
- CONACYT-Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Periférico Norte Kilómetro 33.5, Tablaje Catastral 13615, Chuburná de Hidalgo Inn, Mérida 97203, Yucatán, Mexico
- Correspondence: (B.A.R.-J.); or (G.I.N.-C.)
| | - Geovanny I. Nic-Can
- Laboratorio Translacional de Células Troncales-Facultad de Odontología, Universidad Autónoma de Yucatán, Calle 61-A X Av. Itzaes Costado Sur “Parque de la Paz”, Col. Centro, Mérida 97000, Yucatán, Mexico; (F.J.A.-A.); (R.P.-C.)
- CONACYT-Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Periférico Norte Kilómetro 33.5, Tablaje Catastral 13615, Chuburná de Hidalgo Inn, Mérida 97203, Yucatán, Mexico
- Correspondence: (B.A.R.-J.); or (G.I.N.-C.)
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Zhong J, Pierantoni M, Weinkamer R, Brumfeld V, Zheng K, Chen J, Swain MV, Weiner S, Li Q. Microstructural heterogeneity of the collagenous network in the loaded and unloaded periodontal ligament and its biomechanical implications. J Struct Biol 2021; 213:107772. [PMID: 34311076 DOI: 10.1016/j.jsb.2021.107772] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 07/02/2021] [Accepted: 07/19/2021] [Indexed: 01/17/2023]
Abstract
The periodontal ligament (PDL) is a highly heterogeneous fibrous connective tissue and plays a critical role in distributing occlusal forces and regulating tissue remodeling. Its mechanical properties are largely determined by the extracellular matrix, comprising a collagenous fiber network interacting with the capillary system as well as interstitial fluid containing proteoglycans. While the phase-contrast micro-CT technique has portrayed the 3D microscopic heterogeneity of PDL, the topological parameters of its network, which is crucial to understanding the multiscale constitutive behavior of this tissue, has not been characterized quantitatively. This study aimed to provide new understanding of such microscopic heterogeneity of the PDL with quantifications at both tissue and collagen network levels in a spatial manner, by combining phase-contrast micro-CT imaging and a purpose-built image processing algorithm for fiber analysis. Both variations within a PDL and among the PDL with different shapes, i.e. round-shaped and kidney-shaped PDLs, are described in terms of tissue thickness, fiber distribution, local fiber densities, and fiber orientation (namely azimuthal and elevation angles). Furthermore, the tissue and collagen fiber network responses to mechanical loading were evaluated in a similar manner. A 3D helical alignment pattern was observed in the fiber network, which appears to regulate and adapt a screw-like tooth motion under occlusion. The microstructural heterogeneity quantified here allows development of sample-specific constitutive models to characterize the PDL's functional and pathological loading responses, thereby providing a new multiscale framework for advancing our knowledge of this complex limited mobility soft-hard tissue interface.
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Affiliation(s)
- Jingxiao Zhong
- School of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, Sydney, Australia
| | - Maria Pierantoni
- Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel; Department of Biomedical Engineering, Lund University, Lund, Sweden
| | - Richard Weinkamer
- Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany
| | - Vlad Brumfeld
- Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel
| | - Keke Zheng
- School of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, Sydney, Australia; College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, UK
| | - Junning Chen
- College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, UK
| | - Michael V Swain
- School of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, Sydney, Australia
| | - Steve Weiner
- Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Qing Li
- School of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, Sydney, Australia.
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Shoushrah SH, Transfeld JL, Tonk CH, Büchner D, Witzleben S, Sieber MA, Schulze M, Tobiasch E. Sinking Our Teeth in Getting Dental Stem Cells to Clinics for Bone Regeneration. Int J Mol Sci 2021; 22:6387. [PMID: 34203719 PMCID: PMC8232184 DOI: 10.3390/ijms22126387] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/27/2021] [Accepted: 06/02/2021] [Indexed: 12/12/2022] Open
Abstract
Dental stem cells have been isolated from the medical waste of various dental tissues. They have been characterized by numerous markers, which are evaluated herein and differentiated into multiple cell types. They can also be used to generate cell lines and iPSCs for long-term in vitro research. Methods for utilizing these stem cells including cellular systems such as organoids or cell sheets, cell-free systems such as exosomes, and scaffold-based approaches with and without drug release concepts are reported in this review and presented with new pictures for clarification. These in vitro applications can be deployed in disease modeling and subsequent pharmaceutical research and also pave the way for tissue regeneration. The main focus herein is on the potential of dental stem cells for hard tissue regeneration, especially bone, by evaluating their potential for osteogenesis and angiogenesis, and the regulation of these two processes by growth factors and environmental stimulators. Current in vitro and in vivo publications show numerous benefits of using dental stem cells for research purposes and hard tissue regeneration. However, only a few clinical trials currently exist. The goal of this review is to pinpoint this imbalance and encourage scientists to pick up this research and proceed one step further to translation.
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Affiliation(s)
| | | | | | | | | | | | | | - Edda Tobiasch
- Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig- Strasse. 20, 53359 Rheinbach, Germany; (S.H.S.); (J.L.T.); (C.H.T.); (D.B.); (S.W.); (M.A.S.); (M.S.)
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Magalhães FD, Sarra G, Carvalho GL, Pedroni ACF, Marques MM, Chambrone L, Gimenez T, Moreira MS. Dental tissue-derived stem cell sheet biotechnology for periodontal tissue regeneration: A systematic review. Arch Oral Biol 2021; 129:105182. [PMID: 34098416 DOI: 10.1016/j.archoralbio.2021.105182] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 05/26/2021] [Accepted: 05/27/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE This study aimed to conduct a systematic review of the use of a cell sheet formed by mesenchymal stem cells derived from dental tissues (ddMSCs) for periodontal tissue regeneration in animal models in comparison with any other type of regenerative treatment. DESIGN PubMed and Scopus databases were searched for relevant studies up to December 2020. The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. RESULTS Of the 1542 potentially relevant articles initially identified, 33 fulfilled the eligibility criteria and were considered for this review. Even with a wide variety of selected study methods, the periodontal tissue was always regenerated; this indicates the potential for the use of these cell sheets in the future of periodontics. However, this regeneration process is not always complete. CONCLUSION Despite the implantation, ddMSCs sheets have a great potential to be used in the regeneration of periodontal tissue. More in vivo studies should be conducted using standardized techniques for cell sheet implantation to obtain more robust evidence of the relevance of using this modality of cell therapy for periodontal tissue regeneration.
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Affiliation(s)
- Fabiana Divina Magalhães
- Graduation Dentistry Program, Ibirapuera University, Av. Interlagos 1329 - 4º, Chácara Flora, São Paulo, SP, ZIP code: 04661-100, Brazil
| | - Giovanna Sarra
- Department of Restorative Dentistry, School of Dentistry, Universidade de São Paulo, Av. Prof. Lineu Prestes 2227, São Paulo, SP, ZIP code: 05508-000, Brazil
| | - Giovanna Lopes Carvalho
- A.C. Camargo Cancer Center, Stomatology Department, Rua Tamandaré 753, Liberdade, São Paulo, SP, Zip code: 01525-001, Brazil
| | - Ana Clara Fagundes Pedroni
- Graduation Dentistry Program, Ibirapuera University, Av. Interlagos 1329 - 4º, Chácara Flora, São Paulo, SP, ZIP code: 04661-100, Brazil
| | - Márcia Martins Marques
- Graduation Dentistry Program, Ibirapuera University, Av. Interlagos 1329 - 4º, Chácara Flora, São Paulo, SP, ZIP code: 04661-100, Brazil
| | - Leandro Chambrone
- Graduation Dentistry Program, Ibirapuera University, Av. Interlagos 1329 - 4º, Chácara Flora, São Paulo, SP, ZIP code: 04661-100, Brazil
| | - Thaís Gimenez
- Graduation Dentistry Program, Ibirapuera University, Av. Interlagos 1329 - 4º, Chácara Flora, São Paulo, SP, ZIP code: 04661-100, Brazil
| | - Maria Stella Moreira
- Graduation Dentistry Program, Ibirapuera University, Av. Interlagos 1329 - 4º, Chácara Flora, São Paulo, SP, ZIP code: 04661-100, Brazil; A.C. Camargo Cancer Center, Stomatology Department, Rua Tamandaré 753, Liberdade, São Paulo, SP, Zip code: 01525-001, Brazil.
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Characteristics, Classification, and Application of Stem Cells Derived from Human Teeth. Stem Cells Int 2021; 2021:8886854. [PMID: 34194509 PMCID: PMC8184333 DOI: 10.1155/2021/8886854] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 02/12/2021] [Accepted: 05/07/2021] [Indexed: 12/31/2022] Open
Abstract
Since mesenchymal stem cells derived from human teeth are characterized as having the properties of excellent proliferation, multilineage differentiation, and immune regulation. Dental stem cells exhibit fibroblast-like microscopic appearance and express mesenchymal markers, embryonic markers, and vascular markers but do not express hematopoietic markers. Dental stem cells are a mixed population with different sensitive markers, characteristics, and therapeutic effects. Single or combined surface markers are not only helpful for understanding the subpopulation of mixed stem cell populations according to cell function but also for improving the stable treatment effect of dental stem cells. Focusing on the discovery and characterization of stem cells isolated from human teeth over the past 20 years, this review outlines the effect of marker sorting on cell proliferation and differentiation ability and the assessment of the clinical application potential. Classified dental stem cells from markers and functional molecules can solve the problem of heterogeneity and ensure the efficacy of cell therapy strategies including dentistry, neurologic diseases, bone repair, and tissue engineering.
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Meng H, Hu L, Zhou Y, Ge Z, Wang H, Wu CT, Jin J. A Sandwich Structure of Human Dental Pulp Stem Cell Sheet, Treated Dentin Matrix, and Matrigel for Tooth Root Regeneration. Stem Cells Dev 2021; 29:521-532. [PMID: 32089088 DOI: 10.1089/scd.2019.0162] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Tooth loss can cause a lot of physiological and psychological suffering. And tooth root engineering is a promising way for tooth loss treatment. Two kinds of seed cells are usually adopted for tooth root regeneration. In this study, a practical sandwich structure for tooth root regeneration was developed, which was constituted by only one kind of seed cell: human dental pulp stem cells (hDPSCs) and three kinds of graft materials: Vitamin C (VC) induced hDPSC sheet, human treated dentin matrix (hTDM), and Matrigel. It was found that VC could induce hDPSCs to form a cell sheet with two or three cell layers and promote their collagen type I (COL1) mRNA expression obviously. hDPSCs could attach and grow on hTDM, and the mRNA expression of osteocalcin (OCN), dentin sialophosphoprotein (DSPP), vascular endothelial growth factor receptor 1 (VEGFR1), and Nestin in hDPSCs was obviously upregulated by hTDM leaching solution. hDPSCs could stretch and proliferate in Matrigel. And when cultured in Matrigel condition medium, they positively expressed CD31, β3-Tubulin, and Nestin proteins, as well as increased the mRNA expression of OCN, ALP, and Nestin. Furthermore, periodontium, dentin, and pulp-like tissues were successfully regenerated after the sandwich structure of hDPSC sheet/TDM/Matrigel was transplanted in nude mice subcutaneously for 3 months. Periodontium-like dense connective tissue was regenerated around the hTDM, and a great mass of predentin was formed on the cavity side of hTDM. Odontoblast-like cells and blood vessel-like structures, even nerve-like fibers, were observed in the pulp cavity. In summary, the above results showed that hDPSCs could be used as seed cells for the whole tooth root regeneration, and the sandwich structure constituted by hDPSC sheet, TDM/hDPSCs, and Matrigel/hDPSCs could be utilized for tooth root regeneration.
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Affiliation(s)
- Hongfang Meng
- School of Chemical Engineering and Technology, Tianjin University, Tianjin, People's Republic of China.,Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China
| | - Lei Hu
- Molecular Laboratory for Gene Therapy and Tooth Regeneration, Capital Medical University School of Stomatology, Beijing, People's Republic of China
| | - Ying Zhou
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China
| | - Zhiqiang Ge
- School of Chemical Engineering and Technology, Tianjin University, Tianjin, People's Republic of China
| | - Hua Wang
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China
| | - Chu-Tse Wu
- School of Chemical Engineering and Technology, Tianjin University, Tianjin, People's Republic of China.,Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China
| | - Jide Jin
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China
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Pagella P, de Vargas Roditi L, Stadlinger B, Moor AE, Mitsiadis TA. A single-cell atlas of human teeth. iScience 2021; 24:102405. [PMID: 33997688 PMCID: PMC8099559 DOI: 10.1016/j.isci.2021.102405] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/29/2021] [Accepted: 04/06/2021] [Indexed: 12/31/2022] Open
Abstract
Teeth exert fundamental functions related to mastication and speech. Despite their great biomedical importance, an overall picture of their cellular and molecular composition is still missing. In this study, we have mapped the transcriptional landscape of the various cell populations that compose human teeth at single-cell resolution, and we analyzed in deeper detail their stem cell populations and their microenvironment. Our study identified great cellular heterogeneity in the dental pulp and the periodontium. Unexpectedly, we found that the molecular signatures of the stem cell populations were very similar, while their respective microenvironments strongly diverged. Our findings suggest that the microenvironmental specificity is a potential source for functional differences between highly similar stem cells located in the various tooth compartments and open new perspectives toward cell-based dental therapeutic approaches.
Dental atlas of the pulp and periodontal tissues of human teeth Identification of three common MSC subclusters between dental pulp and periodontium Dental pulp and periodontal MSCs are similar, and their niches diverge
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Affiliation(s)
- Pierfrancesco Pagella
- Orofacial Development and Regeneration, Faculty of Medicine, Institute of Oral Biology, Center of Dental Medicine, University of Zurich, Plattenstrasse 11, 8032 Zurich, Switzerland
| | | | - Bernd Stadlinger
- Clinic of Cranio-Maxillofacial and Oral Surgery, University of Zurich, Zurich, Switzerland
| | - Andreas E. Moor
- Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
- Corresponding author
| | - Thimios A. Mitsiadis
- Orofacial Development and Regeneration, Faculty of Medicine, Institute of Oral Biology, Center of Dental Medicine, University of Zurich, Plattenstrasse 11, 8032 Zurich, Switzerland
- Corresponding author
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44
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Zhao Y, Xie L. An Update on Mesenchymal Stem Cell-Centered Therapies in Temporomandibular Joint Osteoarthritis. Stem Cells Int 2021; 2021:6619527. [PMID: 33868408 PMCID: PMC8035039 DOI: 10.1155/2021/6619527] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 02/20/2021] [Accepted: 03/19/2021] [Indexed: 02/05/2023] Open
Abstract
Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by cartilage degeneration, disrupted subchondral bone remodeling, and synovitis, seriously affecting the quality of life of patients with chronic pain and functional disabilities. Current treatments for TMJOA are mainly symptomatic therapies without reliable long-term efficacy, due to the limited self-renewal capability of the condyle and the poorly elucidated pathogenesis of TMJOA. Recently, there has been increased interest in cellular therapies for osteoarthritis and TMJ regeneration. Mesenchymal stem cells (MSCs), self-renewing and multipotent progenitor cells, play a promising role in TMJOA treatment. Derived from a variety of tissues, MSCs exert therapeutic effects through diverse mechanisms, including chondrogenic differentiation; fibrocartilage regeneration; and trophic, immunomodulatory, and anti-inflammatory effects. Here, we provide an overview of the therapeutic roles of various tissue-specific MSCs in osteoarthritic TMJ or TMJ regenerative tissue engineering, with an additional focus on joint-resident stem cells and other cellular therapies, such as exosomes and adipose-derived stromal vascular fraction (SVF). Additionally, we summarized the updated pathogenesis of TMJOA to provide a better understanding of the pathological mechanisms of cellular therapies. Although limitations exist, MSC-centered therapies still provide novel, innovative approaches for TMJOA treatment.
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Affiliation(s)
- Yifan Zhao
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Liang Xie
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
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45
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Modulation of the Dental Pulp Stem Cell Secretory Profile by Hypoxia Induction Using Cobalt Chloride. J Pers Med 2021; 11:jpm11040247. [PMID: 33808091 PMCID: PMC8066657 DOI: 10.3390/jpm11040247] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 03/19/2021] [Accepted: 03/23/2021] [Indexed: 12/15/2022] Open
Abstract
The action of stem cells is mediated by their paracrine secretions which comprise the secretory profile. Various approaches can be used to modify the secretory profile of stem cells. Creating a hypoxic environment is one method. The present study aims to demonstrate the influence of CoCl2 in generating hypoxic conditions in a dental pulp stem cell (DPSCs) culture, and the effect of this environment on their secretory profile. DPSCs that were isolated from human permanent teeth were characterized and treated with different concentrations of CoCl2 to assess their viability by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and proliferation by a cell counting kit (CCK)-8 assay. The gene expression level of hypoxia-inducible factor 1-alpha (HIF-1α) was analyzed by quantitative real time polymerase chain reaction (qRT-PCR) to demonstrate a hypoxic environment. Comparative evaluation of the growth factors and cytokines were done by cytometric bead array. Gene expression levels of transcription factors OCT4 and SOX2 were analyzed by qRT-PCR to understand the effect of CoCl2 on stemness in DPSCs. DPSCs were positive for MSC-specific markers. Doses of CoCl2, up to 20 µM, did not negatively affect cell viability; in low doses (5 µM), it promoted cell survival. Treatment with 10 µM of CoCl2 significantly augmented the genetic expression of HIF-1α. Cells treated with 10 µM of CoCl2 showed changes in the levels of growth factors and cytokines produced. It was very evident that CoCl2 also increased the expression of OCT4 and SOX2, which is the modulation of stemness of DPSCs. A CoCl2 treatment-induced hypoxic environment modulates the secretory profile of DPSCs.
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Regulatory Effect of Mesenchymal Stem Cells on T Cell Phenotypes in Autoimmune Diseases. Stem Cells Int 2021; 2021:5583994. [PMID: 33859701 PMCID: PMC8024100 DOI: 10.1155/2021/5583994] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/03/2021] [Accepted: 03/11/2021] [Indexed: 02/08/2023] Open
Abstract
Research on mesenchymal stem cells (MSCs) starts from the earliest assumption that cells derived from the bone marrow have the ability to repair tissues. Several scientists have since documented the crucial role of bone marrow-derived MSCs (BM-MSCs) in processes such as embryonic bone and cartilage formation, adult fracture and tissue repair, and immunomodulatory activities in therapeutic applications. In addition to BM-MSCs, several sources of MSCs have been reported to possess tissue repair and immunoregulatory abilities, making them potential treatment options for many diseases. Therefore, the therapeutic potential of MSCs in various diseases including autoimmune conditions has been explored. In addition to an imbalance of T cell subsets in most patients with autoimmune diseases, they also exhibit complex disease manifestations, overlapping symptoms among diseases, and difficult treatment. MSCs can regulate T cell subsets to restore their immune homeostasis toward disease resolution in autoimmune conditions. This review summarizes the role of MSCs in relieving autoimmune diseases via the regulation of T cell phenotypes.
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47
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Stem Cell-based Dental Pulp Regeneration: Insights From Signaling Pathways. Stem Cell Rev Rep 2021; 17:1251-1263. [PMID: 33459973 DOI: 10.1007/s12015-020-10117-3] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/29/2020] [Indexed: 02/05/2023]
Abstract
Deep caries, trauma, and severe periodontitis result in pulpitis, pulp necrosis, and eventually pulp loss. However, no clinical therapy can regenerate lost pulp. A novel pulp regeneration strategy for clinical application is urgently needed. Signaling transduction plays an essential role in regulating the regenerative potentials of dental stem cells. Cytokines or growth factors, such as stromal cell-derived factor (SDF), fibroblast growth factor (FGF), bone morphogenetic protein (BMP), vascular endothelial growth factor (VEGF), WNT, can promote the migration, proliferation, odontogenic differentiation, pro-angiogenesis, and pro-neurogenesis potentials of dental stem cells respectively. Using the methods of signaling modulation including growth factors delivery, genetic modification, and physical stimulation has been applied in multiple preclinical studies of pulp regeneration based on cell transplantation or cell homing. Transplanting dental stem cells and growth factors encapsulated into scaffold regenerated vascularized pulp-like tissue in the root canal. Also, injecting a flowable scaffold only with chemokines recruited endogenous stem/progenitor cells for pulp regeneration. Notably, dental pulp regeneration has gradually developed into the clinical phase. These findings enlightened us on a novel strategy for structural and functional pulp regeneration through elaborate modulation of signaling transduction spatially and temporally via clinically applicable growth factors delivery. But challenges, such as the adverse effects of unphysiological signaling activation, the controlled drug release system, and the safety of gene modulation, are necessary to be tested in future works for promoting the clinical translation of pulp regeneration.
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48
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Li N, Zhang Y, Nepal N, Li G, Yang N, Chen H, Lin Q, Ji X, Zhang S, Jin S. Dental pulp stem cells overexpressing hepatocyte growth factor facilitate the repair of DSS-induced ulcerative colitis. Stem Cell Res Ther 2021; 12:30. [PMID: 33413675 PMCID: PMC7792189 DOI: 10.1186/s13287-020-02098-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 12/10/2020] [Indexed: 12/21/2022] Open
Abstract
Background Ulcerative colitis (UC) is a chronic and recurrent disease without satisfactory treatment strategies. Dental pulp stem cell (DPSC) transplantation has been proposed as a potential therapy for UC. This study aimed to investigate the therapeutic effects of the rat hepatocyte growth factor (HGF) gene transduced into DPSCs for UC. Methods The therapeutic effects of HGF-DPSCs transplanted intravenously into a rat model of UC induced by 5% dextran sulphate sodium (DSS) were compared with the other treatment groups (LV-HGF group, DPSCs group and GFP-DPSCs group). Immunofluorescence and immunohistochemistry were used to observe the localization and proliferation of HGF-DPSCs at the site of colon injury. The expression levels of inflammatory factors were detected by real-time quantitative PCR (RT-PCR) and western blotting. The oxidative stress markers were detected by ELISA. DAI scores and body weight changes were used to macroscopically evaluate the treatment of rats in each group. Results Immunofluorescence and immunohistochemistry assays showed that HGF-DPSCs homed to colon injury sites and colocalized with intestinal stem cell (ISC) markers (Bmi1, Musashi1 and Sox9) and significantly promoted protein expression (Bmi1, Musashi1, Sox9 and PCNA). Anti-inflammatory cytokine (TGF-β and IL-10) expression was the highest in the HGF-DPSCs group compared with the other treatment groups, while the expression of pro-inflammatory cytokines (TNF-α and INF-γ) was the lowest. Additionally, the oxidative stress response results showed that malondialdehyde (MDA) and myeloperoxidase (MPO) expression decreased while superoxide dismutase (SOD) expression increased, especially in the HGF-DPSCs group. The DAI scores showed a downward trend with time in the five treatment groups, whereas body weight increased, and the changes were most prominent in the HGF-DPSCs group. Conclusions The study indicated that HGF-DPSCs can alleviate injuries to the intestinal mucosa by transdifferentiating into ISC-like cells, promoting ISC-like cell proliferation, suppressing inflammatory responses and reducing oxidative stress damage, which provides new ideas for the clinical treatment of UC.
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Affiliation(s)
- Ning Li
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Yichi Zhang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Narayan Nepal
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Guoqing Li
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Ningning Yang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Haoyuan Chen
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Qiuchi Lin
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Xuechun Ji
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Sijia Zhang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Shizhu Jin
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China.
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Xu L, Sun X, Zhu G, Mao J, Baban B, Qin X. Local delivery of simvastatin maintains tooth anchorage during mechanical tooth moving via anti-inflammation property and AMPK/MAPK/NF-kB inhibition. J Cell Mol Med 2020; 25:333-344. [PMID: 33314684 PMCID: PMC7810950 DOI: 10.1111/jcmm.16058] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Accepted: 10/11/2020] [Indexed: 12/13/2022] Open
Abstract
Simvastatin (SMV) could increase tooth anchorage during orthodontic tooth movement (OTM). However, previous studies on its bone‐specific anabolic and anti‐inflammation properties were based on static in vitro and in vivo conditions. AMPK is a stress‐activated kinase that protects tissue against serious damage from overloading inflammation. Rat periodontal ligament cells (PDLCs) were subjected to a serial of SMV concentrations to investigate the optimization that promoted osteogenic differentiation. The PDLCs in static and/or tensile culturing conditions then received the proper concentration SMV. Related factors expression was measured by the protein array, real‐time PCR and Western blot. The 0.05UM SMV triggered osteogenic differentiation of PDLCs. The inhibition of AMPK activation through a pharmacological approach (Compound C) caused dramatic decrease in osteogenic/angiogenic gene expression and significant increase in inflammatory NF‐κB phosphorylation. In contrast, pharmacological activation of AMPK by AICAR significantly inhibited inflammatory factors expression and activated ERK1/2, P38 MAPK phosphorylation. Moreover, AMPK activation induced by SMV delivery significantly attenuated the osteoclastogenesis and decreased the expression of pro‐inflammatory TNF‐α and NF‐κB in a rodent model of OTM. The current studies suggested that SMV could intrigue intrinsic activation of AMPK in PDLCs that promote attenuate the inflammation which occurred under tensile irritation through AMPK/MAPK/NF‐kB Inhibition.
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Affiliation(s)
- Lianyi Xu
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaojuan Sun
- Department of Oral and Maxillofacial Surgery, General Hospital, Ningxia Medical University, Yinchuan, China
| | - Guangxun Zhu
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Mao
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Babak Baban
- Department of Oral Biology and Diagnostic Sciences, The Dental College of Georgia, Augusta University, Augusta, GA, USA
| | - Xu Qin
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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50
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Fraser D, Nguyen T, Benoit DSW. Matrix Control of Periodontal Ligament Cell Activity Via Synthetic Hydrogel Scaffolds. Tissue Eng Part A 2020; 27:733-747. [PMID: 33107404 DOI: 10.1089/ten.tea.2020.0278] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Rebuilding the tooth-supporting tissues (periodontium) destroyed by periodontitis remains a clinical challenge. Periodontal ligament cells (PDLCs), multipotent cells within the periodontal ligament (PDL), differentiate and form new PDL and mineralized tissues (cementum and bone) during native tissue repair in response to specific extracellular matrix (ECM) cues. Thus, harnessing ECM cues to control PDLC activity ex vivo, and ultimately, to design a PDLC delivery vehicle for tissue regeneration is an important goal. In this study, poly(ethylene glycol) hydrogels were used as a synthetic PDL ECM to interrogate the roles of cell-matrix interactions and cell-mediated matrix remodeling in controlling PDLC activity. Results showed that PDLCs within matrix metalloproteinase (MMP)-degradable hydrogels expressed key PDL matrix genes and showed a six to eightfold increase in alkaline phosphatase (ALP) activity compared with PDLCs in nondegradable hydrogel controls. The increase in ALP activity, commonly considered an early marker of cementogenic/osteogenic differentiation, occurred independent of the presentation of the cell-binding ligand RGD or soluble media cues and remained elevated when inhibiting PDLC-matrix binding and intracellular tension. ALP activity was further increased in softer hydrogels regardless of degradability and was accompanied by an increase in PDLC volume. However, scaffolds that fostered PDLC ALP activity did not necessarily promote hydrogel ECM mineralization. Rather, matrix mineralization was greatest in stiffer, MMP-degradable hydrogels and required the presence of soluble media cues. These divergent outcomes illustrate the complexity of the PDLC response to ECM cues and the limitations of current scaffold materials. Nevertheless, key biomaterial design principles for controlling PDLC activity were identified for incorporation into scaffolds for periodontal tissue regeneration. Impact statement Engineered scaffolds are an attractive approach for delivering periodontal ligament cells (PDLCs) to rebuild the tooth-supporting tissues. Replicating key extracellular matrix (ECM) cues within tissue engineered scaffolds may maximize PDLC potential. However, the identity of important ECM cues and how they can be harnessed to control PDLC activity is still unknown. In this study, matrix degradability, cell-matrix binding, and stiffness were varied using synthetic poly(ethylene glycol) hydrogels for three-dimensional PDLC culture. PDLCs exhibited dramatic and divergent responses to these cues, supporting further investigation of ECM-replicating scaffolds for control of PDLC behavior and periodontal tissue regeneration.
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Affiliation(s)
- David Fraser
- Translational Biomedical Science, University of Rochester, Rochester, New York, USA.,Eastman Institute for Oral Health, University of Rochester, Rochester, New York, USA
| | - Tram Nguyen
- Department of Biomedical Engineering, University of Rochester, Rochester, New York, USA
| | - Danielle S W Benoit
- Department of Biomedical Engineering, University of Rochester, Rochester, New York, USA.,Department of Chemical Engineering, University of Rochester, Rochester, New York, USA.,Materials Science Program, University of Rochester, Rochester, New York, USA.,Center for Oral Biology, University of Rochester, Rochester, New York, USA.,Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA
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