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Das P, Pal D, Roy S, Chaudhuri S, Kesh SS, Basak P, Nandi SK. Unveiling advanced strategies for therapeutic stem cell interventions in severe burn injuries: a comprehensive review. Int J Surg 2024; 110:6382-6401. [PMID: 38869979 PMCID: PMC11487052 DOI: 10.1097/js9.0000000000001812] [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: 02/03/2024] [Accepted: 05/29/2024] [Indexed: 06/15/2024]
Abstract
This comprehensive review explores the complex terrain of stem cell therapies as a potential therapeutic frontier in the healing of complicated burn wounds. Serious tissue damage, impaired healing processes, and possible long-term consequences make burn wounds a complex problem. An in-depth review is required since, despite medical progress, existing methods for treating severe burn wounds have significant limitations. Burn wounds are difficult to heal because they cause extensive tissue damage. The challenges of burn injury-induced tissue regeneration and functional recovery are also the subject of this review. Although there is a lot of promise in current stem cell treatments, there are also some limitations with scalability, finding the best way to transport the cells, and finding consistent results across different types of patients. To shed light on how to improve stem cell interventions to heal severe burn wounds, this review covers various stem cell applications in burn wounds and examines these obstacles. To overcome these obstacles, one solution is to enhance methods of stem cell distribution, modify therapies according to the severity of the burn, and conduct more studies on how stem cell therapy affects individual patients. Novel solutions may also be possible through the combination of cutting-edge technologies like nanotechnology and biotechnology. This review seeks to increase stem cell interventions by analyzing present challenges and suggesting strategic improvements. The goal is to provide a more effective and tailored way to repair serious burn wounds.
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Affiliation(s)
- Pratik Das
- Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences
- School of Bioscience and Engineering, Jadavpur University
| | - Debajyoti Pal
- Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences
| | - Sudipta Roy
- Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences
| | - Shubhamitra Chaudhuri
- Department of Veterinary Clinical Complex, West Bengal University of Animal and Fishery Sciences, Kolkata, India
| | - Shyam S. Kesh
- Department of Veterinary Clinical Complex, West Bengal University of Animal and Fishery Sciences, Kolkata, India
| | - Piyali Basak
- School of Bioscience and Engineering, Jadavpur University
| | - Samit K. Nandi
- Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences
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Yamada S, Yamada K, Sugawara-Narutaki A, Baba Y, Yukawa H. Near-infrared-II fluorescence/magnetic resonance double modal imaging of transplanted stem cells using lanthanide co-doped gadolinium oxide nanoparticles. ANAL SCI 2024; 40:1043-1050. [PMID: 38430367 DOI: 10.1007/s44211-024-00507-9] [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: 09/21/2023] [Accepted: 01/04/2024] [Indexed: 03/03/2024]
Abstract
To ensure maximum therapeutic safety and efficacy of stem cell transplantation, it is essential to observe the kinetics of behavior, accumulation, and engraftment of transplanted stem cells in vivo. However, it is difficult to detect transplanted stem cells with high sensitivity by conventional in vivo imaging technologies. To diagnose the kinetics of transplanted stem cells, we prepared multifunctional nanoparticles, Gd2O3 co-doped with Er3+ and Yb3+ (Gd2O3: Er, Yb-NPs), and developed an in vivo double modal imaging technique with near-infrared-II (NIR-II) fluorescence imaging and magnetic resonance imaging (MRI) of stem cells using Gd2O3: Er, Yb-NPs. Gd2O3: Er, Yb-NPs were transduced into adipose tissue-derived stem cells (ASCs) through a simple incubation process without cytotoxicity under certain concentrations of Gd2O3: Er, Yb-NPs and were found not to affect the morphology of ASCs. ASCs labeled with Gd2O3: Er, Yb-NPs were transplanted subcutaneously onto the backs of mice, and successfully imaged with good contrast using an in vivo NIR-II fluorescence imaging and MRI system. These data suggest that Gd2O3: Er, Yb-NPs may be useful for in vivo double modal imaging with NIR-II fluorescence imaging and MRI of transplanted stem cells.
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Affiliation(s)
- Shota Yamada
- Department of Energy Engineering, Graduate School of Engineering, Nagoya University, Furo-Cho, Chikusa-Ku, Nagoya, 464-8603, Japan.
| | - Kaori Yamada
- Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-Cho, Chikusa-Ku, Nagoya, 464-8603, Japan
| | - Ayae Sugawara-Narutaki
- Department of Energy Engineering, Graduate School of Engineering, Nagoya University, Furo-Cho, Chikusa-Ku, Nagoya, 464-8603, Japan
| | - Yoshinobu Baba
- Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-Cho, Chikusa-Ku, Nagoya, 464-8603, Japan
- Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-Cho, Chikusa-Ku, Nagoya, 464-8603, Japan
- Institute for Quantum Life Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Anagawa 4-9-1, Inage-Ku, Chiba, 263-8555, Japan
- Department of Medical-Engineering Collaboration Supported by SEI Group CSR Foundation, Nagoya University, Tsurumai 65, Showa-Ku, Nagoya, 466-8550, Japan
| | - Hiroshi Yukawa
- Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-Cho, Chikusa-Ku, Nagoya, 464-8603, Japan.
- Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-Cho, Chikusa-Ku, Nagoya, 464-8603, Japan.
- Institute for Quantum Life Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Anagawa 4-9-1, Inage-Ku, Chiba, 263-8555, Japan.
- Department of Medical-Engineering Collaboration Supported by SEI Group CSR Foundation, Nagoya University, Tsurumai 65, Showa-Ku, Nagoya, 466-8550, Japan.
- B-3Frontier, Advanced Analytical and Diagnostic Imaging Center (AADIC)/Medical Engineering Unit (MEU), Institute for Advanced Research, Nagoya University, Tsurumai 65, Showa-Ku, Nagoya, 466-8550, Japan.
- Department of Quantum Life Science, Graduate School of Science, Chiba University, Chiba, Japan.
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Strecanska M, Sekelova T, Csobonyeiova M, Danisovic L, Cehakova M. Therapeutic applications of mesenchymal/medicinal stem/signaling cells preconditioned with external factors: Are there more efficient approaches to utilize their regenerative potential? Life Sci 2024; 346:122647. [PMID: 38614298 DOI: 10.1016/j.lfs.2024.122647] [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: 02/21/2024] [Revised: 03/25/2024] [Accepted: 04/10/2024] [Indexed: 04/15/2024]
Abstract
Mesenchymal/medicinal stem/signaling cells (MSCs) have emerged as a promising treatment option for various disorders. However, the donor's age, advanced stage of disease, and prolonged in vitro expansion often diminish the innate regenerative potential of MSCs. Besides that, the absence of MSCs' comprehensive "pre-admission testing" can result in the injection of cells with reduced viability and function, which may negatively affect the overall outcome of MSC-based therapies. It is, therefore, essential to develop effective strategies to improve the impaired biological performance of MSCs. This review focuses on the comprehensive characterization of various methods of external MSCs stimulation (hypoxia, heat shock, caloric restriction, acidosis, 3D culture, and application of extracellular matrix) that augment their medicinal potential. To emphasize the significance of MSCs priming, we summarize the effects of individual and combined preconditioning approaches, highlighting their impact on MSCs' response to either physiological or pathological conditions. We further investigate the synergic action of exogenous factors to maximize MSCs' therapeutic potential. Not to omit the field of tissue engineering, the application of pretreated MSCs seeded on scaffolds is discussed as well.
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Affiliation(s)
- Magdalena Strecanska
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia; Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University Bratislava, Sasinkova 4, 811 08 Bratislava, Slovakia.
| | - Tatiana Sekelova
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia; Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University Bratislava, Sasinkova 4, 811 08 Bratislava, Slovakia.
| | - Maria Csobonyeiova
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University Bratislava, Sasinkova 4, 811 08 Bratislava, Slovakia.
| | - Lubos Danisovic
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia; Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University Bratislava, Sasinkova 4, 811 08 Bratislava, Slovakia.
| | - Michaela Cehakova
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University Bratislava, Sasinkova 4, 811 08 Bratislava, Slovakia.
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Mendoza AH, Balzarini D, Alves T, Rovai ES, Holzhausen M. Potential of Mesenchymal Stem Cell Sheets on Periodontal Regeneration: A Systematic Review of Pre-Clinical Studies. Curr Stem Cell Res Ther 2023; 18:958-978. [PMID: 35794765 DOI: 10.2174/1574888x17666220706092520] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 05/01/2022] [Accepted: 05/11/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Cell sheet technique using mesenchymal stem cells is a high-level strategy in periodontal regenerative medicine. Although recent studies have shown the role of MSCSs in increased dental supporting tissues and bone, there is no systematic review focused specifically on assessing periodontal regeneration in orthotopic animal models. OBJECTIVE To evaluate the potential of mesenchymal stem cell sheets (MSCSs) on periodontal regeneration, compared to control, in experimental animal models Methods: Pre-clinical studies in periodontal defects of animal models were considered eligible. The electronic search included the MEDLINE, Web of Science, EMBASE and LILACS databases. The review was conducted according to the Preferred Reporting Item for Systematic Reviews and Meta-Analyses statement guidelines. RESULTS A total of 17 of the 3989 studies obtained from the electronic database search were included. MSCSs included dental follicle (DF) MSCSs, periodontal ligament (PL) MSCSs, dental pulp (DP) MSCSs, bone marrow (BM) MSCSs, alveolar periosteal (AP) MSCSs and gingival (G) MSCSs. Regarding cell sheet inducing protocol, most of the studies used ascorbic acid (52.94%). Others used culture dishes grafted with a temperature-responsive polymer (47.06%). Adverse effects were not identified in the majority of studies. Meta-analysis was not considered because of methodological heterogeneities. PDL-MSCSs were superior for periodontal regeneration enhancement compared to the control, but in an induced inflammatory microenvironment, DF-MSCSs were better. Moreover, DF-MSCSs, DP-MSCSs, and BM-MSCSs showed improved results compared to the control. CONCLUSION MSCSs can improve periodontal regeneration in animal periodontal defect models.
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Affiliation(s)
- Aldrin Huamán Mendoza
- Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227, São Paulo, SP, Brazil
| | - Danilo Balzarini
- Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227, São Paulo, SP, Brazil
| | - Tomaz Alves
- Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227, São Paulo, SP, Brazil
| | - Emanuel S Rovai
- Division of Periodontology, Dental School, University of Taubaté, Rua dos Operários, 09, Centro, Taubaté, SP, Brazil
| | - Marinella Holzhausen
- Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227, São Paulo, SP, Brazil
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Wang L, Liu C, Song Y, Wu F. The effect of low-level laser irradiation on the proliferation, osteogenesis, inflammatory reaction, and oxidative stress of human periodontal ligament stem cells under inflammatory conditions. Lasers Med Sci 2022; 37:3591-3599. [PMID: 36104643 DOI: 10.1007/s10103-022-03638-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 08/22/2022] [Indexed: 10/14/2022]
Abstract
Periodontitis often causes damage to the periodontal tissue and affects the function of human periodontal ligament stem cells (hPDLSCs). Low-level laser therapy (LLLT) has been used for periodontal treatment and can upregulate the proliferation and osteogenesis of hPDLSCs. The purpose of this study was to investigate the effects of LLLT on the proliferation, osteogenic differentiation, inflammatory reaction, and oxidative stress of hPDLSCs in an inflammatory environment (pPDLSCs). We designed one control group and three testing groups (treated with Nd:YAG laser at 4, 8, and 16 J/cm2) of hPDLSCs from periodontitis patients who were diagnosed with stable phase periodontitis. Cell proliferation was measured by colony-forming unit fibroblast (CFU-F) assays and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The osteogenic capacity of the cells was determined by alkaline phosphatase (ALP) staining, ALP activity assays, Alizarin Red S staining and the mRNA transcript levels of runt-related transcription factor 2 (Runx2), ALP, and osteocalcin (OCN). The effects of LLLT on the secretion of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β by PDLSCs were measured by enzyme-linked immunosorbent assay (ELISA). We also evaluated the oxidative stress of hPDLSCs and pPDLSCs by measuring the reactive oxygen species (ROS) level, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity after treatment with LLLT at 4, 8, and 16 J/cm2. Our results demonstrated that LLLT could modulate the osteogenic potential of pPDLSCs at 8 J/cm2. Inflammatory stimuli induced excess ROS release, and LLLT at 4-8 J/cm2 promoted oxidative stress levels in hPDLSCs but decreased the expression of inflammatory cytokines and ROS levels in pPDLSCs. Moreover, LLLT at 16 J/cm2 could significantly suppress proliferation and osteogenic differentiation and promote inflammatory cytokines and ROS levels in pPDLSCs. In conclusion, LLLT could regulate proliferation, osteogenesis, inflammatory reaction, and oxidative stress of human periodontal ligament stem cells under inflammatory conditions.
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Affiliation(s)
- Liying Wang
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Chen Liu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of General Dentistry, Stomatological Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, China
| | - Yang Song
- Department of Stomatology, The Air Force 986 Hospital, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
| | - Fan Wu
- Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 145 West Changle Road, Xi'an, Shaanxi, 710032, People's Republic of China.
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Lin Y, Li Q, Wang L, Guo Q, Liu S, Zhu S, Sun Y, Fan Y, Sun Y, Li H, Tian X, Luo D, Shi S. Advances in regenerative medicine applications of tetrahedral framework nucleic acid-based nanomaterials: an expert consensus recommendation. Int J Oral Sci 2022; 14:51. [PMID: 36316311 PMCID: PMC9622686 DOI: 10.1038/s41368-022-00199-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 08/09/2022] [Accepted: 08/19/2022] [Indexed: 01/18/2023] Open
Abstract
With the emergence of DNA nanotechnology in the 1980s, self-assembled DNA nanostructures have attracted considerable attention worldwide due to their inherent biocompatibility, unsurpassed programmability, and versatile functions. Especially promising nanostructures are tetrahedral framework nucleic acids (tFNAs), first proposed by Turberfield with the use of a one-step annealing approach. Benefiting from their various merits, such as simple synthesis, high reproducibility, structural stability, cellular internalization, tissue permeability, and editable functionality, tFNAs have been widely applied in the biomedical field as three-dimensional DNA nanomaterials. Surprisingly, tFNAs exhibit positive effects on cellular biological behaviors and tissue regeneration, which may be used to treat inflammatory and degenerative diseases. According to their intended application and carrying capacity, tFNAs could carry functional nucleic acids or therapeutic molecules through extended sequences, sticky-end hybridization, intercalation, and encapsulation based on the Watson and Crick principle. Additionally, dynamic tFNAs also have potential applications in controlled and targeted therapies. This review summarized the latest progress in pure/modified/dynamic tFNAs and demonstrated their regenerative medicine applications. These applications include promoting the regeneration of the bone, cartilage, nerve, skin, vasculature, or muscle and treating diseases such as bone defects, neurological disorders, joint-related inflammatory diseases, periodontitis, and immune diseases.
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Affiliation(s)
- Yunfeng Lin
- grid.13291.380000 0001 0807 1581State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Qian Li
- grid.16821.3c0000 0004 0368 8293School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Lihua Wang
- grid.458506.a0000 0004 0497 0637The Interdisciplinary Research Center, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Zhangjiang Laboratory, Shanghai, China
| | - Quanyi Guo
- grid.488137.10000 0001 2267 2324Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, China
| | - Shuyun Liu
- grid.488137.10000 0001 2267 2324Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, China
| | - Shihui Zhu
- grid.73113.370000 0004 0369 1660Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Yu Sun
- grid.73113.370000 0004 0369 1660Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Yujiang Fan
- grid.13291.380000 0001 0807 1581National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China
| | - Yong Sun
- grid.13291.380000 0001 0807 1581College of Biomedical Engineering, Sichuan University, Chengdu, China
| | - Haihang Li
- Jiangsu Trautec Medical Technology Company Limited, Changzhou, China
| | - Xudong Tian
- Jiangsu Trautec Medical Technology Company Limited, Changzhou, China
| | - Delun Luo
- Chengdu Jingrunze Gene Technology Company Limited, Chengdu, China
| | - Sirong Shi
- grid.13291.380000 0001 0807 1581State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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Yamada S, Yukawa H, Yamada K, Murata Y, Jo JI, Yamamoto M, Sugawara-Narutaki A, Tabata Y, Baba Y. In Vivo Multimodal Imaging of Stem Cells Using Nanohybrid Particles Incorporating Quantum Dots and Magnetic Nanoparticles. SENSORS (BASEL, SWITZERLAND) 2022; 22:5705. [PMID: 35957262 PMCID: PMC9371134 DOI: 10.3390/s22155705] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 07/25/2022] [Accepted: 07/28/2022] [Indexed: 06/15/2023]
Abstract
The diagnosis of the dynamics, accumulation, and engraftment of transplanted stem cells in vivo is essential for ensuring the safety and the maximum therapeutic effect of regenerative medicine. However, in vivo imaging technologies for detecting transplanted stem cells are not sufficient at present. We developed nanohybrid particles composed of dendron-baring lipids having two unsaturated bonds (DLU2) molecules, quantum dots (QDs), and magnetic nanoparticles in order to diagnose the dynamics, accumulation, and engraftment of transplanted stem cells, and then addressed the labeling and in vivo fluorescence and magnetic resonance (MR) imaging of stem cells using the nanohybrid particles (DLU2-NPs). Five kinds of DLU2-NPs (DLU2-NPs-1-5) composed of different concentrations of DLU2 molecules, QDs525, QDs605, QDs705, and ATDM were prepared. Adipose tissue-derived stem cells (ASCs) were labeled with DLU2-NPs for 4 h incubation, no cytotoxicity or marked effect on the proliferation ability was observed in ASCs labeled with DLU2-NPs (640- or 320-fold diluted). ASCs labeled with DLU2-NPs (640-fold diluted) were transplanted subcutaneously onto the backs of mice, and the labeled ASCs could be imaged with good contrast using in vivo fluorescence and an MR imaging system. DLU2-NPs may be useful for in vivo multimodal imaging of transplanted stem cells.
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Affiliation(s)
- Shota Yamada
- Department of Energy Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan; (S.Y.); (A.S.-N.)
| | - Hiroshi Yukawa
- Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan; (K.Y.); (Y.B.)
- Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan
- Institute for Quantum Life Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Anagawa 4-9-1, Inage-ku, Chiba 263-8555, Japan
- B-3Frontier, Advanced Analytical and Diagnostic Imaging Center (AADIC)/Medical Engineering Unit (MEU), Institute for Advanced Research, Nagoya University, Tsurumai 65, Showa-ku, Nagoya 466-8550, Japan
- Department of Medical-Engineering Collaboration Supported by SEI Group CSR Foundation, Nagoya University, Tsurumai 65, Showa-ku, Nagoya 466-8550, Japan
| | - Kaori Yamada
- Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan; (K.Y.); (Y.B.)
| | - Yuki Murata
- Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; (Y.M.); (J.-i.J.); (Y.T.)
| | - Jun-ichiro Jo
- Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; (Y.M.); (J.-i.J.); (Y.T.)
| | - Masaya Yamamoto
- Department of Metallurgy, Materials Science and Materials Processing, Graduate School of Engineering, Tohoku University, Aoba-yama 02, Aoba-ku, Sendai 980-8579, Japan;
| | - Ayae Sugawara-Narutaki
- Department of Energy Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan; (S.Y.); (A.S.-N.)
| | - Yasuhiko Tabata
- Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; (Y.M.); (J.-i.J.); (Y.T.)
| | - Yoshinobu Baba
- Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan; (K.Y.); (Y.B.)
- Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan
- Institute for Quantum Life Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Anagawa 4-9-1, Inage-ku, Chiba 263-8555, Japan
- Department of Medical-Engineering Collaboration Supported by SEI Group CSR Foundation, Nagoya University, Tsurumai 65, Showa-ku, Nagoya 466-8550, Japan
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Bousnaki M, Beketova A, Kontonasaki E. A Review of In Vivo and Clinical Studies Applying Scaffolds and Cell Sheet Technology for Periodontal Ligament Regeneration. Biomolecules 2022; 12:435. [PMID: 35327627 PMCID: PMC8945901 DOI: 10.3390/biom12030435] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 03/06/2022] [Accepted: 03/08/2022] [Indexed: 12/14/2022] Open
Abstract
Different approaches to develop engineered scaffolds for periodontal tissues regeneration have been proposed. In this review, innovations in stem cell technology and scaffolds engineering focused primarily on Periodontal Ligament (PDL) regeneration are discussed and analyzed based on results from pre-clinical in vivo studies and clinical trials. Most of those developments include the use of polymeric materials with different patterning and surface nanotopography and printing of complex and sophisticated multiphasic composite scaffolds with different compartments to accomodate for the different periodontal tissues' architecture. Despite the increased effort in producing these scaffolds and their undoubtable efficiency to guide and support tissue regeneration, appropriate source of cells is also needed to provide new tissue formation and various biological and mechanochemical cues from the Extraccellular Matrix (ECM) to provide biophysical stimuli for cell growth and differentiation. Cell sheet engineering is a novel promising technique that allows obtaining cells in a sheet format while preserving ECM components. The right combination of those factors has not been discovered yet and efforts are still needed to ameliorate regenerative outcomes towards the functional organisation of the developed tissues.
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Affiliation(s)
| | | | - Eleana Kontonasaki
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (M.B.); (A.B.)
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9
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Li ZB, Yang HQ, Li K, Yin Y, Feng SS, Ge SH, Yu Y. Comprehensive Transcriptome Analysis of mRNA Expression Patterns Associated With Enhanced Biological Functions in Periodontal Ligament Stem Cells Subjected to Short-Term Hypoxia Pretreatment. Front Genet 2022; 13:797055. [PMID: 35211157 PMCID: PMC8861432 DOI: 10.3389/fgene.2022.797055] [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: 10/18/2021] [Accepted: 01/13/2022] [Indexed: 11/20/2022] Open
Abstract
Short-term hypoxia pretreatment significantly enhances periodontal ligament stem cell (PDLSC)-based periodontal tissue regeneration by improving various cellular biological functions, but the underlying mechanisms remain unclear. In this study, based on RNA sequencing (RNA-seq), we comprehensively analyzed the possible regulatory mechanisms of the short-term hypoxic effects on the biological functions of healthy and inflammatory PDLSCs. A total of 134 and 164 differentially expressed genes (DEGs) were identified under healthy and inflammatory conditions, respectively. Functional enrichment analyses indicated that DEGs under both conditions share certain biological processes and pathways, including metabolic processes, developmental processes, reproductive processes, localization, immune system processes and the HIF-1 signaling pathway. The DEGs identified under inflammatory conditions were more significantly enriched in cell cycle-related processes and immune-related pathways, while DEGs identified under healthy condition were more significantly enriched in the TGF-β signaling pathway. A protein-protein interaction network analysis of the 59 DEGs in both conditions was performed, and 15 hub genes were identified. These hub genes were mainly involved in glycolysis, the cellular response to hypoxia, cell differentiation, and immune system processes. In addition, we found that hypoxia induced significant differential expression of genes associated with proliferation, differentiation, migration, apoptosis and immunoregulation under both healthy and inflammatory conditions. This study provides comprehensive insights into the effects of short-term hypoxia on the biological functions of PDLSCs and suggests a potentially feasible strategy for improving the clinical effectiveness of cell-based periodontal tissue engineering.
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Affiliation(s)
- Zhi-Bang Li
- Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China.,State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Hui-Qi Yang
- Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Kun Li
- Department of Periodontology, Jinan Stomatological Hospital, Jinan, China
| | - Yuan Yin
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Su-Su Feng
- Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Shao-Hua Ge
- Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yang Yu
- Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China
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10
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Guan X, He Y, Li Y, Shi C, Wei Z, Zhao R, Han Y, Pan L, Yang J, Hou TZ. Gremlin aggravates periodontitis via activating the NF-κB signaling pathway. J Periodontol 2022; 93:1589-1602. [PMID: 34993960 DOI: 10.1002/jper.21-0474] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/27/2021] [Accepted: 11/20/2021] [Indexed: 11/06/2022]
Abstract
BACKGROUND Gremlin has been reported to regulate inflammation and osteogenesis. Periodontitis is a destructive disease degenerating periodontal tissues, therefore leads to alveolar bone resorption and tooth loss. Based on the importance of Gremlin's bio-activity, the aim of this study is to, in vivo and in vitro, unveil the function of Gremlin in regulating the development of periodontitis and its consequent effects on alveolar bone loss. METHODS Clinical specimens were used to determine the expression of Gremlin in periodontal tissues by immunohistochemical staining and western blot. Then utilizing the rat periodontitis model to investigate the function of gremlin-regulated nuclear factor-kappa B (NF-κB) pathway during the development of periodontal inflammation and the alveolar bone loss. Lastly, the regulation of the osteogenesis of human periodontal ligament stem cells (hPDLSCs) by Gremlin under inflamed condition was analyzed by alkaline phosphatase (ALP) and alizarin red staining (ARS). RESULTS We found clinically and experimentally that the expression of Gremlin is markedly increased in periodontitis tissues. Interestingly, we revealed that Gremlin regulated the progress of periodontitis via regulating the activities of NF-κB pathway and interleukin-1β (IL-1β). Notably, we observed that Gremlin influenced the osteogenesis of hPDLSCs. Thus, our present study identified Gremlin as a new key regulator for development of periodontitis. CONCLUSIONS Our current study illustrated that Gremlin acts as a crucial mediator and possibly serves as a potential diagnostic marker for periodontitis. Discovery of new factors involved in the pathophysiology of periodontitis could contribute to the development of novel therapeutic treatment for the disease. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Xiaoyue Guan
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China
| | - Yani He
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China
| | - Yingxue Li
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China
| | - Chen Shi
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China
| | - Zhichen Wei
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China
| | - Rui Zhao
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China
| | - Yue Han
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China
| | - Lifei Pan
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China
| | - Jianmin Yang
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Tie Zhou Hou
- The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Department of Endodontics, Stomatological Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China
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11
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Okić-Đorđević I, Obradović H, Kukolj T, Petrović A, Mojsilović S, Bugarski D, Jauković A. Dental mesenchymal stromal/stem cells in different microenvironments— implications in regenerative therapy. World J Stem Cells 2021; 13:1863-1880. [PMID: 35069987 PMCID: PMC8727232 DOI: 10.4252/wjsc.v13.i12.1863] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/15/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Current research data reveal microenvironment as a significant modifier of physical functions, pathologic changes, as well as the therapeutic effects of stem cells. When comparing regeneration potential of various stem cell types used for cytotherapy and tissue engineering, mesenchymal stem cells (MSCs) are currently the most attractive cell source for bone and tooth regeneration due to their differentiation and immunomodulatory potential and lack of ethical issues associated with their use. The microenvironment of donors and recipients selected in cytotherapy plays a crucial role in regenerative potential of transplanted MSCs, indicating interactions of cells with their microenvironment indispensable in MSC-mediated bone and dental regeneration. Since a variety of MSC populations have been procured from different parts of the tooth and tooth-supporting tissues, MSCs of dental origin and their achievements in capacity to reconstitute various dental tissues have gained attention of many research groups over the years. This review discusses recent advances in comparative analyses of dental MSC regeneration potential with regards to their tissue origin and specific microenvironmental conditions, giving additional insight into the current clinical application of these cells.
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Affiliation(s)
- Ivana Okić-Đorđević
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Hristina Obradović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Tamara Kukolj
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Anđelija Petrović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Slavko Mojsilović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Diana Bugarski
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Aleksandra Jauković
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
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12
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Zhang SY, Ren JY, Yang B. Priming strategies for controlling stem cell fate: Applications and challenges in dental tissue regeneration. World J Stem Cells 2021; 13:1625-1646. [PMID: 34909115 PMCID: PMC8641023 DOI: 10.4252/wjsc.v13.i11.1625] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 05/14/2021] [Accepted: 08/27/2021] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stromal cells (MSCs) have attracted intense interest in the field of dental tissue regeneration. Dental tissue is a popular source of MSCs because MSCs can be obtained with minimally invasive procedures. MSCs possess distinct inherent properties of self-renewal, immunomodulation, proangiogenic potential, and multilineage potency, as well as being readily available and easy to culture. However, major issues, including poor engraftment and low survival rates in vivo, remain to be resolved before large-scale application is feasible in clinical treatments. Thus, some recent investigations have sought ways to optimize MSC functions in vitro and in vivo. Currently, priming culture conditions, pretreatment with mechanical and physical stimuli, preconditioning with cytokines and growth factors, and genetic modification of MSCs are considered to be the main strategies; all of which could contribute to improving MSC efficacy in dental regenerative medicine. Research in this field has made tremendous progress and continues to gather interest and stimulate innovation. In this review, we summarize the priming approaches for enhancing the intrinsic biological properties of MSCs such as migration, antiapoptotic effect, proangiogenic potential, and regenerative properties. Challenges in current approaches associated with MSC modification and possible future solutions are also indicated. We aim to outline the present understanding of priming approaches to improve the therapeutic effects of MSCs on dental tissue regeneration.
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Affiliation(s)
- Si-Yuan Zhang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia-Yin Ren
- Department of Oral Radiology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Bo Yang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
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13
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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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14
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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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15
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Gholami L, Hendi SS, Saidijam M, Mahmoudi R, Tarzemany R, Arkian A, Afshar S, Fekrazad R. Near-infrared 940-nm diode laser photobiomodulation of inflamed periodontal ligament stem cells. Lasers Med Sci 2021; 37:449-459. [PMID: 33740139 DOI: 10.1007/s10103-021-03282-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 03/01/2021] [Indexed: 10/21/2022]
Abstract
Photobiomodulation (PBM) is an acceptable method of stimulating stem cells through its non-invasive absorption by the cell photoreceptors and the induction of cellular response. The current research was aimed at evaluating the effect of near-infrared PBM on proliferation and osteogenic differentiation in inflamed periodontal ligament stem cells (I-PDLSCs). I-PDLSCs were isolated and characterized. Third passage cells were irradiated with 940-nm laser at an output power of 100 mW in a continuous wave. A fluence of 4 J/cm2 in three sessions at 48-h intervals was applied and compared with non-irradiated controls. Cell viability and proliferation were evaluated by MTT assay. Alkaline phosphatase activity, quantitative Alizarin red staining test, and q-RT-PCR were used to evaluate the osteogenic properties of the I-PDLSCs in four groups of (a) osteogenic differentiation medium + laser (ODM + L), (b) osteogenic differentiation medium without laser (ODM), (c) non-osteogenic differentiation medium + laser (L), and (d) non-osteogenic differentiation medium (control). There was a non-significant increase in the viability of cells at 48- and 72-h post last laser irradiation. Alizarin red staining revealed no significant stimulatory effect of PBM at 14 and 21 days. However, alkaline phosphatase activity was significantly higher in the L + ODM group. Expression of osteogenic-related genes had a statistically significant increase at 21-day post irradiation. The irradiation used in the present study showed no significant increase in the proliferation of I-PDLSCs by PBM. However, expression levels of osteogenic-related genes and alkaline phosphatase activity were significantly increased in irradiated groups.
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Affiliation(s)
- Leila Gholami
- Department of Periodontics, Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Seyedeh Sareh Hendi
- Department of Endodontics, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Massoud Saidijam
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Roghayeh Mahmoudi
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Rana Tarzemany
- Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, Canada
| | - Aliasghar Arkian
- Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Saeid Afshar
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Reza Fekrazad
- Radiation Sciences Research Center, Laser Research Center in Medical Sciences, AJA University of Medical Sciences, Tehran, Iran.,International Network for Photomedicine and Photo Dynamic Therapy (INPMPDT), Universal Scientific Education and Research Network (USERN), Tehran, Iran
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16
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Li Z, Pan W, Shi E, Bai L, Liu H, Li C, Wang Y, Deng J, Wang Y. A Multifunctional Nanosystem Based on Bacterial Cell-Penetrating Photosensitizer for Fighting Periodontitis Via Combining Photodynamic and Antibiotic Therapies. ACS Biomater Sci Eng 2021; 7:772-786. [PMID: 33411504 DOI: 10.1021/acsbiomaterials.0c01638] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Photodynamic therapy (PDT), an emerging approach that involves photosensitizers, light, and molecular oxygen, has shown promise for fighting periodontitis. However, PDT does not always acquire the desired therapeutic outcomes since some photosensitizers have strong hydrophobic properties and are difficult to absorb efficiently by periodontal pathogenic bacteria. Here, a hydrophobic photosensitizer chlorin e6 (Ce6) was hydrophilically modified via conjugation with TAT peptide, a cationic cell-penetrating peptide, to improve its solubility and enhance its bacterial adsorption by promoting its interaction with the negatively charged cell walls and penetration through the cell membranes. The obtained TAT-Ce6 conjugate (TAT-Ce6) was used to prepare self-assembled nanoparticles (NPs) for loading tinidazole (TDZ), a clinically used antibiotic agent, thus hoping to achieve synergistic antiperiodontitis effects through combining PDT and antibiotic therapy. Compared to free Ce6, TAT-Ce6 nanoparticles (TAT-Ce6 NPs) had greatly enhanced adsorption and penetration abilities for periodontal pathogen bacteria and also exhibited significantly increased PDT efficiencies in both periodontal pathogen bacteria and monocyte macrophages. Upon 635 nm laser irradiation, TDZ-loaded TAT-Ce6 (TAT-Ce6/TDZ) NPs exerted remarkable synergistic antiperiodontitis effects of PDT and antibiotic therapy, reflecting in the effective killing of periodontal pathogenic bacteria in vitro and the reduced adsorption of alveolar bone in the Sprague-Dawley rat model of periodontitis. Altogether, this study develops a novel photosensitizer that can be efficiently absorbed by the periodontal pathogenic bacteria and also provides a potent combination strategy of PDT with antibiotic therapy for clinical periodontitis treatment.
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Affiliation(s)
- Zhiyuan Li
- School of Dentistry & Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, P. R. China
| | - Wei Pan
- School of Dentistry & Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, P. R. China
| | - Enyu Shi
- School of Dentistry & Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, P. R. China
| | - Liya Bai
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China
| | - Hui Liu
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China
| | - Changyi Li
- School of Dentistry & Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, P. R. China
| | - Yinsong Wang
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China
| | - Jiayin Deng
- School of Dentistry & Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, P. R. China
| | - Yue Wang
- School of Dentistry & Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, P. R. China
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17
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Li Q, Yang G, Li J, Ding M, Zhou N, Dong H, Mou Y. Stem cell therapies for periodontal tissue regeneration: a network meta-analysis of preclinical studies. Stem Cell Res Ther 2020; 11:427. [PMID: 33008471 PMCID: PMC7531120 DOI: 10.1186/s13287-020-01938-7] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 09/16/2020] [Indexed: 12/18/2022] Open
Abstract
Background Periodontal tissue regeneration (PTR) is the ultimate goal of periodontal therapy. Currently, stem cell therapy is considered a promising strategy for achieving PTR. However, there is still no conclusive comparison that distinguishes clear hierarchies among different kinds of stem cells. Methods A systematic review and network meta-analysis (NMA) was performed using MEDLINE (via PubMed), EMBASE, and Web of Science up to February 2020. Preclinical studies assessing five types of stem cells for PTR were included; the five types of stem cells included periodontal ligament-derived stem cells (PDLSCs), bone marrow-derived stem cells (BMSCs), adipose tissue-derived stem cells (ADSCs), dental pulp-derived stem cells (DPSCs), and gingival-derived stem cells (GMSCs). The primary outcomes were three histological indicators with continuous variables: newly formed alveolar bone (NB), newly formed cementum (NC), and newly formed periodontal ligament (NPDL). We performed pairwise meta-analyses using a random-effects model and then performed a random-effects NMA using a multivariate meta-analysis model. Results Sixty preclinical studies assessing five different stem cell-based therapies were identified. The NMA showed that in terms of NB, PDLSCs (standardized mean difference 1.87, 95% credible interval 1.24 to 2.51), BMSCs (1.88, 1.17 to 2.59), and DPSCs (1.69, 0.64 to 2.75) were statistically more efficacious than cell carriers (CCs). In addition, PDLSCs were superior to GMSCs (1.49, 0.04 to 2.94). For NC, PDLSCs (2.18, 1.48 to 2.87), BMSCs (2.11, 1.28 to 2.94), and ADSCs (1.55, 0.18 to 2.91) were superior to CCs. For NPDL, PDLSCs (1.69, 0.92 to 2.47) and BMSCs (1.41, 0.56 to 2.26) were more efficacious than CCs, and PDLSCs (1.26, 0.11 to 2.42) were superior to GMSCs. The results of treatment hierarchies also demonstrated that the two highest-ranked interventions were PDLSCs and BMSCs. Conclusion PDLSCs and BMSCs were the most effective and well-documented stem cells for PTR among the five kinds of stem cells evaluated in this study, and there was no statistical significance between them. To translate the stem cell therapies for PTR successfully in the clinic, future studies should utilize robust experimental designs and reports.
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Affiliation(s)
- Qiang Li
- Department of Oral Implantology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.,Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Guangwen Yang
- Department of Oral Implantology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.,Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jialing Li
- Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.,Department of Orthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Meng Ding
- Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Na Zhou
- Department of Oral Implantology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Heng Dong
- Department of Oral Implantology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China. .,Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
| | - Yongbin Mou
- Department of Oral Implantology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
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18
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Yao C, Zhang Q, Li J, She P, Kong F, Du Y, Zhang F. Implantable zoledronate-PLGA microcapsules ameliorate alveolar bone loss, gingival inflammation and oxidative stress in an experimental periodontitis rat model. J Biomater Appl 2020; 35:569-578. [PMID: 32772779 DOI: 10.1177/0885328220944683] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
The effect of implantable Zoledronate-PLGA microcapsules (PLGA-ZOL) in periodontitis remains unclear. In this study, we aimed to explore the potential role of PLGA-ZOL in protecting periodontitis and elucidate the underlying mechanism. A rat model of periodontitis was established by ligation the mandibular first molars, then PLGA-ZOL was implanted. The healing volume was scanned by cone-beam computed tomography. Cytokine levels in the gingival tissues were determined by ELISA and RT-PCR. Oxidative stress was indicated by detecting superoxide dismutase concentration and catalase activity. After periodontitis model was successfully established in rats, PLGA-ZOL treatment significantly attenuated alveolar bone loss, as indicated by the increased total healing volume, bone volume/tissue volume and osteoprotegerin level, as well as decreased sRANKL level. PLGA-ZOL treatment also suppressed the inflammatory activities by inhibiting pro-inflammatory cytokine production (TNF-α, IL-1β) but increasing anti-inflammatory cytokine secretion (IL-10). Furthermore, PLGA-ZOL was found to ameliorate oxidative stress in gingival tissues. In conclusion, PLGA-ZOL microcapsules ameliorate alveolar bone loss, gingival inflammation and oxidative stress in an experimental rat model of periodontitis.
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Affiliation(s)
- Chun Yao
- The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Stomatology, Zhenjiang First People's Hospital, Department of Stomatology, People's Hospital Affiliated to Jiangsu University, Dianli Road, Zhenjiang, China
| | - Qingqing Zhang
- The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Stomatology, Jiangning Hospital Affiliated to Nanjing Medicine University, Nanjing, China
| | - Jun Li
- The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Stomatology, Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Peng She
- Department of Stomatology, Zhenjiang First People's Hospital, Department of Stomatology, People's Hospital Affiliated to Jiangsu University, Dianli Road, Zhenjiang, China
| | - Fanzhi Kong
- Department of Stomatology, Zhenjiang First People's Hospital, Department of Stomatology, People's Hospital Affiliated to Jiangsu University, Dianli Road, Zhenjiang, China
| | - Yanxiao Du
- The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Stomatology, Qingdao Central Hospital, Qingdao, China
| | - Feimin Zhang
- The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
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19
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Duan Y, An W, Wu Y, Wang J. Tetramethylpyrazine reduces inflammation levels and the apoptosis of LPS‑stimulated human periodontal ligament cells via the downregulation of miR‑302b. Int J Mol Med 2020; 45:1918-1926. [PMID: 32236610 PMCID: PMC7169953 DOI: 10.3892/ijmm.2020.4554] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Accepted: 03/12/2020] [Indexed: 12/22/2022] Open
Abstract
Periodontitis is the main cause of tooth or tissue loss. Human periodontal ligament stem cells (hPDLSCs), which have high proliferative, self-renewal and multi-differentiation abilities, are vital for the restoration of periodontitis-induced injuries. The anti-inflammatory and anti-apoptotic agent, tetramethylpyrazine (TMP), is a promising agent used for the protection of PDLSCs from apoptosis and inflammation induced by periodontitis. The aim of the present study was to investigate the effects of TMP on lipopolysaccharide (LPS)-stimulated hPDLSCs. LPS-stimulated hPDLSCs were established as the cell model. CCK-8 assay was performed to evaluate cell viability, western blot analysis was performed to measure protein expression and flow cytometry was performed to detect cell apoptosis levels. Detection kits were used to evaluate the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. Reverse transcription-quantitative PCR analysis was performed to detect gene expression. TMP alleviated the effects of LPS on cell viability, inflammation levels and cell apoptosis. TMP downregulated microRNA (miR)-302b levels in LPS-stimulated cells. Transfection with miR-302b mimic reversed the anti-inflammatory and anti-apoptotic effects of TMP on LPS-stimulated cells. TMP reduced inflammation and the apoptosis of LPS-stimulated human periodontal ligament cells via the downregulation of miR-302b. The anti-inflammatory and anti-apoptotic effects exerted by TMP render it a promising agent for the protection of PDLSCs from injuries induced by periodontitis. The findings of the present study may aid in the development of a novel strategy for the treatment of periodontitis and may pave the way for further research.
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Affiliation(s)
- Yan Duan
- Department of Oral Medicine, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030000, P.R. China
| | - Wei An
- Department of Oral Surgery, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030000, P.R. China
| | - Yunxia Wu
- Department of Oral Medicine, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
| | - Jin Wang
- Department of Oral and Maxillofacial Surgery, Jinan Stomatological Hospital, Jinan, Shandong 250000, P.R. China
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20
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Ni C, Zhou J, Kong N, Bian T, Zhang Y, Huang X, Xiao Y, Yang W, Yan F. Gold nanoparticles modulate the crosstalk between macrophages and periodontal ligament cells for periodontitis treatment. Biomaterials 2019; 206:115-132. [DOI: 10.1016/j.biomaterials.2019.03.039] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Accepted: 03/23/2019] [Indexed: 12/12/2022]
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21
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Chen Y, Zhao Q, Yang X, Yu X, Yu D, Zhao W. Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth. Cell Stress Chaperones 2019; 24:527-538. [PMID: 30806897 PMCID: PMC6527733 DOI: 10.1007/s12192-019-00981-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 01/23/2019] [Accepted: 02/07/2019] [Indexed: 12/19/2022] Open
Abstract
Stem cells from human exfoliated deciduous teeth (SHEDs) are a promising source for tissue engineering and stem cell transplantation. However, long-term in vitro culture and expansion lead to the loss of stemness of SHEDs, compromising their therapeutic benefits. Hypoxia plays an essential role in controlling the stem cell behavior of mesenchymal stem cells (MSCs). Thus, this study aimed to investigate the effects of cobalt chloride (CoCl2), a hypoxia-mimetic agent, on the stem cell marker expression and osteogenic differentiation of SHEDs. SHEDs were cultured with or without 50 or 100 μM CoCl2. Their proliferation, apoptosis, stem cell marker expression, migration ability, and osteogenic differentiation were examined. Culture with 50 and 100 μM CoCl2 increased the hypoxia-inducible factor-1 alpha (HIF-1α) protein levels in a dose-dependent manner in SHEDs without inducing significant cytotoxicity. This effect was accompanied by an increase in the proportion of STRO-1+ cells. CoCl2 significantly increased the expression of stem cell markers (OCT4, NANOG, SOX2, and c-Myc) in a dose-dependent manner. The migration ability was also promoted by CoCl2 treatment. Furthermore, SHEDs cultured in osteogenic medium with CoCl2 showed a dose-dependent reduction in alkaline phosphatase (ALP) activity and calcium deposition. The expression of osteogenic-related genes was also suppressed by CoCl2, especially in the 100-μM CoCl2 group. In conclusion, CoCl2 increased the expression of stem cell markers and inhibited the osteogenic differentiation of SHEDs. These findings may provide evidence supporting the use of in vitro hypoxic environments mimicked by CoCl2 in assisting the clinical application of SHEDs.
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Affiliation(s)
- Yijing Chen
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, No. 56 Lingyuan West Road, Guangzhou, 510055, China
| | - Qi Zhao
- Xianning Central Hospital, The First Affiliated Hospital Of Hubei University of Science and Technology, Xianning, 437000, China
| | - Xin Yang
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, No. 56 Lingyuan West Road, Guangzhou, 510055, China
| | - Xinlin Yu
- International Department, The Affiliated High School of SCNU, Guangzhou, 510630, China
| | - Dongsheng Yu
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, No. 56 Lingyuan West Road, Guangzhou, 510055, China.
| | - Wei Zhao
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, No. 56 Lingyuan West Road, Guangzhou, 510055, China.
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22
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Fawzy El-Sayed KM, Elahmady M, Adawi Z, Aboushadi N, Elnaggar A, Eid M, Hamdy N, Sanaa D, Dörfer CE. The periodontal stem/progenitor cell inflammatory-regenerative cross talk: A new perspective. J Periodontal Res 2019; 54:81-94. [PMID: 30295324 DOI: 10.1111/jre.12616] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Revised: 07/24/2018] [Accepted: 08/31/2018] [Indexed: 12/13/2022]
Abstract
Adult multipotent stem/progenitor cells, with remarkable regenerative potential, have been isolated from various components of the human periodontium. These multipotent stem/progenitor cells include the periodontal ligament stem/progenitor cells (PDLSCs), stem cells from the apical papilla (SCAP), the gingival mesenchymal stem/progenitor cells (G-MSCs), and the alveolar bone proper stem/progenitor cells (AB-MSCs). Whereas inflammation is regarded as the reason for tissue damage, it also remains a fundamental step of any early healing process. In performing their periodontal tissue regenerative/reparative activity, periodontal stem/progenitor cells interact with their surrounding inflammatory micro-environmental, through their expressed receptors, which could influence their fate and the outcome of any periodontal stem/progenitor cell-mediated reparative/regenerative activity. The present review discusses the current understanding about the interaction of periodontal stem/progenitor cells with their surrounding inflammatory micro-environment, elaborates on the inflammatory factors influencing their stemness, proliferation, migration/homing, differentiation, and immunomodulatory attributes, the possible underlying intracellular mechanisms, as well as their proposed relationship to the canonical and noncanonical Wnt pathways.
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Affiliation(s)
- Karim M Fawzy El-Sayed
- Oral Medicine and Periodontology Department, Faculty of Oral and Dental Medicine, Cairo University, Cairo, Egypt
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
| | | | - Zeina Adawi
- Faculty of Dentistry, New Giza University, Giza, Egypt
| | | | - Ali Elnaggar
- Faculty of Dentistry, New Giza University, Giza, Egypt
| | - Maryam Eid
- Faculty of Dentistry, New Giza University, Giza, Egypt
| | - Nayera Hamdy
- Faculty of Dentistry, New Giza University, Giza, Egypt
| | - Dalia Sanaa
- Faculty of Dentistry, New Giza University, Giza, Egypt
| | - Christof E Dörfer
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
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23
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Xu XY, He XT, Wang J, Li X, Xia Y, Tan YZ, Chen FM. Role of the P2X7 receptor in inflammation-mediated changes in the osteogenesis of periodontal ligament stem cells. Cell Death Dis 2019; 10:20. [PMID: 30622236 PMCID: PMC6325129 DOI: 10.1038/s41419-018-1253-y] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Revised: 11/06/2018] [Accepted: 12/03/2018] [Indexed: 02/06/2023]
Abstract
Accumulating evidence indicates that the pluripotency of periodontal ligament stem cells (PDLSCs) is compromised under inflammatory conditions; however, the underlying mechanisms remain largely unexplored. In this study, we hypothesize that the P2X7 receptor (P2X7R) is a key molecule linked to inflammation-associated impairment of PDLSCs. We first investigated P2X7R expression in PDLSCs under normal and inflammatory conditions and then determined the effect of a P2X7R agonist (BzATP) or antagonist (BBG) on PDLSC osteogenesis under various conditions. Gene-modified PDLSCs were used to further examine the role of P2X7R and the signaling pathway underlying P2X7R-enhanced osteogenesis. We found that inflammatory conditions decreased P2X7R expression in PDLSCs and reduced osteogenesis in these cells. In addition, activation of P2X7R by BzATP or overexpression of P2X7R via gene transduction reversed the inflammation-mediated decrease in PDLSC osteogenic differentiation. When selected osteogenesis-related signaling molecules were screened, the PI3K-AKT-mTOR pathway was identified as potentially involved in P2X7R-enhanced PDLSC osteogenesis. Our data reveal a crucial role for P2X7R in PDLSC osteogenesis under inflammatory conditions, suggesting a new therapeutic target to reverse or rescue inflammation-mediated changes in PDLSCs for future mainstream therapeutic uses.
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Affiliation(s)
- Xin-Yue Xu
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Xiao-Tao He
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Jia Wang
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Xuan Li
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Yu Xia
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Yi-Zhou Tan
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Fa-Ming Chen
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
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24
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Liu X, Sun H, Yu M, Liu J, Yang B, Wu Y, Wang J. DDIT3 regulates cementoblast mineralization by isocitrate dehydrogenase 1 through nuclear factor-κB pathway. J Cell Physiol 2018; 234:11602-11609. [PMID: 30488444 DOI: 10.1002/jcp.27811] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Accepted: 11/06/2018] [Indexed: 02/06/2023]
Abstract
DDIT3 is of great importance in endoplasmic reticulum stress and is involved in many inflammatory diseases and mineralization processes. The cementum protects teeth from periodontitis and provides attachment for Sharpey's fibers of the periodontal ligament. However, the effect of DDIT3 on cementoblast differentiation remains largely unknown. In this study, we found that DDIT3 was suppressed during cementoblast differentiation. Knockdown of DDIT3 increased the messenger RNA (mRNA) and protein levels of several key osteogenic markers in vitro, including alkaline phosphatase, runt-related transcription factor 2, and osteocalcin (OCN). In addition, isocitrate dehydrogenase 1 (IDH1) was increased during cementoblast differentiation, and knockdown of DDIT3 increased the protein and mRNA levels of IDH1. Furthermore, inhibition of IDH1 could partially reduce the effect of DDIT3 on cementoblast differentiation. The DDIT3 knockdown activated nuclear factor-κB (NF-κB) transcriptional activity and upregulated the expression of p-p65 and p-IκBα. The increased osteogenic differentiation ability and IDH1 expression, as induced by the DDIT3 knockdown, could be partially turned over by the addition of NF-κB inhibitor BAY 11-7082. Overall, our data clarified that DDIT3 suppresses cementoblast differentiation through IDH1, via the NF-κB pathway.
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Affiliation(s)
- Xiayi Liu
- Department of Prosthodontics, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - Hualing Sun
- Department of Prosthodontics, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - Miao Yu
- Department of Prosthodontics, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - Jie Liu
- Department of Prosthodontics, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - Beining Yang
- Department of Prosthodontics, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - Yanru Wu
- Department of Prosthodontics, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
| | - Jiawei Wang
- Department of Prosthodontics, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
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25
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He XT, Wu RX, Xu XY, Wang J, Yin Y, Chen FM. Macrophage involvement affects matrix stiffness-related influences on cell osteogenesis under three-dimensional culture conditions. Acta Biomater 2018; 71:132-147. [PMID: 29462712 DOI: 10.1016/j.actbio.2018.02.015] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 01/29/2018] [Accepted: 02/12/2018] [Indexed: 12/16/2022]
Abstract
Accumulating evidence indicates that the physicochemical properties of biomaterials exert profound influences on stem cell fate decisions. However, matrix-based regulation selected through in vitro analyses based on a given cell population do not genuinely reflect the in vivo conditions, in which multiple cell types are involved and interact dynamically. This study constitutes the first investigation of how macrophages (Mφs) in stiffness-tunable transglutaminase cross-linked gelatin (TG-gel) affect the osteogenesis of bone marrow-derived mesenchymal stem cells (BMMSCs). When a single cell type was cultured, low-stiffness TG-gels promoted BMMSC proliferation, whereas high-stiffness TG-gels supported cell osteogenic differentiation. However, Mφs in high-stiffness TG-gels were more likely to polarize toward the pro-inflammatory M1 phenotype. Using either conditioned medium (CM)-based incubation or Transwell-based co-culture, we found that Mφs encapsulated in the low-stiffness matrix exerted a positive effect on the osteogenesis of co-cultured BMMSCs. Conversely, Mφs in high-stiffness TG-gels negatively affected cell osteogenic differentiation. When both cell types were cultured in the same TG-gel type and placed into the Transwell system, the stiffness-related influences of Mφs on BMMSCs were significantly altered; both the low- and high-stiffness matrix induced similar levels of BMMSC osteogenesis. Although the best material parameter for synergistically affecting Mφs and BMMSCs remains unknown, our data suggest that Mφ involvement in the co-culture system alters previously identified material-related influences on BMMSCs, such as matrix stiffness-related effects, which were identified based on a culture system involving a single cell type. Such Mφ-stem cell interactions should be considered when establishing proper matrix parameter-associated cell regulation in the development of biomimetic biomaterials for regenerative applications. STATEMENT OF SIGNIFICANCE The substrate stiffness of a scaffold plays critical roles in modulating both reparative cells, such as mesenchymal stem cells (MSCs), and immune cells, such as macrophages (Mφs). Although the influences of material stiffness on either Mφs or MSCs, have been extensively described, how the two cell types respond to matrix cues to dynamically affect each other in a three-dimensional (3D) biosystem remains largely unknown. Here, we report our findings that, in a platform wherein Mφs and bone marrow-derived MSCs coexist, matrix stiffness can influence stem cell fate through both direct matrix-associated regulation and indirect Mφ-based modulation. Our data support future studies of the MSC-Mφ-matrix interplay in the 3D context to optimize matrix parameters for the development of the next biomaterial.
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Li X, He X, Yin Y, Wu R, Tian B, Chen F. Administration of signalling molecules dictates stem cell homing for in situ regeneration. J Cell Mol Med 2017; 21:3162-3177. [PMID: 28767189 PMCID: PMC5706509 DOI: 10.1111/jcmm.13286] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2017] [Accepted: 05/29/2017] [Indexed: 12/13/2022] Open
Abstract
Ex vivo-expanded stem cells have long been a cornerstone of biotherapeutics and have attracted increasing attention for treating intractable diseases and improving tissue regeneration. However, using exogenous cellular materials to develop restorative treatments for large numbers of patients has become a major concern for both economic and safety reasons. Advances in cell biological research over the past two decades have expanded the potential for using endogenous stem cells during wound healing processes, and in particular, recent insight into stem cell movement and homing has prompted regenerative research and therapy based on recruiting endogenous cells. Inspired by the natural healing process, artificial administration of specific chemokines as signals systemically or at the injury site, typically using biomaterials as vehicles, is a state-of-the-art strategy that potentiates stem cell homing and recreates an anti-inflammatory and immunomodulatory microenvironment to enhance in situ tissue regeneration. However, pharmacologically coaxing endogenous stem cells to act as therapeutics in the field of biomedicine remains in the early stages; its efficacy is limited by the lack of innovative methodologies for chemokine presentation and release. This review describes how to direct the homing of endogenous stem cells via the administration of specific signals, with a particular emphasis on targeted signalling molecules that regulate this homing process, to enhance in situ tissue regeneration. We also provide an outlook on and critical considerations for future investigations to enhance stem cell recruitment and harness the reparative potential of these recruited cells as a clinically relevant cell therapy.
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Affiliation(s)
- Xuan Li
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral DiseasesDepartment of PeriodontologySchool of StomatologyFourth Military Medical UniversityXi'anChina
| | - Xiao‐Tao He
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral DiseasesDepartment of PeriodontologySchool of StomatologyFourth Military Medical UniversityXi'anChina
| | - Yuan Yin
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral DiseasesDepartment of PeriodontologySchool of StomatologyFourth Military Medical UniversityXi'anChina
| | - Rui‐Xin Wu
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral DiseasesDepartment of PeriodontologySchool of StomatologyFourth Military Medical UniversityXi'anChina
| | - Bei‐Min Tian
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral DiseasesDepartment of PeriodontologySchool of StomatologyFourth Military Medical UniversityXi'anChina
| | - Fa‐Ming Chen
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral DiseasesDepartment of PeriodontologySchool of StomatologyFourth Military Medical UniversityXi'anChina
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27
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Yin Y, Wu RX, He XT, Xu XY, Wang J, Chen FM. Influences of age-related changes in mesenchymal stem cells on macrophages during in-vitro culture. Stem Cell Res Ther 2017; 8:153. [PMID: 28646912 PMCID: PMC5483296 DOI: 10.1186/s13287-017-0608-0] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2017] [Accepted: 06/08/2017] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) have been widely used in cytotherapy and tissue engineering due to their immunosuppressive ability and regenerative potential. Recently, the immunomodulatory influence of MSCs has been gaining increasing attention because their functional roles in modulating immune responses likely have high clinical significance. METHODS In this study, we investigated the influence of MSCs on macrophages (Mφs) in in-vitro cell culture systems. Given evidence that aged MSCs are functionally compromised, bone marrow-derived MSCs (BMSCs) isolated from both young and aged mice (YMSCs and AMSCs) were evaluated and contrasted. RESULTS We found that YMSCs exhibited greater proliferative and osteo-differentiation potential compared to AMSCs. When cocultured with RAW264.7 cells (an Mφ cell line), both YMSCs and AMSCs coaxed polarization of Mφs toward an M2 phenotype and induced secretion of anti-inflammatory and immunomodulatory cytokines. Compared to AMSCs, YMSCs exhibited a more potent immunomodulatory effect. While Mφs cocultured with either YMSCs or AMSCs displayed similar phagocytic ability, AMSC coculture was found to enhance Mφ migration in Transwell systems. When BMSCs were prestimulated with interferon gamma before coculture with RAW264.7 cells, their regulatory effects on Mφs appeared to be modified. Here, compared to stimulated AMSCs, stimulated YMSCs also exhibited enhanced cellular influence on cocultured RAW264.7 cells. CONCLUSIONS Our data suggest that BMSCs exert an age-related regulatory effect on Mφs with respect to their phenotype and functions but an optimized stimulation to enhance MSC immunomodulation is in need of further investigation.
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Affiliation(s)
- Yuan Yin
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 145th West Changle Road, Xi’an, 710032 People’s Republic of China
| | - Rui-Xin Wu
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 145th West Changle Road, Xi’an, 710032 People’s Republic of China
| | - Xiao-Tao He
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 145th West Changle Road, Xi’an, 710032 People’s Republic of China
| | - Xin-Yue Xu
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 145th West Changle Road, Xi’an, 710032 People’s Republic of China
| | - Jia Wang
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 145th West Changle Road, Xi’an, 710032 People’s Republic of China
| | - Fa-Ming Chen
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 145th West Changle Road, Xi’an, 710032 People’s Republic of China
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28
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Yu Y, Yin Y, Wu RX, He XT, Zhang XY, Chen FM. Hypoxia and low-dose inflammatory stimulus synergistically enhance bone marrow mesenchymal stem cell migration. Cell Prolif 2016; 50. [PMID: 27679423 DOI: 10.1111/cpr.12309] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Accepted: 09/11/2016] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES Cell migration is necessary for numerous physiological cell processes. Although either inflammatory or hypoxic stimuli of certain dose and duration have positive influence on cell migration, their combination has not been shown to result in a synergistic effect. MATERIALS AND METHODS In this study, we investigated combined effects of hypoxia and low-dose inflammatory stimulus (one-tenth of that of a previously used concentration) on migration of human bone marrow-derived mesenchymal stem cells (BMMSCs). RESULTS Our results from real-time PCR, Western blot analysis and an immunofluorescence assay, showed that dual stimulation up-regulated CXCR4 expression. Based on tablet scratch experimentation and transwell assay, the dual stimuli exhibited greater positive effects on cell migration than a single inflammatory or hypoxic stimulus. When effects of various pre-treatments on cell proliferation, differentiation and immunosuppression were screened, cells subjected to the hypoxic stimulus or dual stimuli had increased cell proliferation, while short-term inflammatory stimulus and/or hypoxic stimulus had no negative effect on cell differentiation and immunosuppression. CONCLUSIONS These findings suggest that the combination of hypoxia and low-dose inflammatory stimuli enhances the potential of BMMSCs to migrate, thus identifying cell pre-treatment conditions that could enhance future stem cell-based therapeutics.
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Affiliation(s)
- Yang Yu
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.,Department of Stomatology, Jinan Military General Hospital, Jinan, Shandong Province, China
| | - Yuan Yin
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Rui-Xin Wu
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Xiao-Tao He
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Xi-Yu Zhang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Fa-Ming Chen
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China
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