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Liu J, Dai G, Xiao L, Rui Y. Tendon-Derived Stem Cell Sheet Promotes Early-Stage Tendon-Bone Healing. JOURNAL OF MUSCULOSKELETAL & NEURONAL INTERACTIONS 2025; 25:133-141. [PMID: 40024236 PMCID: PMC11880849 DOI: 10.22540/jmni-25-133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/08/2024] [Indexed: 03/04/2025]
Abstract
OBJECTIVES To investigate the role of a tendon-derived stem cell (TDSC) sheet in tendon-bone healing within an extra-articular bone tunnel rat model. METHODS Sprague-Dawley rats were randomly assigned to experimental and control groups. The superficial flexor tendon, with or without a TDSC sheet, was transplanted into a 1.0-mm diameter bone tunnel in the proximal tibia. The impact of the TDSC sheet on tendon-bone healing was assessed through radiological analysis, histological staining, and biomechanical testing. RESULTS The TDSC sheet significantly enhanced tendon-bone healing, as evidenced by higher tunnel bone mineral density and bone volume/total volume at 4 weeks post-operation. Hematoxylin-eosin staining revealed that the TDSC sheet promoted the alignment of perpendicular collagen fibers connecting the tendon to the bone, along with Sharpey's fibers and new bone formation at the tendon-bone junction at both 4 and 8 weeks. Additionally, Masson's staining demonstrated that the tendon-bone interface was filled with abundant collagen fibers, with a significantly higher proportion of collagen fiber area in the TDSC sheet group compared to the control group at both 4 and 8 weeks. CONCLUSION The TDSC sheet may enhance tendon-bone healing in the early stages, providing a potential therapeutic approach to accelerate tendon-bone remodeling.
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Affiliation(s)
- Junyan Liu
- Department of Joint Surgery, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China
- Department of Orthopedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, PR China
- School of Medicine, Southeast University, Nanjing, Jiangsu, PR China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, Jiangsu, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, PR China
| | - Guangchun Dai
- Department of Orthopedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, PR China
- School of Medicine, Southeast University, Nanjing, Jiangsu, PR China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, Jiangsu, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, PR China
| | - Longfei Xiao
- Department of Orthopedics, Sheyang County People’s Hospital, Yancheng, Jiangsu, PR China
| | - Yunfeng Rui
- Department of Orthopedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, PR China
- School of Medicine, Southeast University, Nanjing, Jiangsu, PR China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, Jiangsu, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, PR China
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Cho GH, Bae HC, Lee YJ, Yang HR, Kang H, Park HJ, Wang SY, Kim YJ, Kang HS, Kim IG, Choi BS, Han HS. Insulin-Like Growth Factor 2 Secreted from Mesenchymal Stem Cells with High Glutathione Levels Alleviates Osteoarthritis via Paracrine Rejuvenation of Senescent Chondrocytes. Biomater Res 2025; 29:0152. [PMID: 39990979 PMCID: PMC11842674 DOI: 10.34133/bmr.0152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 01/22/2025] [Accepted: 01/31/2025] [Indexed: 02/25/2025] Open
Abstract
Senescent chondrocytes, which are increased in osteoarthritic (OA) cartilage, promote cartilage defects and the senescent knee microenvironment by inducing senescence to surrounding normal chondrocytes by secreting senescence-associated secretory proteins. Many studies have used mesenchymal stem cells (MSCs) to treat OA, but MSC treatment remains challenging for clinical application owing to MSC quality control, engraftment, and fibrocartilage regeneration. Here, rather than relying on the direct regeneration of MSCs, we present a novel strategy to suppress OA by MSC-mediated senescent chondrocyte targeting via the paracrine activity of MSCs, thereby improving the knee microenvironment. First, to enable quality control of umbilical cord MSCs, priming MSCs by supplementing human platelet lysate (hPL) greatly enhanced MSC functions by increasing cellular glutathione levels throughout serial passaging. Intra-articular injection of primed MSCs successfully suppressed OA progression and senescent chondrocyte accumulation without direct regeneration. Indirect coculture with primed MSCs using transwell ameliorated the senescence phenotypes in OA chondrocytes, suggesting paracrine rejuvenation. Based on secretome analysis, we identified insulin-like growth factor 2 (IGF2) as a key component that induces paracrine rejuvenation by primed MSCs. The rejuvenation effects of IGF2 act through autophagy activation through the up-regulation of autophagy-related gene expression and autophagic flux. To cross-validate the effects of secreted IGF2 in vivo, knockdown of IGF2 in primed MSCs substantially abolished its therapeutic efficacy in a rabbit OA model. Collectively, these findings demonstrate that hPL supplementation enables MSC quality control by increasing MSC glutathione levels. The therapeutic mechanism of primed MSCs was secreted IGF2, which induces paracrine rejuvenation of senescent OA chondrocytes by activating autophagy.
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Affiliation(s)
- Gun Hee Cho
- Interdisciplinary Programs: Stem Cell Biology, College of Medicine,
Seoul National University, Seoul 03080, Korea
- Department of Orthopedic Surgery, College of Medicine,
Seoul National University, Seoul 03080, Korea
| | - Hyun Cheol Bae
- Department of Orthopedic Surgery,
Seoul National University Hospital, Seoul 110-744, Korea
| | - Yu Jeong Lee
- Department of Orthopedic Surgery,
Seoul National University Hospital, Seoul 110-744, Korea
| | - Ha Ru Yang
- Department of Orthopedic Surgery,
Seoul National University Hospital, Seoul 110-744, Korea
| | - Hyewon Kang
- Laboratory for Cellular Response to Oxidative Stress, Cell2in Inc., Seoul 03127, Korea
| | - Hee Jung Park
- Department of Orthopedic Surgery,
Seoul National University Hospital, Seoul 110-744, Korea
| | - Sun Young Wang
- Department of Orthopedic Surgery,
Seoul National University Hospital, Seoul 110-744, Korea
| | - You Jung Kim
- Department of Orthopedic Surgery,
Seoul National University Hospital, Seoul 110-744, Korea
| | - Heun-Soo Kang
- Laboratory for Cellular Response to Oxidative Stress, Cell2in Inc., Seoul 03127, Korea
| | - In Gyu Kim
- Laboratory for Cellular Response to Oxidative Stress, Cell2in Inc., Seoul 03127, Korea
| | - Byung Sun Choi
- Department of Orthopedic Surgery,
Seoul National University Hospital, Seoul 110-744, Korea
| | - Hyuk-Soo Han
- Interdisciplinary Programs: Stem Cell Biology, College of Medicine,
Seoul National University, Seoul 03080, Korea
- Department of Orthopedic Surgery, College of Medicine,
Seoul National University, Seoul 03080, Korea
- Department of Orthopedic Surgery,
Seoul National University Hospital, Seoul 110-744, Korea
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Samiei M, Harmsen MC, Abdolahinia ED, Barar J, Petridis X. Scaffold-Free Strategies in Dental Pulp/Dentine Tissue Engineering: Current Status and Implications for Regenerative Biological Processes. Bioengineering (Basel) 2025; 12:198. [PMID: 40001717 PMCID: PMC11851408 DOI: 10.3390/bioengineering12020198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 02/16/2025] [Accepted: 02/17/2025] [Indexed: 02/27/2025] Open
Abstract
Conventionally, root canal treatment is performed when the dental pulp is severely damaged or lost due to dental trauma or bacterial endodontic infections. This treatment involves removing the compromised or infected pulp tissue, disinfecting the root canal system, and sealing it with inert, non-degradable materials. However, contemporary endodontic treatment has shifted from merely obturating the root canal system with inert materials to guiding endodontic tissue regeneration through biological approaches. The ultimate goal of regenerative endodontics is to restore dental pulp tissue with structural organization and functional characteristics akin to the native pulp, leveraging advancements in tissue engineering and biomaterial sciences. Dental pulp tissue engineering commonly employs scaffold-based strategies, utilizing biomaterials as initial platforms for cell and growth factor delivery, which subsequently act as scaffolds for cell proliferation, differentiation and maturation. However, cells possess an intrinsic capacity for self-organization into spheroids and can generate their own extracellular matrix, eliminating the need for external scaffolds. This self-assembling property presents a promising alternative for scaffold-free dental pulp engineering, addressing limitations associated with biomaterial-based approaches. This review provides a comprehensive overview of cell-based, self-assembling and scaffold-free approaches in dental pulp tissue engineering, highlighting their potential advantages and challenges in advancing regenerative endodontics.
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Affiliation(s)
- Mohammad Samiei
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands; (M.S.); (M.C.H.)
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran
| | - Martin Conrad Harmsen
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands; (M.S.); (M.C.H.)
| | - Elaheh Dalir Abdolahinia
- Department of Oral Science and Translation Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA;
| | - Jaleh Barar
- Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA;
| | - Xenos Petridis
- Department of Endodontics, Section of Dental Pathology & Therapeutics, School of Dentistry, National and Kapodistrian University of Athens, 115 27 Athens, Greece
- Department of Endodontology, Section of Fundamental Dentistry, Center for Dentistry and Oral Hygiene, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
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Guo J, Ouyang XY, Liu JR, Liu WY, Wang YB. miR-508-5p suppresses osteogenic differentiation of human periodontal ligament stem cells via targeting sex-determining region Y-related HMG-box 11. J Dent Sci 2025; 20:201-211. [PMID: 39873049 PMCID: PMC11763229 DOI: 10.1016/j.jds.2024.08.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Revised: 08/19/2024] [Indexed: 01/30/2025] Open
Abstract
Background/Purpose The local inflammatory microenvironment created by periodontitis negatively impacts periodontal tissue regeneration, necessitating the development of methods to enhance the regenerative capacity of stem cells. This study explored the regulatory role and underlying mechanism of miR-508-5p in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Materials and methods The regulatory roles of miR-508-5p in osteogenic differentiation of hPDLSCs were investigated through its inhibition or overexpression. Expression of the sex-determining region Y-related HMG-box 11 (SOX11) and osteogenic markers was analyzed using Western blot and real-time PCR. Osteogenesis was measured using alizarin red S (ARS) staining and alkaline phosphatase (ALP) staining. A dual luciferase reporter assay was performed to confirm SOX11 as a target of miR-508-5p. Results During the osteogenic differentiation of hPDLSCs, miR-508-5p expression level gradually decreased, while that of SOX11 increased. miR-508-5p inhibition significantly promoted osteogenesis in hPDLSCs, while overexpression inhibited the process. SOX11 overexpression reversed the suppressive effects of miR-508-5p on the osteogenic differentiation of hPDLSCs. miR-508-5p downregulation significantly increased SOX11; a dual luciferase reporter assay provided evidence for their direct targeting. Conclusion miR-508-5p downregulation promotes the osteogenic differentiation of hPDLSCs by targeting SOX11.
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Affiliation(s)
- Jing Guo
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentisitry Minisrty of Health, Beijing, China
| | - Xiang-Ying Ouyang
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentisitry Minisrty of Health, Beijing, China
| | - Jian-Ru Liu
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentisitry Minisrty of Health, Beijing, China
| | - Wen-Yi Liu
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentisitry Minisrty of Health, Beijing, China
| | - Yuan-Bo Wang
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentisitry Minisrty of Health, Beijing, China
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Wen S, Zheng X, Yin W, Liu Y, Wang R, Zhao Y, Liu Z, Li C, Zeng J, Rong M. Dental stem cell dynamics in periodontal ligament regeneration: from mechanism to application. Stem Cell Res Ther 2024; 15:389. [PMID: 39482701 PMCID: PMC11526537 DOI: 10.1186/s13287-024-04003-9] [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: 08/21/2024] [Accepted: 10/17/2024] [Indexed: 11/03/2024] Open
Abstract
Periodontitis, a globally prevalent chronic inflammatory disease is characterized by the progressive degradation of tooth-supporting structures, particularly the periodontal ligament (PDL), which can eventually result in tooth loss. Despite the various clinical interventions available, most focus on symptomatic relief and lack substantial evidence of supporting the functional regeneration of the PDL. Dental stem cells (DSCs), with their homology and mesenchymal stem cell (MSC) properties, have gained significant attention as a potential avenue for PDL regeneration. Consequently, multiple therapeutic strategies have been developed to enhance the efficacy of DSC-based treatments and improve clinical outcomes. This review examines the mechanisms by which DSCs and their derivatives promote PDL regeneration, and explores the diverse applications of exogenous implantation and endogenous regenerative technology (ERT) aimed at amplifying the regenerative capacity of endogenous DSCs. Additionally, the persistent challenges and controversies surrounding DSC therapies are discussed, alongside an evaluation of the limitations in current research on the underlying mechanisms and innovative applications of DSCs in PDL regeneration with the aim of providing new insights for future development. Periodontitis, a chronic inflammatory disease, represents a major global public health concern, affecting a significant proportion of the population and standing as the leading cause tooth loss in adults. The functional periodontal ligament (PDL) plays an indispensable role in maintaining periodontal health, as its structural and biological integrity is crucial for the long-term prognosis of periodontal tissues. It is widely recognized as the cornerstone of periodontal regeneration Despite the availability of various treatments, ranging from nonsurgical interventions to guided tissue regeneration (GTR) techniques, these methods have shown limited success in achieving meaningful PDL regeneration. As a result, the inability to fully restore PDL function underscores the urgent need for innovative therapeutic strategies at reconstructing this essential structure. Stem cell therapy, known for its regenerative and immunomodulatory potential, offers a promising approach for periodontal tissue repair. Their application marks a significant paradigm shift in the treatment of periodontal diseases, opening new avenues for functional PDL regeneration. However, much of the current research has primarily focused on the regeneration of alveolar bone and gingiva, as these hard and soft tissues can be more easily evaluated through visual assessment. The complexity of PDL structure, coupled with the intricate interactions among cellular and molecular components, presents significant scientific and clinical hurdles in translating DSC research into practical therapeutic applications. This review provides a thorough exploration of DSC dynamics in periodontal regeneration, detailing their origins, properties, and derived products, while also examining their potential mechanisms and applications in PDL regeneration. It offers an in-depth analysis of the current research, landscape, acknowledging both the progress made and the challenges that remain in bridging the gap between laboratory findings and clinical implementation. Finally, the need for continued investigation into the intricate mechanisms governing DSC behavior and the optimization of their use in regenerative therapies for periodontal diseases is also emphasized.
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Affiliation(s)
- Shuyi Wen
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China
| | - Xiao Zheng
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China
| | - Wuwei Yin
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China
| | - Yushan Liu
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China
| | - Ruijie Wang
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China
| | - Yaqi Zhao
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China
| | - Ziyi Liu
- Department of Stomatology, Shunde Hospital, Southern Medical University, The First People's Hospital of Shunde, Foshan, Guangdong, 528308, China
| | - Cong Li
- Dongguan Key Laboratory of Metabolic Immunology and Oral Diseases, Dongguan Maternal and Child Health Care Hospital, Dongguan, Guangdong, 523000, China
| | - Jincheng Zeng
- Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, Guangdong Medical University, Dongguan, Guangdong, 523808, China.
| | - Mingdeng Rong
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China.
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Safi IN, Hussein BMA, Al-Khafaji AM, Fatalla AA, Al-Shammari AM. Evaluation of Random and Aligned Polycaprolactone Nanofibrous Electrospun Scaffold for Human Periodontal Ligament Engineering in Biohybrid Titanium Implants. Int J Dent 2024; 2024:2571976. [PMID: 39450145 PMCID: PMC11502134 DOI: 10.1155/2024/2571976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 10/05/2023] [Accepted: 09/23/2024] [Indexed: 10/26/2024] Open
Abstract
Background: Stem cells are introduced to regenerate some living tissue to restore function and longevity. The study aims to isolate in vitro human periodontal ligament stem cells (hPDLSCs) and investigate their proliferation rate on plasma-treated aligned and random polycaprolactone (PCL) nanofibrous scaffolds made via an electrospinning technique to attempt periodontal-like tissue in dental implants. Materials and Methods: hPDLSCs were isolated from extracted human premolars and cultured on plasma-treated or untreated PCL-aligned and random scaffolds to enhance adhesion of periodontal ligament (PDL) cells as well as interaction and proliferation. Cell morphology, adhesion, and proliferation rate were evaluated using field emission scanning electron microscopy (FESEM) and the methyl tetrazolium (MTT) assay. The wettability of PCL scaffolds was tested using a goniometer. Results: The hydrophilicity of plasma-treated scaffolds was significantly increased (p ≤ 0.05) in both aligned and random nanofibers compared to the nontreated nanofibrous scaffold. Cells arranged in different directions on the random nanofiber scaffold, while for aligned scaffold nanofibers, the cells were arranged in a pattern that followed the direction of the aligned electrospun nanofibres. The rate of hPDLSC proliferation on an aligned PCL nanofiber scaffold was significantly higher than on a random PCL nanofibrous scaffold with a continuous, well-arranged monolayer of cells, as shown in FESEM. Conclusion: The aligned PCL nanofiber scaffold is superior to random PCL when used as an artificial scaffold for hPDLSC regeneration in PDL tissue engineering applications.
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Affiliation(s)
- Ihab N. Safi
- Department of Prosthodontics, College of Dentistry, University of Baghdad, Baghdad, Iraq
| | - Basima Mohammed Ali Hussein
- Department of Biomedical Applications, Institute of Laser for Postgraduate Studies, University of Baghdad, Baghdad, Iraq
| | | | - Abdalbseet A. Fatalla
- Department of Prosthodontics, College of Dentistry, University of Baghdad, Baghdad, Iraq
| | - Ahmed M. Al-Shammari
- Experimental Therapy Department, Iraqi Center for Cancer and Medical Genetic Research, Mustansiriyah University, Baghdad, Iraq
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Hu D, Gao C, Li J, Tong P, Sun Y. The preparation methods and types of cell sheets engineering. Stem Cell Res Ther 2024; 15:326. [PMID: 39334404 PMCID: PMC11438047 DOI: 10.1186/s13287-024-03937-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 09/12/2024] [Indexed: 09/30/2024] Open
Abstract
Cell therapy has emerged as a viable approach for treating damaged organs or tissues, particularly with advancements in stem cell research and regenerative medicine. The innovative technique of cell sheet engineering offers the potential to create a cell-dense lamellar structure that preserves the extracellular matrix (ECM) secreted by cells, along with the cell-matrix and intercellular junctions formed during in vitro cultivation. In recent years, significant progress has been made in developing cell sheet engineering technology. A variety of novel materials and methods were utilized for enzyme-free cell detachment during the cell sheet formation process. The complexity of cell sheet structures increased to meet advanced usage demands. This review aims to provide an overview of the preparation methods and types of cell sheets, thereby enhancing the understanding of this rapidly evolving technology and offering a fresh perspective on the development and future application of cell sheet engineering.
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Affiliation(s)
- Danping Hu
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China
- Hangzhou Chexmed Technology Co., Ltd, Hangzhou, China
| | - Ce Gao
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China
| | - Jie Li
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China
| | - Pei Tong
- Hunan Guangxiu Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Yi Sun
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China.
- National Engineering and Research Center of Human Stem Cells, Changsha, China.
- Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, Changsha, China.
- Hunan Guangxiu Affiliated Hospital of Hunan Normal University, Changsha, China.
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Kanda T, Iwasaki K, Taguchi Y, Umeda M. Role of sodium-dependent vitamin C transporter 2 in human periodontal ligament fibroblasts. J Periodontal Res 2024. [PMID: 39225294 DOI: 10.1111/jre.13322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 06/19/2024] [Accepted: 06/21/2024] [Indexed: 09/04/2024]
Abstract
AIM Ascorbic acid (AA) is a water-soluble vitamin that has antioxidant properties and regulates homeostasis of connective tissue through controlling various enzymatic activities. Two cell surface glycoproteins, sodium-dependent vitamin C transporter (SVCT) 1 and SVCT2, are known as ascorbate transporters. The purpose of this study was to investigate the expression pattern and functions of SVCTs in periodontal ligament (PDL) and PDL fibroblast (PDLF). METHODS Gene expression was examined using real-time polymerase chain reaction (PCR) and reverse transcription PCR. SVCT2 expression was determined by immunofluorescence staining, western blot and flow cytometry. ALP activity and collagen production were examined using ALP staining and collagen staining. Short interfering RNA was used to knock down the gene level of SVCT2. Change of comprehensive gene expression under SVCT2 knockdown condition was examined by RNA-sequencing analysis. RESULTS Real-time PCR, fluorescent immunostaining, western blot and flowy cytometry showed that SVCT2 was expressed in PDLF and PDL. ALP activity, collagen production, and SVCT2 expression were enhanced upon AA stimulation in PDLF. The enhancement of ALP activity, collagen production, and SVCT2 expression by AA was abolished under SVCT2 knockdown condition. RNA-sequencing revealed that gene expression of CLDN4, Cyclin E2, CAMK4, MSH5, DMC1, and Nidgen2 were changed by SVCT2 knockdown. Among them, the expression of MSH5 and DMC1, which are related to DNA damage sensor activity, was enhanced by AA, suggesting the new molecular target of AA in PDLF. CONCLUSION Our study reveals the SVCT2 expression in PDL and the pivotal role of SVCT2 in mediating AA-induced enhancements of ALP activity and collagen production in PDLF. Additionally, we identify alterations in gene expression profiles, highlighting potential molecular targets influenced by AA through SVCT2. These findings deepen our understanding of periodontal tissue homeostasis mechanisms and suggest promising intervention targeting AA metabolism.
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Affiliation(s)
- Tomoko Kanda
- Graduate School of Dentistry (Department of Periodontology), Osaka Dental University, Osaka, Japan
| | - Kengo Iwasaki
- Division of Creative and Integrated Medicine, Advanced Medicine Research Center, Translational Research Institute for Medical Innovation (TRIMI), Osaka Dental University, Osaka, Japan
| | - Yoichiro Taguchi
- Department of Periodontology, Osaka Dental University, Osaka, Japan
| | - Makoto Umeda
- Department of Periodontology, Osaka Dental University, Osaka, Japan
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Gasparoni LM, Alves T, França BND, Balzarini D, Albuquerque-Souza E, Pedroni ACF, Rovai EDS, Mendoza AH, Sipert CR, Holzhausen M. Cell sheet produced from periodontal ligament stem cells activated by PAR1 improves osteogenic differentiation. Braz Oral Res 2024; 38:e079. [PMID: 39258632 PMCID: PMC11376637 DOI: 10.1590/1807-3107bor-2024.vol38.0079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 04/23/2024] [Accepted: 04/02/2024] [Indexed: 09/12/2024] Open
Abstract
Periodontal regeneration is a challenge, and tissue engineering based on periodontal ligament stem cells (PDLSCs) has been shown to be a promising alternative to this process. However, the need for scaffolds has limited the therapeutic use of PDLSCs. In this context, scaffold-free tissue engineering using the cell sheet (CS) technique has been developed as an alternative approach to improve tissue regeneration. Previously, we showed that Protease-activated receptor-1 (PAR1) can regulate PDLSCs. Herein, we evaluate whether PAR1 influences osteogenesis in CSs produced from PDLSCs, without the use of scaffolds. PDLSCs were isolated and immunophenotyped. Then, CSs were obtained by supplementing the culture medium with ascorbic acid (50 µg/mL), and PAR1 was activated through its agonist peptide (100 nM). Scaffold-free 3D CSs were successfully produced from PDLSCs, and they showed higher proliferation potential than isolated PDLSCs. Also, PAR1 activation decreased senescence and improved osteogenic differentiation of CSs by increasing mineralized nodule deposition and alkaline phosphatase concentration; PAR1 also modulated osteogenic markers at the gene and protein levels. We further demonstrated that this effect was regulated by Wnt, TGF-βI, MEK, p38 MAPK, and FGF/VEGF signaling pathways in PDLSCs (p < 0.05%). Overall, PAR1 activation increased osteogenic activity in CSs, emerging as a promising scaffold-free therapeutic approach for periodontal regeneration.
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Affiliation(s)
- Letícia Miquelitto Gasparoni
- Universidade Federal de Juiz de Fora - UFJF, School of Dentistry, Department of Dental Clinic, Juiz de Fora, MG, Brazil
| | - Tomaz Alves
- University of North Carolina, Adams School of Dentistry, Division of Comprehensive Oral Health, Chapel Hill, NC, USA
| | - Bruno Nunes de França
- Universidade São Francisco - USF, School of Dentistry, Bragança Paulista, SP, Brazil
| | - Danilo Balzarini
- Universidade de São Paulo - USP, School of Dentistry, Department of Stomatology, São Paulo, SP, Brazil
| | | | - Ana Clara Fagundes Pedroni
- Universidade de São Paulo - USP, School of Dentistry, Department of Restorative Dentistry, São Paulo, SP, Brazil
| | - Emanuel da Silva Rovai
- Universidade Estadual Paulista - Unesp, Institute of Science and Technology, Division of Periodontics, São José dos Campos, SP, Brazil
| | - Aldrin Huamán Mendoza
- Universidade de São Paulo - USP, School of Dentistry, Department of Stomatology, São Paulo, SP, Brazil
| | - Carla Renata Sipert
- Universidade de São Paulo - USP, School of Dentistry, Department of Restorative Dentistry, São Paulo, SP, Brazil
| | - Marinella Holzhausen
- Universidade de São Paulo - USP, School of Dentistry, Department of Stomatology, São Paulo, SP, Brazil
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Ma Z, Wang J, Li L, Wang S, Hu L, Wang H. LIM homeobox 8 reduced apoptosis and promoted periodontal tissue regeneration function of dental pulp stem cells. Tissue Cell 2024; 88:102387. [PMID: 38703583 DOI: 10.1016/j.tice.2024.102387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 03/27/2024] [Accepted: 04/16/2024] [Indexed: 05/06/2024]
Abstract
Stem cell-mediated tissue regeneration is a promising strategy for repairing tissue defects and functional reconstruction in periodontitis, a common disease that leads to the loss of alveolar bone and teeth. However, stem cell apoptosis, widely observed during tissue regeneration, impairs its efficiency. Therefore, the regulation of stem cell apoptosis is critical for improving regeneration efficiency. The LIM homeobox 8 gene LHX8, belongs to the LIM homeobox family, which was involved in tooth morphogenesis. Here, we found that LHX8 was significantly expressed in dental pulp. LHX8 knockdown significantly increased dental pulp mesenchymal stem cells (DPSCs) apoptosis, as confirmed by RT-PCR, western blotting, flow cytometry, and transmission electron microscopy. Additionally, LHX8 overexpression inhibited apoptosis and enhanced the osteo/odontogenic differentiation potential of hDPSCs in vitro. Furthermore, LHX8-overexpression could enhance the periodontal tissue regeneration efficiency of hDPSCs in mice with periodontitis. In conclusion, the present study indicates that LHX8 inhibits stem cell apoptosis and promotes functional tissue formation in stem cell-based tissue regeneration engineering, suggesting a new therapeutic target to increase the efficacy of periodontal tissue regeneration.
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Affiliation(s)
- Zhiyu Ma
- Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and School of Stomatology, Capital Medical University, Beijing 100050, China; Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medicine, Beijing, China
| | - Jinsong Wang
- Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medicine, Beijing, China
| | - Le Li
- Department of Stomatology, Tsinghua University Hospital, Beijing 100069, China
| | - Songlin Wang
- Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and School of Stomatology, Capital Medical University, Beijing 100050, China; Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medicine, Beijing, China.
| | - Lei Hu
- Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and School of Stomatology, Capital Medical University, Beijing 100050, China.
| | - Haifeng Wang
- Department of Stomatology, Beijing Bo'ai Hospital, China Rehabilitation Research Center, School of Rehabilitation, Capital Medical University, Beijing 100068, China.
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11
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Anitua E, Troya M, Zalduendo M, Tierno R, Alkhraisat MH, Osinalde N, Fullaondo A, Zubiaga AM. Improving the mechanical and biological functions of cell sheet constructs: The interplay of human-derived periodontal ligament stem cells, endothelial cells and plasma rich in growth factors. Biomed Pharmacother 2024; 174:116599. [PMID: 38640711 DOI: 10.1016/j.biopha.2024.116599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 04/02/2024] [Accepted: 04/11/2024] [Indexed: 04/21/2024] Open
Abstract
OBJECTIVE The aim of this study was to produce and characterize triple-layered cell sheet constructs with varying cell compositions combined or not with the fibrin membrane scaffold obtained by the technology of Plasma Rich in Growth Factors (mPRGF). MATERIALS AND METHODS Human primary cultures of periodontal ligament stem cells (hPDLSCs) were isolated, and their stemness nature was evaluated. Three types of triple-layered composite constructs were generated, composed solely of hPDLSCs or combined with human umbilical vein endothelial cells (HUVECs), either as a sandwiched endothelial layer or as coculture sheets of both cell phenotypes. These three triple-layered constructs were also manufactured using mPRGF as cell sheets' support. Necrosis, glucose consumption, secretion of extracellular matrix proteins and synthesis of proangiogenic factors were determined. Histological evaluations and proteomic analyses were also performed. RESULTS The inclusion of HUVECs did not clearly improve the properties of the multilayered constructs and yet hindered their optimal conformation. The presence of mPRGF prevented the shrinkage of cell sheets, stimulated the metabolic activity and increased the matrix synthesis. At the proteome level, mPRGF conferred a dramatic advantage to the hPDLSC constructs in their ability to provide a suitable environment for tissue regeneration by inducing the expression of proteins necessary for bone morphogenesis and cellular proliferation. CONCLUSIONS hPDLSCs' triple-layer construct onto mPRGF emerges as the optimal structure for its use in regenerative therapeutics. CLINICAL RELEVANCE These results suggest the suitability of mPRGF as a promising tool to support cell sheet formation by improving their handling and biological functions.
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Affiliation(s)
- Eduardo Anitua
- BTI-Biotechnology Institute, Vitoria, Spain; University Institute for Regenerative Medicine & Oral Implantology, UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria, Spain.
| | - María Troya
- BTI-Biotechnology Institute, Vitoria, Spain; University Institute for Regenerative Medicine & Oral Implantology, UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria, Spain
| | - Mar Zalduendo
- BTI-Biotechnology Institute, Vitoria, Spain; University Institute for Regenerative Medicine & Oral Implantology, UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria, Spain
| | - Roberto Tierno
- BTI-Biotechnology Institute, Vitoria, Spain; University Institute for Regenerative Medicine & Oral Implantology, UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria, Spain
| | - Mohammad H Alkhraisat
- BTI-Biotechnology Institute, Vitoria, Spain; University Institute for Regenerative Medicine & Oral Implantology, UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria, Spain
| | - Nerea Osinalde
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
| | - Asier Fullaondo
- University Institute for Regenerative Medicine & Oral Implantology, UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria, Spain; Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain
| | - Ana M Zubiaga
- University Institute for Regenerative Medicine & Oral Implantology, UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria, Spain; Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain
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12
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Wang YS, Chu WH, Zhai JJ, Wang WY, He ZM, Zhao QM, Li CY. High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells. World J Stem Cells 2024; 16:176-190. [PMID: 38455106 PMCID: PMC10915955 DOI: 10.4252/wjsc.v16.i2.176] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 12/15/2023] [Accepted: 01/19/2024] [Indexed: 02/26/2024] Open
Abstract
BACKGROUND Cartilage defects are some of the most common causes of arthritis. Cartilage lesions caused by inflammation, trauma or degenerative disease normally result in osteochondral defects. Previous studies have shown that decellularized extracellular matrix (ECM) derived from autologous, allogenic, or xenogeneic mesenchymal stromal cells (MSCs) can effectively restore osteochondral integrity. AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells (RMCs), a xenogeneic material from antler stem cells, is superior to the currently available treatments for osteochondral defects. METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70% confluence; 50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition. Decellularized sheets of adipocyte-derived MSCs (aMSCs) and antlerogenic periosteal cells (another type of antler stem cells) were used as the controls. Three weeks after ascorbic acid stimulation, the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints. RESULTS The defects were successfully repaired by applying the ECM-sheets. The highest quality of repair was achieved in the RMC-ECM group both in vitro (including cell attachment and proliferation), and in vivo (including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues). Notably, the antler-stem-cell-derived ECM (xenogeneic) performed better than the aMSC-ECM (allogenic), while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells. CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell, particularly the active form (RMC-ECM), can achieve high quality repair/reconstruction of osteochondral defects, suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.
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Affiliation(s)
- Yu-Su Wang
- Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun 130000, Jilin Province, China
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, Jilin Province, China
| | - Wen-Hui Chu
- School of Life Science, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Jing-Jie Zhai
- Department of Oral Implantology, Hospital of Stomatology, Jilin University, Changchun 130000, Jilin Province, China
| | - Wen-Ying Wang
- Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun 130000, Jilin Province, China
| | - Zhong-Mei He
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, Jilin Province, China
| | - Quan-Min Zhao
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, Jilin Province, China
| | - Chun-Yi Li
- Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun 130000, Jilin Province, China.
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13
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Li Y, Deng T, Aili D, Chen Y, Zhu W, Liu Q. Cell Sheet Technology: An Emerging Approach for Tendon and Ligament Tissue Engineering. Ann Biomed Eng 2024; 52:141-152. [PMID: 37731091 DOI: 10.1007/s10439-023-03370-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 09/09/2023] [Indexed: 09/22/2023]
Abstract
Tendon and ligament injuries account for a substantial proportion of disorders in the musculoskeletal system. While non-operative and operative treatment strategies have advanced, the restoration of native tendon and ligament structures after injury is still challenging due to its innate limited regenerative ability. Cell sheet technology is an innovative tool for tissue fabrication and cell transplantation in regenerative medicine. In this review, we first summarize different harvesting procedures and advantages of cell sheet technology, which preserves intact cell-to-cell connections and extracellular matrix. We then describe the recent progress of cell sheet technology from preclinical studies, focusing on the application of stem cell-derived sheets in treating tendon and ligament injuries, as well as highlighting its effects on mitigating inflammation and promoting tendon/graft-bone interface healing. Finally, we discuss several prerequisites for future clinical translation including the selection of appropriate cell source, optimization of preparation process, establishment of suitable animal model, and the fabrication of vascularized complex tissue. We believe this review could potentially provoke new ideas and drive the development of more functional biomimetic tissues using cell sheet technology to meet the needs of clinical patients.
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Affiliation(s)
- Yexin Li
- Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Ting Deng
- Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Dilihumaer Aili
- Department of Orthopedic Surgery, Affiliated Hospital of Traditional Chinese Medicine, Xinjiang Medical University, Ürümqi, People's Republic of China
| | - Yang Chen
- Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Weihong Zhu
- Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Qian Liu
- Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.
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14
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Fawzy El-Sayed KM, Cosgarea R, Sculean A, Doerfer C. Can vitamins improve periodontal wound healing/regeneration? Periodontol 2000 2024; 94:539-602. [PMID: 37592831 DOI: 10.1111/prd.12513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 07/13/2023] [Accepted: 07/19/2023] [Indexed: 08/19/2023]
Abstract
Periodontitis is a complex inflammatory disorder of the tooth supporting structures, associated with microbial dysbiosis, and linked to a number if systemic conditions. Untreated it can result in an irreversible damage to the periodontal structures and eventually teeth loss. Regeneration of the lost periodontium requires an orchestration of a number of biological events on cellular and molecular level. In this context, a set of vitamins have been advocated, relying their beneficial physiological effects, to endorse the biological regenerative events of the periodontium on cellular and molecular levels. The aim of the present article is to elaborate on the question whether or not vitamins improve wound healing/regeneration, summarizing the current evidence from in vitro, animal and clinical studies, thereby shedding light on the knowledge gap in this field and highlighting future research needs. Although the present review demonstrates the current heterogeneity in the available evidence and knowledge gaps, findings suggest that vitamins, especially A, B, E, and CoQ10, as well as vitamin combinations, could exert positive attributes on the periodontal outcomes in adjunct to surgical or nonsurgical periodontal therapy.
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Affiliation(s)
- Karim M Fawzy El-Sayed
- Oral Medicine and Periodontology Department, Faculty of Oral and Dental Medicine, Cairo University, Giza, Egypt
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
| | - Raluca Cosgarea
- Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany
- Department of Periodontology and Peri-implant Diseases, Philips University Marburg, Marburg, Germany
- Clinic for Prosthetic Dentistry, University Iuliu-Hatieganu, Cluj-Napoca, Romania
| | - Anton Sculean
- Department of Periodontology, University of Bern, Bern, Switzerland
| | - Christof Doerfer
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
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15
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Karimi M, Mosaddad SA, Aghili SS, Dortaj H, Hashemi SS, Kiany F. Attachment and proliferation of human gingival fibroblasts seeded on barrier membranes using Wharton's jelly-derived stem cells conditioned medium: An in vitro study. J Biomed Mater Res B Appl Biomater 2024; 112:e35368. [PMID: 38247251 DOI: 10.1002/jbm.b.35368] [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: 07/30/2023] [Revised: 11/12/2023] [Accepted: 12/02/2023] [Indexed: 01/23/2024]
Abstract
The effect of Wharton's jelly mesenchymal stem cells conditioned medium (WJMSCs-CM) and zinc oxide nanoparticles (ZnO-NPs) on cultured human gingival fibroblasts on various barrier membranes was investigated in this study. In this study, human gingival fibroblasts were prepared and cultured on three membranes: collagen membrane, acellular dermal matrix (ADM) with ZnO-NPs, and ADM without ZnO-NPs. WJMSCs-CM was given to the testing groups, while control groups received the same membranes without WJMSCs-CM. Following 48 and 72 h, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests were performed to assess cell survival. Cell proliferation on the membranes was also evaluated using 4',6-diamidino-2-phenylindole (DAPI) staining after 48 and 72 h. Field emission scanning electron microscopy was used to determine membrane surface structure and cell adhesion. Nanoparticles were also subjected to an energy-dispersive x-ray analysis to identify their chemical structure. Two-way analysis of variance was used to conduct the statistical analysis. The p-value ≤.05 was considered significant. When ADM-ZnO-NPs were combined with CM, fibroblast viability, and adhesion significantly differed from ADM-ZnO-NPs alone. DAPI results confirmed cell proliferation in all six groups on both experiment days. The abundance and concentrated distribution of cells during cell proliferation were found in CM-containing membranes, specifically the ADM-ZnO-NPs membrane, demonstrating the improved biocompatibility of the ADM-ZnO-NPs membrane for cell proliferation. The other groups did not significantly differ from one another. WJMSCs-CM positively affected the viability and proliferation of gingival fibroblasts, but only marginally. Under certain conditions, ZnO-NPs below a specific concentration increased the biocompatibility of the membranes.
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Affiliation(s)
- Mohammadreza Karimi
- Student Research Committee, Department of Periodontics, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Ali Mosaddad
- Department of Conservative Dentistry and Bucofacial Prosthesis, Faculty of Odontology, Complutense University of Madrid, Madrid, Spain
| | - Seyedeh Sara Aghili
- Student Research Committee, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hengameh Dortaj
- Department of Tissue Engineering, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyedeh-Sara Hashemi
- Burn and Wound Healing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farin Kiany
- Oral and Dental Disease Research Center, Department of Periodontology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
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16
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Yan S, Lin S, Qiu H, Wang X, He Y, Wang C, Huang Y. Regulation of telomerase towards tumor therapy. Cell Biosci 2023; 13:228. [PMID: 38111043 PMCID: PMC10726632 DOI: 10.1186/s13578-023-01181-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 12/02/2023] [Indexed: 12/20/2023] Open
Abstract
Cancer is an aging-related disease, while aging plays an important role in the development process of tumor, thus the two are inextricably associated. Telomere attrition is one of the recognized hallmark events of senescence. Hence, targeting telomerase which could extends telomere sequences to treat tumors is widely favored. Cancer cells rely on high activity of telomerase to maintain a strong proliferative potential. By inhibiting the expression or protein function of telomerase, the growth of cancer cells can be significantly suppressed. In addition, the human immune system itself has a defense system against malignant tumors. However, excessive cell division results in dramatic shortening on telomeres and decline in the function of immune organs that facilitates cancer cell evasion. It has been shown that increasing telomerase activity or telomere length of these immune cells can attenuate senescence, improve cellular viability, and enhance the immunosuppressive microenvironment of tumor. In this paper, we review the telomerase-targeting progress using different anti-tumor strategies from the perspectives of cancer cells and immune cells, respectively, as well as tracking the preclinical and clinical studies of some representative drugs for the prevention or treatment of tumors.
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Affiliation(s)
- Siyu Yan
- MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China
- Lumiere Therapeutics Co., Ltd., Suzhou, 215000, China
| | - Song Lin
- MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China
| | - Hongxin Qiu
- MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China
| | - Xining Wang
- MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China
| | - Yijun He
- MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China
| | - Chuanle Wang
- MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China
- Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510275, China
| | - Yan Huang
- MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
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Tsatsakis A, Renieri E, Tsoukalas D, Buga AM, Sarandi E, Vakonaki E, Fragkiadaki P, Alegakis A, Nikitovic D, Calina D, Spandidos DA, Docea AO. A novel nutraceutical formulation increases telomere length and activates telomerase activity in middle‑aged rats. Mol Med Rep 2023; 28:232. [PMID: 37921058 PMCID: PMC10668076 DOI: 10.3892/mmr.2023.13119] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 09/19/2023] [Indexed: 11/04/2023] Open
Abstract
Telomeres are major contributors to cell fate and aging through their involvement in cell cycle arrest and senescence. The accelerated attrition of telomeres is associated with aging‑related diseases, and agents able to maintain telomere length (TL) through telomerase activation may serve as potential treatment strategies. The aim of the present study was to assess the potency of a novel telomerase activator on TL and telomerase activity in vivo. The administration of a nutraceutical formulation containing Centella asiatica extract, vitamin C, zinc and vitamin D3 in 18‑month‑old rats for a period of 3 months reduced the telomere shortening rate at the lower supplement dose and increased mean the TL at the higher dose, compared to pre‑treatment levels. TL was determined using the Q‑FISH method in peripheral blood mononuclear cells collected from the tail vein of the rats and cultured with RPMI‑1640 medium. In both cases, TLs were significantly longer compared to the untreated controls (P≤0.001). In addition, telomerase activity was increased in the peripheral blood mononuclear cells of both treatment groups. On the whole, the present study demonstrates that the nutraceutical formulation can maintain or even increase TL and telomerase activity in middle‑aged rats, indicating a potential role of this formula in the prevention and treatment of aging‑related diseases.
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Affiliation(s)
- Aristidis Tsatsakis
- Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003 Heraklion, Greece
- Lifeplus S.A., 71003 Heraklion, Greece
| | - Elisavet Renieri
- Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003 Heraklion, Greece
- Lifeplus S.A., 71003 Heraklion, Greece
| | - Dimitris Tsoukalas
- Metabolomic Medicine, Health Clinic for Autoimmune and Chronic Diseases, 10674 Athens, Greece
- European Institute of Molecular Medicine (EINUMM), I-00198 Rome, Italy
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Ana Maria Buga
- Department of Biochemistry, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Evangelia Sarandi
- Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003 Heraklion, Greece
- Metabolomic Medicine, Health Clinic for Autoimmune and Chronic Diseases, 10674 Athens, Greece
| | - Elena Vakonaki
- Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003 Heraklion, Greece
- Lifeplus S.A., 71003 Heraklion, Greece
| | - Persefoni Fragkiadaki
- Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003 Heraklion, Greece
- Lifeplus S.A., 71003 Heraklion, Greece
| | - Athanasios Alegakis
- Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003 Heraklion, Greece
- Lifeplus S.A., 71003 Heraklion, Greece
| | - Dragana Nikitovic
- Laboratory of Histology-Embryology, Medical School, University of Crete, 71003 Heraklion, Greece
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Demetrios A. Spandidos
- Laboratory of Clinical Virology, Medical School, University of Crete, 71003 Heraklion, Greece
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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18
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Wang Y, Wu M, Xiang L, Liu S, Luo G, Lin Q, Xiao L. Association of Dietary Vitamin C Consumption with Serum Klotho Concentrations. Foods 2023; 12:4230. [PMID: 38231677 DOI: 10.3390/foods12234230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 11/03/2023] [Accepted: 11/21/2023] [Indexed: 01/19/2024] Open
Abstract
BACKGROUND Klotho is widely recognized as a protein that combats aging and possesses antioxidative characteristics, which have been implicated in the pathophysiology of numerous diseases. There is emerging evidence suggesting that the consumption of dietary nutrients, particularly those rich in antioxidants, could be associated with serum Klotho concentrations. Dietary vitamin C is one of the critical nutrients that possesses antioxidant properties. Nonetheless, the association between dietary vitamin C consumption and serum Klotho concentrations remains unclear. OBJECTIVE Aiming to evaluate the relationship between serum Klotho concentrations and dietary vitamin C consumption among Americans aged 40 to 79, we conducted a population-based study. METHODS From the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016, a grand total of 11,282 individuals who met the criteria were selected as eligible participants for the study. Serum Klotho concentrations were measured using an ELISA kit that is commercially available. Trained interviewers evaluated the consumption of dietary vitamin C in the diet through a 24-hour dietary recall technique. A generalized linear model was used to evaluate the correlation between the consumption of dietary vitamin C in the diet and serum Klotho concentrations. Further examination was conducted using restricted cubic spline (RCS) analysis to explore the non-linear correlation between dietary vitamin C consumption in the diet and serum Klotho concentrations. RESULTS After accounting for possible confounding factors, serum Klotho concentrations rose by 1.17% (95% confidence interval (CI): 0.37%, 1.99%) with every standard deviation (SD) rise in dietary vitamin C consumption. With the first quintile of dietary vitamin C consumption as a reference, the percentage change of serum Klotho concentrations in the fifth quintile of dietary vitamin C consumption was 3.66% higher (95% CI: 1.05%, 6.32%). In older, normal-weight, and male participants, the subgroup analysis revealed a stronger correlation between dietary vitamin C consumption and serum Klotho concentrations. Analysis of RCS showed a linear positive association between dietary vitamin C consumption and the levels of serum Klotho concentrations. CONCLUSION The findings of this research indicate a strong and positive correlation between dietary vitamin C consumption and serum Klotho concentrations among the general adult population in the United States. Further studies are needed to validate the present findings and to explore specific mechanisms.
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Affiliation(s)
- Yan Wang
- Xiangya School of Public Health, Central South University, Changsha 410078, China
| | - Mingyang Wu
- Xiangya School of Public Health, Central South University, Changsha 410078, China
| | - Lu Xiang
- Xiangya School of Public Health, Central South University, Changsha 410078, China
| | - Si Liu
- Xiangya School of Public Health, Central South University, Changsha 410078, China
| | - Gang Luo
- Xiangya School of Public Health, Central South University, Changsha 410078, China
| | - Qian Lin
- Xiangya School of Public Health, Central South University, Changsha 410078, China
| | - Lin Xiao
- Xiangya School of Public Health, Central South University, Changsha 410078, China
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19
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Yang Z, Ma L, Du C, Wang J, Zhang C, Hu L, Wang S. Dental pulp stem cells accelerate wound healing through CCL2-induced M2 macrophages polarization. iScience 2023; 26:108043. [PMID: 37829207 PMCID: PMC10565783 DOI: 10.1016/j.isci.2023.108043] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 09/18/2023] [Accepted: 09/21/2023] [Indexed: 10/14/2023] Open
Abstract
The crosstalk between mesenchymal stem cells (MSCs) and the host immune function plays a key role in the efficiency of tissue regeneration and wound healing. However, the difference in immunological modulation and tissue regeneration function between MSCs from different sources remains unclear. Compared to PDLSCs, BMMSCs, and ADSCs, DPSCs exhibited greater tissue regeneration potential and triggered more M2 macrophages in vivo. DPSCs elicited the polarization of M2a macrophages by conditioned medium and transwell assay and exhibited higher expression levels of C-C motif chemokine ligand 2 (CCL2). Specific blocking of CCL2 could significantly inhibit the DPSCs-induced polarization of M2 macrophages. DPSCs promoted wound healing of the palatal mucosa and M2 macrophages polarization in vivo, which could be significantly impaired by CCL2-neutralized antibody. Our data indicate that DPSCs exert better tissue regeneration potential and immunoregulatory function by secreting CCL2, which can enhance MSCs-mediated tissue regeneration or wound healing.
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Affiliation(s)
- Zi Yang
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, China
| | - Linsha Ma
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Conglin Du
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jingsong Wang
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medicine, Beijing, China
| | - Chunmei Zhang
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Lei Hu
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Department of Prosthodontics, Beijing Stomatological Hospital, Capital Medical University, Beijing, China
| | - Songlin Wang
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medicine, Beijing, China
- Laboratory for Oral and General Health Integration and Translation, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Research Units of Tooth Development and Regeneration, Chinese Academy of Medical Sciences, Beijing, China
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20
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Huang D, Liang J, Yang J, Yang C, Wang X, Dai T, Steinberg T, Li C, Wang F. Current Status of Tissue Regenerative Engineering for the Treatment of Uterine Infertility. TISSUE ENGINEERING. PART B, REVIEWS 2023; 29:558-573. [PMID: 37335062 DOI: 10.1089/ten.teb.2022.0226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/21/2023]
Abstract
With the recent developments in tissue engineering, scientists have attempted to establish seed cells from different sources, create cell sheets through various technologies, implant them on scaffolds with various spatial structures, or load scaffolds with cytokines. These research results are very optimistic, bringing hope to the treatment of patients with uterine infertility. In this article, we reviewed articles related to the treatment of uterine infertility from the aspects of experimental treatment strategy, seed cells, scaffold application, and repair criteria so as to provide a basis for future research.
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Affiliation(s)
- Di Huang
- Shandong First Medical University, Jinan, China
| | - Junhui Liang
- Departments of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Jie Yang
- The Affiliated Taian City Central Hospital of Qingdao University, Taian, China
| | - Chunrun Yang
- Departments of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xin Wang
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Ultrasonography, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Tianyu Dai
- Shandong First Medical University, Jinan, China
| | - Thorsten Steinberg
- Division of Oral Biotechnology, Center for Dental Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Changzhong Li
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Fei Wang
- Departments of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
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21
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Ratre P, Chauhan P, Bhargava A, Tiwari R, Thareja S, Srivastava RK, Mishra PK. Nano-engineered vitamins as a potential epigenetic modifier against environmental air pollutants. REVIEWS ON ENVIRONMENTAL HEALTH 2023; 38:547-564. [PMID: 35724323 DOI: 10.1515/reveh-2022-0027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 05/23/2022] [Indexed: 06/15/2023]
Abstract
Air pollution has emerged as a serious threat to human health due to close association with spectrum of chronic ailments including cardiovascular disorders, respiratory diseases, nervous system dysfunctions, diabetes and cancer. Exposure to air-borne pollutants along with poor eating behaviours and inferior dietary quality irreversibly impacts epigenomic landscape, leading to aberrant transcriptional control of gene expression which is central to patho-physiology of non-communicable diseases. It is assumed that nutriepigenomic interventions such as vitamins can control such adverse effects through their immediate action on mitochondrial epigenomic-axis. Importantly, the exhaustive clinical utility of vitamins-interceded epigenetic synchronization is not well characterized. Therefore, improving the current limitations linked to stability and bioavailability issues in vitamin formulations is highly warranted. The present review not only sums up the available data on the role of vitamins as potential epigenetic modifiers but also discusses the importance of nano-engineered vitamins as potential epidrugs for dietary and pharmacological intervention to mitigate the long-term effects of air pollution toxicity.
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Affiliation(s)
- Pooja Ratre
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Prachi Chauhan
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Arpit Bhargava
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Rajnarayan Tiwari
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Suresh Thareja
- Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, India
| | | | - Pradyumna Kumar Mishra
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
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22
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Wahyuningsih KA, Pangkahila WI, Weta IWW, Widiana IGR, Wahyuniari IAI. Potential Utilisation of Secretome from Ascorbic Acid-Supplemented Stem Cells in Combating Skin Aging: Systematic Review of A Novel Idea. CELL JOURNAL 2023; 25:591-602. [PMID: 37718762 PMCID: PMC10520989 DOI: 10.22074/cellj.2023.1995999.1253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 06/10/2023] [Accepted: 06/24/2023] [Indexed: 09/19/2023]
Abstract
The secretome of stem cells consists of a spectrum of bioactive factors secreted by stem cells grown in culture mediacytokines, chemokines, and growth factors in addition to extracellular vesicles (exosomes and microvesicles). Ease of handling and storage of secretomes along with their bioactivity towards processes in skin aging and customizability makes them an appealing prospective therapy for skin aging. This systematic review aims to investigate the potential usage of ascorbic acid (AA)-supplemented stem cell secretomes (SCS) in managing skin aging. We extracted articles from three databases: PubMed, Scopus, and Cochrane. This review includes in vitro, in vivo, and clinical studies published in English that discuss the correlation of AA-supplemented-SCS with skin aging. We identified 1111 articles from database and non-database sources from which nine studies met the inclusion criteria. However, the study results were less specific due to the limited amount of available research that specifically assessed the effects of AAsupplemented SCS in skin aging. Although further studies are necessary, the AA modification of SCS is a promising potential for improving skin health.
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Affiliation(s)
- Komang Ardi Wahyuningsih
- Doctoral Program, Faculty of Medicine, Universitas Udayana, Denpasar, Indonesia.
- Histology Department, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia
| | - Wimpie I Pangkahila
- Doctoral Program, Faculty of Medicine, Universitas Udayana, Denpasar, Indonesia
| | - I Wayan Weta Weta
- Doctoral Program, Faculty of Medicine, Universitas Udayana, Denpasar, Indonesia
| | - I Gde Raka Widiana
- Doctoral Program, Faculty of Medicine, Universitas Udayana, Denpasar, Indonesia
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23
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Lenz LS, Wink MR. The other side of the coin: mesenchymal stromal cell immortalization beyond evasion of senescence. Hum Cell 2023; 36:1593-1603. [PMID: 37341871 DOI: 10.1007/s13577-023-00925-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 05/23/2023] [Indexed: 06/22/2023]
Abstract
Mesenchymal stromal cells (MSC) are promising options to cellular therapy to several clinical disorders, mainly because of its ability to immunomodulate and differentiate into different cell types. Even though MSC can be isolated from different sources, a major challenge to understanding the biological effects is that the primary cells undergo replicative senescence after a limited number of cell divisions in culture, requiring time-consuming and technically challenging approaches to get a sufficient cell number for clinical applications. Therefore, a new isolation, characterization, and expansion is necessary every time, which increases the variability and is time-consuming. Immortalization is a strategy that can overcome these challenges. Therefore, here, we review the different methodologies available to cellular immortalization, and discuss the literature regarding MSC immortalization and the broader biological consequences that extend beyond the mere increase in proliferation potential.
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Affiliation(s)
- Luana Suéling Lenz
- Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, 90050-170, Brazil
| | - Márcia Rosângela Wink
- Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, 90050-170, Brazil.
- Departamento de Ciências Básicas da Saúde (DCBS), Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, 90050-170, Brazil.
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24
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Sui BD, Zheng CX, Zhao WM, Xuan K, Li B, Jin Y. Mesenchymal condensation in tooth development and regeneration: a focus on translational aspects of organogenesis. Physiol Rev 2023; 103:1899-1964. [PMID: 36656056 DOI: 10.1152/physrev.00019.2022] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 12/26/2022] [Accepted: 01/16/2023] [Indexed: 01/20/2023] Open
Abstract
The teeth are vertebrate-specific, highly specialized organs performing fundamental functions of mastication and speech, the maintenance of which is crucial for orofacial homeostasis and is further linked to systemic health and human psychosocial well-being. However, with limited ability for self-repair, the teeth can often be impaired by traumatic, inflammatory, and progressive insults, leading to high prevalence of tooth loss and defects worldwide. Regenerative medicine holds the promise to achieve physiological restoration of lost or damaged organs, and in particular an evolving framework of developmental engineering has pioneered functional tooth regeneration by harnessing the odontogenic program. As a key event of tooth morphogenesis, mesenchymal condensation dictates dental tissue formation and patterning through cellular self-organization and signaling interaction with the epithelium, which provides a representative to decipher organogenetic mechanisms and can be leveraged for regenerative purposes. In this review, we summarize how mesenchymal condensation spatiotemporally assembles from dental stem cells (DSCs) and sequentially mediates tooth development. We highlight condensation-mimetic engineering efforts and mechanisms based on ex vivo aggregation of DSCs, which have achieved functionally robust and physiologically relevant tooth regeneration after implantation in animals and in humans. The discussion of this aspect will add to the knowledge of development-inspired tissue engineering strategies and will offer benefits to propel clinical organ regeneration.
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Affiliation(s)
- Bing-Dong Sui
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Chen-Xi Zheng
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Wan-Min Zhao
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Kun Xuan
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
- Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Bei Li
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Yan Jin
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
- Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, Shaanxi, China
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25
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Hu D, Li X, Li J, Tong P, Li Z, Lin G, Sun Y, Wang J. The preclinical and clinical progress of cell sheet engineering in regenerative medicine. Stem Cell Res Ther 2023; 14:112. [PMID: 37106373 PMCID: PMC10136407 DOI: 10.1186/s13287-023-03340-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 04/13/2023] [Indexed: 04/29/2023] Open
Abstract
Cell therapy is an accessible method for curing damaged organs or tissues. Yet, this approach is limited by the delivery efficiency of cell suspension injection. Over recent years, biological scaffolds have emerged as carriers of delivering therapeutic cells to the target sites. Although they can be regarded as revolutionary research output and promote the development of tissue engineering, the defect of biological scaffolds in repairing cell-dense tissues is apparent. Cell sheet engineering (CSE) is a novel technique that supports enzyme-free cell detachment in the shape of a sheet-like structure. Compared with the traditional method of enzymatic digestion, products harvested by this technique retain extracellular matrix (ECM) secreted by cells as well as cell-matrix and intercellular junctions established during in vitro culture. Herein, we discussed the current status and recent progress of CSE in basic research and clinical application by reviewing relevant articles that have been published, hoping to provide a reference for the development of CSE in the field of stem cells and regenerative medicine.
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Affiliation(s)
- Danping Hu
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, China
- HANGZHOU CHEXMED TECHNOLOGY CO., LTD, Hangzhou, 310000, China
| | - Xinyu Li
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, China
| | - Jie Li
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, China
| | - Pei Tong
- Hospital of Hunan Guangxiu, Medical College of Hunan Normal University, Hunan Normal University, Changsha, 410008, China
| | - Zhe Li
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, China
| | - Ge Lin
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, China
- National Engineering and Research Center of Human Stem Cells, Changsha, 410008, China
- Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, Changsha, 410008, China
| | - Yi Sun
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, China.
- National Engineering and Research Center of Human Stem Cells, Changsha, 410008, China.
- Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, Changsha, 410008, China.
| | - Juan Wang
- Shanghai Biomass Pharmaceutical Product Evaluation Professional Public Service Platform, Center for Pharmacological Evaluation and Research, China State Institute of Pharmaceutical Industry, Shanghai, 200437, China.
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26
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Moghaddam SV, Abedi F, Lotfi H, Salehi R, Barzegar A, Eslaminejad MB, Khalili M, Alizadeh E. An efficient method for cell sheet bioengineering from rBMSCs on thermo-responsive PCL-PEG-PCL copolymer. J Biol Eng 2023; 17:27. [PMID: 37024910 PMCID: PMC10080813 DOI: 10.1186/s13036-023-00346-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 03/25/2023] [Indexed: 04/08/2023] Open
Abstract
Utilizing both medium enrichment and a thermos-responsive substrate to maintain the cell-to-cell junctions and extracellular matrix (ECM) intact, cell sheet technology has emerged as a ground-breaking approach. Investigating the possibility of using sodium selenite (as medium supplementation) and PCL-PEG-PCL (as vessel coating substrate) in the formation of the sheets from rat bone marrow-derived mesenchymal stem cells (rBMSCs) was the main goal of the present study. To this end, first, Polycaprolactone-co-Poly (ethylene glycol)-co-Polycaprolactone triblock copolymer (PCEC) was prepared by ring-opening copolymerization method and characterized by FTIR, 1 H NMR, and GPC. The sol-gel-sol phase transition temperature of the PCEC aqueous solutions with various concentrations was either measured. Next, rBMSCs were cultured on the PCEC, and let be expanded in five different media containing vitamin C (50 µg/ml), sodium selenite (0.1 µM), vitamin C and sodium selenite (50 µg/ml + 0.1 µM), Trolox, and routine medium. The proliferation of the cells exposed to each material was evaluated. Produced cell sheets were harvested from the polymer surface by temperature reduction and phenotypically analyzed via an inverted microscope, hematoxylin and eosin (H&E) staining, and field emission scanning electron microscopy (FESEM). Through the molecular level, the expression of the stemness-related genes (Sox2, Oct-4, Nanog), selenium-dependent enzymes (TRX, GPX-1), and aging regulator gene (Sirt1) were measured by q RT-PCR. Senescence in cell sheets was checked by beta-galactosidase assay. The results declared the improved ability of the rBMSCs for osteogenesis and adipogenesis in the presence of antioxidants vitamin C, sodium selenite, and Trolox in growth media. The data indicated that in the presence of vitamin C and sodium selenite, the quality of the cell sheet was risen by reducing the number of senescent cells and high transcription of the stemness genes. Monolayers produced by sodium selenite was in higher-quality than the ones produced by vitamin C.
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Affiliation(s)
- Sevil Vaghefi Moghaddam
- Clinical Research Development, Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Abedi
- Clinical Research Development, Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hajie Lotfi
- Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Roya Salehi
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Abolfazl Barzegar
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
| | - Mohamadreza Baghaban Eslaminejad
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Mostafa Khalili
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Effat Alizadeh
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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27
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Cai Y, Zhong YD, Zhang H, Lu PL, Liang YY, Hu B, Wu H. Association between dietary vitamin C and telomere length: A cross-sectional study. Front Nutr 2023; 10:1025936. [PMID: 36776610 PMCID: PMC9908946 DOI: 10.3389/fnut.2023.1025936] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 01/04/2023] [Indexed: 01/28/2023] Open
Abstract
Background Currently, telomere length is known to reflect the replication potential and longevity of cells, and many studies have reported that telomere length is associated with age-related diseases and biological aging. Studies have also shown that vitamin C acts as an oxidant and free radical scavenger to protect cells from oxidative stress and telomere wear, thus achieving anti-aging effects. At present, there are few and incomplete studies on the relationship between vitamin C and telomere length, so this study aims to explore the relationship between vitamin C and telomere length. Methods This study used cross-sectional data from the National Health and Nutrition Examination Surveys (NHANES) database from 1999 to 2002, a total of 7,094 participants were selected from all races in the United States. Male participants accounted for 48.2% and female participants accounted for 51.8%. The correlation between vitamin C and telomere length was assessed using a multiple linear regression model, and the effect of dietary vitamin C on telomere length was obtained after adjusting for confounding factors such as age, gender, race, body mass index (BMI), and poverty income ratio (PIR). Results This cross-sectional study showed that vitamin C was positively correlated with telomere length, with greater dietary vitamin C intake associated with longer telomeres (β = 0.03, 95% CI: 0.01-0.05, P = 0.003). Conclusion This study shows that vitamin C intake is positively correlated with human telomere length, which is of guiding significance for our clinical guidance on people's health care, but our study need to be confirmed by more in-depth and comprehensive other research results.
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Affiliation(s)
- Yuan Cai
- Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China,Guangzhou Medical University, Guangzhou, China
| | - Yu-di Zhong
- Guangdong Ocean University, Zhanjiang, China
| | - Hao Zhang
- Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China,Department of Medical Imaging, The Second Clinical School of Guangzhou Medical University, Guangzhou, China
| | - Pei-lin Lu
- Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China,Department of Clinical Medicine, Guangzhou Medical University, Guangzhou, China
| | - Yong-yi Liang
- Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China,Guangzhou Medical University, Guangzhou, China
| | - Biao Hu
- Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China,Guangzhou Medical University, Guangzhou, China,Department of Clinical Medicine, Guangzhou Medical University, Guangzhou, China,*Correspondence: Biao Hu,
| | - Hui Wu
- Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China,Hui Wu,
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28
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Chaudhary DS, Parwani SR, Barkhade S, Gajbhiye M, Parwani R, Sikka G, Kawadkar K, Soni NJ, Armogida NG, Dadlani H, Spagnuolo G. Physiological Gingival Melanin Hyperpigmentation Treatment with Injectable Vitamin C and Scalpel Technique: A Randomised Controlled Clinical Trial. Int J Dent 2023; 2023:4586923. [PMID: 37252615 PMCID: PMC10212675 DOI: 10.1155/2023/4586923] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 01/03/2023] [Accepted: 01/04/2023] [Indexed: 10/29/2023] Open
Abstract
Harmony between facial complexion and gingival health goes hand in hand. Gingival depigmentation is an aesthetic correction of hyperactive melanocytes in gingival tissues that lead to hyperpigmentation. Current study compares depigmentation, pain scores, and itching with scalpel technique and nonsurgical intramucosal Vitamin C injection. 30 individuals in the age range of 18-40 years conscious of dark gums were randomly allocated to test and control group by lottery method. Thorough Phase I therapy was performed one week before the procedure. Area and intensity of depigmentation were evaluated preoperatively and postoperatively; pain score, itching, and repigmentation percentage were the postoperative parameters. After 24 hrs, test group showed significantly lesser VAS score for pain as compared to control group. There was no statistically significant difference in preoperative area of pigmentation between the test and control group (p=0.936). Postoperatively also, there was no statistically significant difference in area of pigmentation between the test and control group (p=0.932). For comparing area of pigmentation, an independent t-test was applied and Mann-Whitney test was used for differentiating the intensity of pigmentation, repigmentation, and VAS score between the groups. The study concluded that Vitamin C mesotherapy and scalpel technique showed comparable results in reduction of areas and intensity of gingival hyperpigmentation.
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Affiliation(s)
- Dhanashree S. Chaudhary
- Department of Periodontology, V.Y.W.S. Dental College and Hospital, Amravati, Maharashtra 444602, India
| | - Simran R. Parwani
- Department of Periodontology, V.Y.W.S. Dental College and Hospital, Amravati, Maharashtra 444602, India
| | - Shital Barkhade
- Department of Periodontology, V.Y.W.S. Dental College and Hospital, Amravati, Maharashtra 444602, India
| | - Minal Gajbhiye
- Department of Periodontology, V.Y.W.S. Dental College and Hospital, Amravati, Maharashtra 444602, India
| | - Rajkumar Parwani
- Department of Oral Pathology, V.Y.W.S. Dental College and Hospital, Amravati, Maharashtra 444602, India
| | - Geetanjali Sikka
- Department of Periodontology, Eklavya Dental College & Hospital Kotpulti, Rajasthan 303108, India
| | - Kshipra Kawadkar
- Department of Periodontology, V.Y.W.S. Dental College and Hospital, Amravati, Maharashtra 444602, India
| | - Nishita Jaju Soni
- Department of Periodontology, V.Y.W.S. Dental College and Hospital, Amravati, Maharashtra 444602, India
| | - Niccolò Giuseppe Armogida
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples 80131, Italy
| | - Himanshu Dadlani
- Department of Periodontology, Kalka Dental College, Meerut 250002, India
- Kalka Dental College, Meerut 250016, India
| | - Gianrico Spagnuolo
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples 80131, Italy
- Therapeutic Dentistry Department, Institute for Dentistry, Sechenov University, Moscow 119991, Russia
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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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Guan S, Wu S, Li G, Xiao J, Gao B. Macromolecular crowding facilitates rapid fabrication of intact, robust cell sheets. Biotechnol Lett 2023; 45:57-67. [PMID: 36550337 DOI: 10.1007/s10529-022-03336-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 11/13/2022] [Accepted: 11/28/2022] [Indexed: 12/24/2022]
Abstract
OBJECTIVES To develop a rapid and simple method to fabricate intact, robust cell sheets from common cell culture dishes by combination of a macromolecular crowding (MMC) reagent and vitamin C. RESULTS It was found that 3T3 fibroblasts or human bone marrow mesenchymal stem cells (hBMSCs) and their secreted cell derived extracellular matrices could be easily detached as intact cell sheets under gently pipetting after treated by MMC and vitamin C for 4 days. This method also allowed fabrication of functional multi-layered hepatic cell sheets by culturing 10 × 104 cells/cm2 HepG2 cells on top of confluent 3T3 fibroblast layers. What's more, MMC induced hBMSC cell sheets demonstrated 1.9 times larger area and 1.6 times greater cell number than that of cell sheets harvested from temperature-responsive cell culture dishes. CONCLUSION MMC based method make it possible to fabricate various types of cell sheets more conveniently, economically, and thus may facilitate wide application of cell sheet technology.
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Affiliation(s)
- Shuwen Guan
- National Engineering Research Center for Healthcare Devices, Guangdong Key Lab of Medical Electronic Instruments and Polymer Materials Products, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, No. 1307, Middle Section of Guangzhou Avenue, Tianhe District, Guangzhou, 510550, Guangdong, China
| | - Shipeng Wu
- Department of Stomatology, Shanghai Eighth People's Hospital, Shanghai, China
| | - Gang Li
- Department of Dental Implantation, Guangdong Delun Medical Group, Guangzhou, China
| | - Jiangwei Xiao
- National Engineering Research Center for Healthcare Devices, Guangdong Key Lab of Medical Electronic Instruments and Polymer Materials Products, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, No. 1307, Middle Section of Guangzhou Avenue, Tianhe District, Guangzhou, 510550, Guangdong, China
| | - Botao Gao
- National Engineering Research Center for Healthcare Devices, Guangdong Key Lab of Medical Electronic Instruments and Polymer Materials Products, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, No. 1307, Middle Section of Guangzhou Avenue, Tianhe District, Guangzhou, 510550, Guangdong, China.
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Guo T, Yuan X, Li X, Liu Y, Zhou J. Bone regeneration of mouse critical-sized calvarial defects with human mesenchymal stem cell sheets co-expressing BMP2 and VEGF. J Dent Sci 2023; 18:135-144. [PMID: 36643246 PMCID: PMC9831827 DOI: 10.1016/j.jds.2022.06.020] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 06/20/2022] [Indexed: 01/18/2023] Open
Abstract
Background/purpose Over-dependence on existing synthetic scaffolds and insufficient osteoinductive and vasculogenic growth factors have limited the development of bone regeneration. The study aimed to assess the feasibility of using marrow-derived mesenchymal stem cells (BMSCs) cell sheets co-expressing bone morphogenetic proteins 2 (BMP2) and vascular endothelial growth factor (VEGF) for repairing critical-sized calvarial defects. Materials and methods BMSCs cell sheets were genetically engineered to express BMP2/VEGF alone or together. Alterations in osteogenic markers were examined by quantitative real-time PCR (qRT-PCR) and western blotting. A critical-sized calvarial bone defect model was used to investigate the osteogenesis effects of BMP2/VEGF cell sheets alone or in combination. The efficacy was assessed with micro-computed tomography (micro-CT) and histology. Results In vitro, the expression of BMP2 and VEGF through lentiviral transduction was confirmed by qRT-PCR and western blotting against BMP2 and VEGF. Lentiviral delivery of BMP2 and VEGF resulted in the upregulation of osteogenic markers. In vivo, in a critical-sized calvarial bone defect model, 3D-reconstructed micro-CT images revealed that treatment of the calvarial defects with the BMP2/VEGF cell sheet resulted in significantly greater amounts of newly formed bone at 8 weeks after surgery than treatment with cell sheets with single gene transduction or vehicle controls. The results were confirmed by histological assessment by H&E staining and Masson staining. Conclusion This study demonstrates that BMP2/VEGF co-expressing BMSCs sheets promote bone regeneration in critical-sized calvarial bone defects. The BMP2/VEGF cell sheets provide a functional bioactive scaffold for critical-size bone reconstruction.
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Affiliation(s)
- Tingting Guo
- Department of General Dentistry and Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing, PR China
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, PR China
| | - Xiaohong Yuan
- Department of Pathology, Beijing Stomatological Hospital, Capital Medical University, Beijing, PR China
| | - Xin Li
- Department of Preventive Dentistry, Beijing Stomatological Hospital, Capital Medical University, Beijing, PR China
| | - Yi Liu
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, PR China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China
| | - Jian Zhou
- Department of VIP Dental Service, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, PR China
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Radmand F, Baseri M, Farsadbakhsh M, Azimi A, Dizaj SM, Sharifi S. A Novel Perspective on Tissue Engineering Potentials of Periodontal Ligament Stem Cells. Open Dent J 2022. [DOI: 10.2174/18742106-v16-e221006-2021-216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
It is challenging to completely and predictably regenerate the missing periodontal tissues caused by the trauma or disease. To regenerate the periodontium, there is a need to consider several aspects that co-occur with periodontal development. This study provides an overview of the most up-to-date investigations on the characteristics and immunomodulatory features of Periodontal Ligament Stem Cells (PDLSCs) and the recent interventions performed using these cells, focusing on cell survival, proliferation, and differentiation. Keeping in mind the relationship between age and potency of PDLSCs, this work also demonstrates the necessity of establishing dental-derived stem cell banks for tissue regeneration applications. The data were collected from Pubmed and Google Scholar databases with the keywords of periodontal ligament stem cells, tissue engineering, characteristics, and stem cell therapy. The results showed the presence of wide-ranging research reports supporting the usability of PDLSCs for periodontal reconstruction. However, a better understanding of self-restoration for adequate regulation of adult stem cell growth is needed for various applied purposes.
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Zhao Z, Liu J, Weir MD, Schneider A, Ma T, Oates TW, Xu HHK, Zhang K, Bai Y. Periodontal ligament stem cell-based bioactive constructs for bone tissue engineering. Front Bioeng Biotechnol 2022; 10:1071472. [PMID: 36532583 PMCID: PMC9755356 DOI: 10.3389/fbioe.2022.1071472] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 11/17/2022] [Indexed: 09/29/2023] Open
Abstract
Objectives: Stem cell-based tissue engineering approaches are promising for bone repair and regeneration. Periodontal ligament stem cells (PDLSCs) are a promising cell source for tissue engineering, especially for maxillofacial bone and periodontal regeneration. Many studies have shown potent results via PDLSCs in bone regeneration. In this review, we describe recent cutting-edge researches on PDLSC-based bone regeneration and periodontal tissue regeneration. Data and sources: An extensive search of the literature for papers related to PDLSCs-based bioactive constructs for bone tissue engineering was made on the databases of PubMed, Medline and Google Scholar. The papers were selected by three independent calibrated reviewers. Results: Multiple types of materials and scaffolds have been combined with PDLSCs, involving xeno genic bone graft, calcium phosphate materials and polymers. These PDLSC-based constructs exhibit the potential for bone and periodontal tissue regeneration. In addition, various osteo inductive agents and strategies have been applied with PDLSCs, including drugs, biologics, gene therapy, physical stimulation, scaffold modification, cell sheets and co-culture. Conclusoin: This review article demonstrates the great potential of PDLSCs-based bioactive constructs as a promising approach for bone and periodontal tissue regeneration.
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Affiliation(s)
- Zeqing Zhao
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
| | - Jin Liu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, China
| | - Michael D. Weir
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
| | - Abraham Schneider
- Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States
| | - Tao Ma
- Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States
| | - Thomas W. Oates
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
| | - Hockin H. K. Xu
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
- Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, United States
- Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Ke Zhang
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
| | - Yuxing Bai
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
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Liu L, Li X, Bu W, Jin N, Meng Y, Wang Y, Wang D, Xu X, Zhou D, Sun H. Carbon dots enhance extracellular matrix secretion for dentin-pulp complex regeneration through PI3K/Akt/mTOR pathway-mediated activation of autophagy. Mater Today Bio 2022; 16:100344. [PMID: 35833197 PMCID: PMC9272035 DOI: 10.1016/j.mtbio.2022.100344] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/24/2022] [Accepted: 06/25/2022] [Indexed: 12/11/2022] Open
Abstract
Pulp injury is one of the most common clinical diseases, and severe cases are usually associated with the functional loss of the tooth, while the current clinical treatment modality is only a cavity filling procedure without the regeneration of the dentin-pulp complex, thus leading to a devitalized and brittle tooth. In this study, carbon dots (CDots) with excellent biocompatibility are prepared from ascorbic acid and polyethyleneimine via a hydrothermal method. The as-prepared CDots can enhance extracellular matrix (ECM) secretion of human dental pulp stem cells (DPSCs), giving rise to increased cell adhesion on ECM and a stronger osteogenic/odontogenic differentiation capacity of DPSCs. Further, the mechanism underlying CDots-enhanced ECM secretion is revealed by the transcriptome analysis, Western blot assay and molecular dynamics simulation, identifying that the pharmacological activities of CDots are originated from a reasonable activation of the autophagy, which is mediated by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Based on the abundant CDots-induced ECM and thereby the reinforcement of the cell-ECM adhesion, an intact dental pulp stem cell sheet can be achieved, which in return promote in vivo the efficient regeneration of dentin-pulp complex as well as blood vessels.
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Affiliation(s)
- Lili Liu
- Hospital of Stomatology, Jilin University, Changchun, 130021, PR China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Jilin University, Changchun, 130021, PR China
| | - Xianjing Li
- Hospital of Stomatology, Jilin University, Changchun, 130021, PR China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Jilin University, Changchun, 130021, PR China
| | - Wenhuan Bu
- School and Hospital of Stomatology, China Medical University, Shenyang, 110122, PR China
| | - Nianqiang Jin
- School and Hospital of Stomatology, China Medical University, Shenyang, 110122, PR China
| | - Yuan Meng
- School and Hospital of Stomatology, China Medical University, Shenyang, 110122, PR China
| | - Yi Wang
- Graduate Program in Applied Physics, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA
| | - Duan Wang
- Hospital of Stomatology, Jilin University, Changchun, 130021, PR China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Jilin University, Changchun, 130021, PR China
| | - Xiaowei Xu
- Hospital of Stomatology, Jilin University, Changchun, 130021, PR China
| | - Ding Zhou
- Hospital of Stomatology, Jilin University, Changchun, 130021, PR China
| | - Hongchen Sun
- Hospital of Stomatology, Jilin University, Changchun, 130021, PR China
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Yan J, Zhang L, Li L, He W, Liu W. Developmentally engineered bio-assemblies releasing neurotrophic exosomes guide in situ neuroplasticity following spinal cord injury. Mater Today Bio 2022; 16:100406. [PMID: 36065352 PMCID: PMC9440432 DOI: 10.1016/j.mtbio.2022.100406] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 08/12/2022] [Accepted: 08/18/2022] [Indexed: 11/17/2022]
Abstract
The emerging tissue-engineered bio-assemblies are revolutionizing the regenerative medicine, and provide a potential program to guarantee predictive performance of stem-cell-derived treatments in vivo and hence support their clinical translation. Mesenchymal stem cell (MSC) showed the attractive potential for the therapy of nervous system injuries, especially spinal cord injury (SCI), and yet failed to make an impact on clinical outcomes. Herein, under the guidance of the embryonic development theory that appropriate cellular coarctations or clustering are pivotal initiators for the formation of geometric and functional tissue structures, a developmentally engineered strategy was established to assemble DPMSCs into a bio-assembly termed Spinor through a three-level sequential induction programme including reductant, energy and mechanical force stimulation. Spinor exhibited similar geometric construction with spinal cord tissue and attain autonomy to released exosome with the optimized quantity and quality for suppressing cicatrization and inflammation and promoting axonal regeneration. As a spinal cord fascia and exosome mothership, Spinor guided the in-situ neuroplasticity of spinal cord in vivo, and caused the significant motor improvement, sensory recovery, and faster urinary reflex restoration in rats following SCI, while maintaining a highly favorable biosafety profile. Collectively, Spinor not only is a potentially clinical therapeutic paradigm as a living “exosome mothership” for revisiting Prometheus' Myth in SCI, but can be viewed allowing developmentally engineered manufacturing of biomimetic bio-assemblies with complex topology features and inbuilt biofunction attributes towards the regeneration of complex tissues including nervous system.
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Affiliation(s)
- Jin Yan
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Liqiang Zhang
- Institute for Stem Cell & Regenerative Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Liya Li
- Institute for Stem Cell & Regenerative Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Wangxiao He
- Institute for Stem Cell & Regenerative Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
- Department of Medical Oncology and Department of Talent Highland, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
- Corresponding author. Institute for Stem Cell & Regenerative Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
| | - Wenjia Liu
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
- Institute for Stem Cell & Regenerative Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
- Corresponding author. National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
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Li X, Feng L, Zhang C, Wang J, Wang S, Hu L. Insulin-like growth factor binding proteins 7 prevents dental pulp-derived mesenchymal stem cell senescence via metabolic downregulation of p21. SCIENCE CHINA. LIFE SCIENCES 2022; 65:2218-2232. [PMID: 35633481 DOI: 10.1007/s11427-021-2096-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 03/16/2022] [Indexed: 06/15/2023]
Abstract
Cellular senescence affects the efficacy of mesenchymal stem cells (MSCs)-mediated tissue regeneration. Insulin-like growth factor binding proteins-7 (IGFBP7), as a member of the IGF family, is associated with osteogenic differentiation and the senescence of MSCs, but its exact function and mechanism remain unclear. We found IGFBP7 promoted the osteogenic differentiation and prevented the senescence of dental pulp-derived MSCs (DPSCs), as observed in the gain-of-function and loss-of-function analyses, the senescence-associated marker p21 showed the most pronounced expression changes. We demonstrated that IGFBP7 activated the biological activity of SIRT1 deacetylase via metabolism, resulting in a deacetylation of H3K36ac and a decrease of the binding affinity of H3K36ac to p21 promoter, thereby reducing the transcription of p21, which ultimately prevents DPSCs senescence and promotes tissue regeneration. The activation of the mitochondrial electron transport chain (ETC) by Coenzyme Q10 could rescue the promotion of DPSC senescence induced by the knockdown of IGFBP7, whereas the inhibition of ETC by rotenone attenuated the prevention of DPSC senescence induced by IGFBP7 overexpression. In conclusion, our present results reveal a novel function of IGFBP7 in preventing DPSC senescence via the metabolism-induced deacetylation of H3K36ac and reduction of p21 transcription, suggesting that IGFBP7 is a potential target for promoting tissue regeneration in an aging environment.
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Affiliation(s)
- Xiaoyu Li
- Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health, Capital Medical University School of Stomatology, Beijing, 100050, China
| | - Liang Feng
- Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health, Capital Medical University School of Stomatology, Beijing, 100050, China
| | - Chunmei Zhang
- Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health, Capital Medical University School of Stomatology, Beijing, 100050, China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Jinsong Wang
- Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health, Capital Medical University School of Stomatology, Beijing, 100050, China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
- Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medicine, Beijing, 100069, China
| | - Songlin Wang
- Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health, Capital Medical University School of Stomatology, Beijing, 100050, China.
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
- Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medicine, Beijing, 100069, China.
- Laboratory for Oral and General Health Integration and Translation, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
- Research Unit of Tooth Development and Regeneration, Chinese Academy of Medical Sciences, Beijing, 100700, China.
| | - Lei Hu
- Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health, Capital Medical University School of Stomatology, Beijing, 100050, China.
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
- Laboratory for Oral and General Health Integration and Translation, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
- Research Unit of Tooth Development and Regeneration, Chinese Academy of Medical Sciences, Beijing, 100700, China.
- Department of Prosthodontics, Capital Medical University School of Stomatology, Beijing, 100050, China.
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Zhang J, Huang Y, Wang Y, Xu J, Huang T, Luo X. Construction of biomimetic cell-sheet-engineered periosteum with a double cell sheet to repair calvarial defects of rats. J Orthop Translat 2022; 38:1-11. [PMID: 36313975 PMCID: PMC9582589 DOI: 10.1016/j.jot.2022.09.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 08/31/2022] [Accepted: 09/09/2022] [Indexed: 11/06/2022] Open
Abstract
Background The periosteum plays a crucial role in the development and injury healing process of bone. The purpose of this study was to construct a biomimetic periosteum with a double cell sheet for bone tissue regeneration. Methods In vitro, the human amniotic mesenchymal stem cells (hAMSCs) sheet was first fabricated by adding 50 μg/ml ascorbic acid to the cell sheet induction medium. Characterization of the hAMSCs sheet was tested by general observation, microscopic observation, live/dead staining, scanning electron microscopy (SEM) and hematoxylin and eosin (HE) staining. Afterwards, the osteogenic cell sheet and vascular cell sheet were constructed and evaluated by general observation, alkaline phosphatase (ALP) staining, Alizarin Red S staining, SEM, live/dead staining and CD31 immunofluorescent staining for characterization. Then, we prepared the double cell sheet. In vivo, rat calvarial defect model was introduced to verify the regeneration of bone defects treated by different methods. Calvarial defects (diameter: 4 mm) were created of Sprague–Dawley rats. The rats were randomly divided into 4 groups: the control group, the osteogenic cell sheet group, the vascular cell sheet group and the double cell sheet group. Macroscopic, micro-CT and histological evaluations of the regenerated bone were performed to assess the treatment results at 8 weeks and 12 weeks after surgery. Results In vitro, hAMSCs sheet was successfully prepared. The hAMSCs sheet consisted of a large number of live hAMSCs and abundant extracellular matrix (ECM) that secreted by hAMSCs, as evidenced by macroscopic/microscopic observation, live/dead staining, SEM and HE staining. Besides, the osteogenic cell sheet and the vascular cell sheet were successfully prepared, which were verified by general observation, ALP staining, Alizarin Red S staining, SEM and CD31 immunofluorescent staining. In vivo, the macroscopic observation and micro-CT results both demonstrated that the double cell sheet group had better effect on bone regeneration than other groups. In addition, histological assessments indicated that large amounts of new bone had formed in the calvarial defects and more mature collagen in the double cell sheet group. Conclusion The double cell sheet could promote to repair calvarial defects of rats and accelerate bone regeneration. The translational potential of this article We successfully constructed a biomimetic cell-sheet-engineered periosteum with a double cell sheet by a simple, low-cost and effective method. This biomimetic periosteum may be a promising therapeutic strategy for the treatment of bone defects, which may be used in clinic in the future.
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Key Words
- Biomimetic periosteum
- Bone regeneration
- Double cell sheet
- Osteogenic cell sheet
- Trabecular number, Tb.N
- Trabecular thickness, Tb.Th
- Vascular cell sheet
- adiposetissue derivedstromalcells, ADSCs
- alkaline phosphatase, ALP
- bone mineral density, BMD
- bonemarrowmesenchymlstemcells, BMSCs
- bonevolume fraction, BV/TV
- cell sheet technology, CST
- cytokeratin 19, CK-19
- extracellular matrix, ECM
- hAMSCs sheet
- hematoxylin and eosin, HE
- human amniotic mesenchymal stem cells, hAMSCs
- human ethmoid sinus mucosa derived mesenchymal stem cells, hESMSCs
- periodontal ligament-derived cells, PDLCs
- polylactic-co-glycolic acid, PLGA
- scanning electron microscopy, SEM
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The Proangiogenic Potential of Rat Adipose-Derived Stromal Cells with and without Cell-Sheet Induction: A Comparative Study. Stem Cells Int 2022; 2022:2601764. [PMID: 36248258 PMCID: PMC9556194 DOI: 10.1155/2022/2601764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 07/31/2022] [Accepted: 09/05/2022] [Indexed: 11/18/2022] Open
Abstract
A functional vasculature for survival remains a challenge for tissue regeneration, which is indispensable for oxygen and nutrient supply. Utilizing mesenchymal stromal cells (MSCs) to alleviate tissue ischemia and repair dysfunctional or damaged endothelium is a promising strategy. Compared to other populations of MSCs, adipose-derived stromal cells (ASCs) possess a more significant proangiogenic potential and are abundantly available. Cell sheet technology has recently been widely utilized in bone engineering. Compared to conventional methods of seeding seed cell suspension onto biological scaffolds, cell sheet technology prevents cell loss and preserves the extracellular matrix (ECM). Nevertheless, the proangiogenic potential of ASC sheets remains unknown. In this study, rat ASC sheets were constructed, and their macro- and microstructures were examined. In addition, we investigated the effects of ASCs and ASC sheets on the biological properties and angiogenic capacity of endothelial cells (ECs). The results demonstrated that the ASC sheets gradually thickened as the number of cells and ECM increased over time and that the cells were in an active state of secretion. Similar to ASC-CM, the conditioned medium (CM) of ASC sheets could significantly enhance the proliferative capacity of ECs. ASC sheet-CM has significant advantages over ASC-CM in promoting the migration and angiogenesis of ECs, where the exosomes secreted by ASC sheets play an essential role. Therefore, using ASC sheets for therapeutic tissue and organ regeneration angiogenesis may be a valuable strategy.
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Wang Y, Zhang S, Yang H, Cao Y, Yu D, Zhao Y, Cao Y. MicroRNA-196a-5p overexpression in Wharton's jelly umbilical cord stem cells promotes their osteogenic differentiation and new bone formation in bone defects in the rat calvarium. Cell Tissue Res 2022; 390:245-260. [PMID: 35925405 DOI: 10.1007/s00441-022-03673-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 07/19/2022] [Indexed: 11/02/2022]
Abstract
The peri-tooth root alveolar loss often does not have sufficient space for repair material transplantation and plasticity. Mesenchymal stem cell (MSC) sheets have an advantage in providing more extracellular matrix (ECM) and may prove to be a new therapeutic consideration for this bone defect repair. The identification of key regulators that stimulate MSCs' osteogenic potential and sheet-derived ECM deposition is the key to promoting its application. In this study, we found that inhibition or overexpression of miR-196a-5p led to a decline or enhancement, respectively, in the alkaline phosphatase (ALP) activity, mineralization, and the levels of osteogenic markers, Osteocalcin (OCN), Dentin Matrix Protein 1 (DMP1), Bone Sialoprotein (BSP), and Dentin Sialophosphoprotein (DSPP) of Wharton's jelly of umbilical cord stem cells (WJCMSCs) in vitro. Moreover, the 5,6-Carboxyfluorescein Diacetate Succinimidyl Ester (CFSE) analysis revealed inhibition of the WJCMSCs' proliferative ability upon miR-196a-5p overexpression. Characterization of the sheet formation by picrosirius red and Masson staining indicated that miR-196a-5p overexpression significantly promoted the collagen content in whole WJCMSC sheet-derived ECM. Furthermore, micro-CT and histopathology results indicated that the miR-196a-5p-overexpressed WJCMSC sheets significantly promoted new bone regeneration and rat calvarial bone defect closure 12 weeks following transplantation. The mRNA microarray analysis of miR-196a-5p-overexpressed WJCMSCs revealed 959 differentially expressed genes (DEGs) (34 upregulated and 925 downregulated). Moreover, 241 genes targeted by miR-196a-5p were predicted by using miRNA function websites of which only 19 predicted genes were consistent with the microarray revealed DEGs. Hence, one unrevealed downregulated DEG Serpin Family B Member 2 (SERPINB2) was investigated. And the deletion of SERPINB2 enhanced the ALP activity and mineralization of WJCMSCs in vitro. In conclusion, our study found that miR-196a-5p, as a key regulator, could repress the proliferation tendency, while stimulating osteogenic ability and WJCMSC sheet-derived ECM deposition, thus promoting new bone formation and rat calvarial bone defect closure. Furthermore, SERPINB2 is a key downstream gene involved in the miR-196a-5p-promoted WJCMSC osteogenesis.
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Affiliation(s)
- Yantong Wang
- Department of General Dentistry, Capital Medical University School of Stomatology, Beijing, 100050, China.,Laboratory of Molecular Signaling and Stem Cells TherapyKey Laboratory of Tooth Regeneration and Function ReconstructionDongcheng District, Capital Medical University School of Stomatology, 4 Tiantanxili, BeijingBeijing, 100050, China
| | - Simin Zhang
- Department of General Dentistry, Capital Medical University School of Stomatology, Beijing, 100050, China
| | - Haoqing Yang
- Laboratory of Molecular Signaling and Stem Cells TherapyKey Laboratory of Tooth Regeneration and Function ReconstructionDongcheng District, Capital Medical University School of Stomatology, 4 Tiantanxili, BeijingBeijing, 100050, China
| | - Yangyang Cao
- Laboratory of Molecular Signaling and Stem Cells TherapyKey Laboratory of Tooth Regeneration and Function ReconstructionDongcheng District, Capital Medical University School of Stomatology, 4 Tiantanxili, BeijingBeijing, 100050, China
| | - Dianqin Yu
- Department of General Dentistry, Capital Medical University School of Stomatology, Beijing, 100050, China
| | - Yingchu Zhao
- Department of General Dentistry, Capital Medical University School of Stomatology, Beijing, 100050, China
| | - Yu Cao
- Department of General Dentistry, Capital Medical University School of Stomatology, Beijing, 100050, China. .,Laboratory of Molecular Signaling and Stem Cells TherapyKey Laboratory of Tooth Regeneration and Function ReconstructionDongcheng District, Capital Medical University School of Stomatology, 4 Tiantanxili, BeijingBeijing, 100050, China.
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Yuan SM, Yang XT, Zhang SY, Tian WD, Yang B. Therapeutic potential of dental pulp stem cells and their derivatives: Insights from basic research toward clinical applications. World J Stem Cells 2022; 14:435-452. [PMID: 36157522 PMCID: PMC9350620 DOI: 10.4252/wjsc.v14.i7.435] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 05/25/2022] [Accepted: 06/20/2022] [Indexed: 02/06/2023] Open
Abstract
For more than 20 years, researchers have isolated and identified postnatal dental pulp stem cells (DPSCs) from different teeth, including natal teeth, exfoliated deciduous teeth, healthy teeth, and diseased teeth. Their mesenchymal stem cell (MSC)-like immunophenotypic characteristics, high proliferation rate, potential for multidirectional differentiation and biological features were demonstrated to be superior to those of bone marrow MSCs. In addition, several main application forms of DPSCs and their derivatives have been investigated, including stem cell injections, modified stem cells, stem cell sheets and stem cell spheroids. In vitro and in vivo administration of DPSCs and their derivatives exhibited beneficial effects in various disease models of different tissues and organs. Therefore, DPSCs and their derivatives are regarded as excellent candidates for stem cell-based tissue regeneration. In this review, we aim to provide an overview of the potential application of DPSCs and their derivatives in the field of regenerative medicine. We describe the similarities and differences of DPSCs isolated from donors of different ages and health conditions. The methodologies for therapeutic administration of DPSCs and their derivatives are introduced, including single injections and the transplantation of the cells with a support, as cell sheets, or as cell spheroids. We also summarize the underlying mechanisms of the regenerative potential of DPSCs.
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Affiliation(s)
- Sheng-Meng Yuan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, 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
| | - Xue-Ting Yang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, 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
| | - Si-Yuan Zhang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Wei-Dong Tian
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, 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
| | - Bo Yang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Engineering Research Center of Oral Translational Medicine, National Engineering Laboratory for Oral Regenerative Medicine, 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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Huang G, Xia B, Dai Z, Yang R, Chen R, Yang H. Comparative study of DFAT cell and ADSC sheets for periodontal tissue regeneration:
in vivo
and
in vitro
evidence. J Clin Periodontol 2022; 49:1289-1303. [PMID: 35851962 DOI: 10.1111/jcpe.13705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 05/29/2022] [Accepted: 06/30/2022] [Indexed: 11/27/2022]
Affiliation(s)
- Guobin Huang
- Yunnan Key Laboratory of Stomatology Kunming Medical University Kunming Yunnan PR China
- Department of Dental Research The Affiliated Stomatology Hospital of Kunming Medical University Kunming Yunnan PR China
| | - Bin Xia
- Yunnan Key Laboratory of Stomatology Kunming Medical University Kunming Yunnan PR China
- Department of Oral and Maxillofacial Surgery The Affiliated Stomatological Hospital of Kunming Medical University Kunming Yunnan P.R. China
| | - Zichao Dai
- Yunnan Key Laboratory of Stomatology Kunming Medical University Kunming Yunnan PR China
- Department of Dental Research The Affiliated Stomatology Hospital of Kunming Medical University Kunming Yunnan PR China
| | - Rongqiang Yang
- Yunnan Key Laboratory of Stomatology Kunming Medical University Kunming Yunnan PR China
- Department of Dental Research The Affiliated Stomatology Hospital of Kunming Medical University Kunming Yunnan PR China
| | - Rui Chen
- Yunnan Key Laboratory of Stomatology Kunming Medical University Kunming Yunnan PR China
- Department of Dental Research The Affiliated Stomatology Hospital of Kunming Medical University Kunming Yunnan PR China
| | - Hefeng Yang
- Yunnan Key Laboratory of Stomatology Kunming Medical University Kunming Yunnan PR China
- Department of Dental Research The Affiliated Stomatology Hospital of Kunming Medical University Kunming Yunnan PR China
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Yi YY, Zhang SB, Chen H, Xu HW, Wang SJ. Ascorbic acid promotes nucleus pulposus cell regeneration by regulating proliferation during intervertebral disc degeneration. J Nutr Biochem 2022; 108:109099. [PMID: 35779794 DOI: 10.1016/j.jnutbio.2022.109099] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 03/07/2022] [Accepted: 06/08/2022] [Indexed: 11/18/2022]
Abstract
Intervertebral disc degeneration (IVDD) affects human health. Ascorbic acid (AA) deficiency is a major factor that contributes to the development of degenerative disc disease in the elderly. Here, as a novel treatment with promising applications, we demonstrate that AA treatment inhibited senescence and maintained the proliferation of nucleus pulposus (NP) cells during long-term culture. AA-treated NP cells and acupuncture-treated rat models exhibited degenerative resistance during cell passaging and AA increased cell proliferation and decreased time-related senescence. Interestingly, Kyoto Encyclopedia of Genes and Genomes pathway mapping revealed five top enriched pathways and four pathways were associated with the aldehyde dehydrogenase (ALDH) enzyme family, especially proliferation-related ALDH1A3. Collectively, our findings demonstrate that ALDH1A3 expression was increased by AA treatment, which counteracted degeneration in NP cells over time and rejuvenated maintenance of proliferation in NP cells, which has a promising therapeutic implications in IVDD.
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Affiliation(s)
- Yu-Yang Yi
- Department of Spinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China
| | - Shu-Bao Zhang
- Department of Spinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China
| | - Hao Chen
- Department of Spinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China
| | - Hao-Wei Xu
- Department of Spinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China
| | - Shan-Jin Wang
- Department of Spinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China; Department of orthopedic, East Hospital, Ji'an Hospital, Jinggangshan University School of Medicine, Jiangxi, China.
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hAMSC Sheet Promotes Repair of Rabbit Osteochondral Defects. Stem Cells Int 2022; 2022:3967722. [PMID: 35400134 PMCID: PMC8989589 DOI: 10.1155/2022/3967722] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 08/18/2021] [Accepted: 03/15/2022] [Indexed: 01/08/2023] Open
Abstract
Osteochondral lesion is clinically common disease, which has been recognized as one of the contributing factors of significant morbidity. Although current treatments have achieved good outcomes, some undesirable complications and failures are not uncommon. Cell sheet technology (CST), an innovative technology to harvest seed cells and preserve abundant ECM, has been widely used in various tissue regeneration. For osteochondral lesion, many studies focus on using CST to repair osteochondral lesion and have achieved good outcomes. In the previous study, we have demonstrated that hAMSC sheet had a positive effect on osteochondral lesion. Therefore, this study is aimed at comparing the effect of noninduced hAMSC sheet with chondrogenically induced hAMSC sheet on osteochondral lesion and cartilage regeneration.
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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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45
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Mechanical force-sensitive lncRNA SNHG8 inhibits osteogenic differentiation by regulating EZH2 in hPDLSCs. Cell Signal 2022; 93:110285. [DOI: 10.1016/j.cellsig.2022.110285] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 02/12/2022] [Accepted: 02/17/2022] [Indexed: 12/18/2022]
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Safi IN, Hussein BMA, Al-Shammari AM. Bio-hybrid dental implants prepared using stem cells with β-TCP-coated titanium and zirconia. J Periodontal Implant Sci 2022; 52:242-257. [PMID: 35775699 PMCID: PMC9253282 DOI: 10.5051/jpis.2006080304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 09/07/2021] [Accepted: 10/20/2021] [Indexed: 11/08/2022] Open
Abstract
Purpose This study investigated periodontal ligament (PDL) restoration in osseointegrated implants using stem cells. Methods Commercial pure titanium and zirconium oxide (zirconia) were coated with beta-tricalcium phosphate (β-TCP) using a long-pulse Nd:YAG laser (1,064 nm). Isolated bone marrow mesenchymal cells (BMMSCs) from rabbit tibia and femur, isolated PDL stem cells (PDLSCs) from the lower right incisor, and co-cultured BMMSCs and PDLSCs were tested for periostin markers using an immunofluorescent assay. Implants with 3D-engineered tissue were implanted into the lower right central incisors after extraction from rabbits. Forty implants (Ti or zirconia) were subdivided according to the duration of implantation (healing period: 45 or 90 days). Each subgroup (20 implants) was subdivided into 4 groups (without cells, PDLSC sheets, BMMSC sheets, and co-culture cell sheets). All groups underwent histological testing involving haematoxylin and eosin staining and immunohistochemistry, stereoscopic analysis to measure the PDL width, and field emission scanning electron microscopy (FESEM). The natural lower central incisors were used as controls. Results The BMMSCs co-cultured with PDLSCs generated a well-formed PDL tissue that exhibited positive periostin expression. Histological analysis showed that the implantation of coated (Ti and zirconia) dental implants without a cell sheet resulted in a well-osseointegrated implant at both healing intervals, which was confirmed with FESEM analysis and negative periostin expression. The mesenchymal tissue structured from PDLSCs only or co-cultured (BMMSCs and PDLSCs) could form a natural periodontal tissue with no significant difference between Ti and zirconia implants, consequently forming a biohybrid dental implant. Green fluorescence for periostin was clearly detected around the biohybrid implants after 45 and 90 days. FESEM showed the invasion of PDL-like fibres perpendicular to the cementum of the bio-hybrid implants. Conclusions β-TCP-coated (Ti and zirconia) implants generated periodontal tissue and formed biohybrid implants when mesenchymal-tissue-layered cell sheets were isolated from PDLSCs alone or co-cultured BMMSCs and PDLSCs.
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Affiliation(s)
- Ihab Nabeel Safi
- Prosthetics Department, Collage of Dentistry, University of Baghdad, Baghdad, Iraq
| | | | - Ahmed Majeed Al-Shammari
- Experimental Therapy Department, Iraqi Center for Cancer and Medical Genetic Research, Mustansiriyah University, Baghdad, Iraq
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Weng Z, Wang Y, Ouchi T, Liu H, Qiao X, Wu C, Zhao Z, Li L, Li B. OUP accepted manuscript. Stem Cells Transl Med 2022; 11:356-371. [PMID: 35485439 PMCID: PMC9052415 DOI: 10.1093/stcltm/szac004] [Citation(s) in RCA: 122] [Impact Index Per Article: 40.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 12/19/2021] [Indexed: 11/14/2022] Open
Affiliation(s)
| | | | - Takehito Ouchi
- Department of Physiology, Tokyo Dental College, Tokyo, Japan
| | - Hanghang Liu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China
| | - Xianghe Qiao
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China
| | - Chenzhou Wu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China
| | - Zhihe Zhao
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China
| | - Longjiang Li
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China
| | - Bo Li
- Corresponding author: Bo Li, DDS, PhD, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, No.14, 3rd Section of Ren Min Nan Rd. Chengdu, Sichuan 610041, People’s Republic of China.
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In focus in HCB. Histochem Cell Biol 2021; 156:405-408. [PMID: 34729665 DOI: 10.1007/s00418-021-02044-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Tsoukalas D, Buga AM, Docea AO, Sarandi E, Mitrut R, Renieri E, Spandidos DA, Rogoveanu I, Cercelaru L, Niculescu M, Tsatsakis A, Calina D. Reversal of brain aging by targeting telomerase: A nutraceutical approach. Int J Mol Med 2021; 48:199. [PMID: 34515324 PMCID: PMC8448543 DOI: 10.3892/ijmm.2021.5032] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 09/07/2021] [Indexed: 12/17/2022] Open
Abstract
Telomeres, the protective caps of chromosomes, shorten with age, as telomerase, the enzyme responsible for the compensation of telomere erosion, is inactive in the majority of cells. Telomere shortening and subsequent cell senescence lead to tissue aging and age‑related diseases. Neurodegenerative disorders, characterized by the progressive loss of neurons among other hallmarks of aged tissue, and poor cognitive function, have been associated with a short telomere length. Thus, telomerase activity has emerged as a therapeutic target, with novel agents being under investigation. The present study aimed to examine the effects of a novel natural telomerase activator, 'Reverse™', containing Centella asiatica extract, vitamin C, zinc and vitamin D3 on the brains of 18‑month‑old rats. The administration of the 'Reverse™' supplement for 3 months restored telomerase reverse transcriptase (TERT) expression in the brains of rats, as revealed by ELISA and immunohistochemistry. In addition, the findings from PCR‑ELISA demonstrated an enhanced telomerase activity in the cerebellum and cortex cells in the brains of rats treated with the 'Reverse™' supplement. The histopathological findings confirmed a structural reversibility effect close to the differentiation observed in the young control group of rats treated with two capsules/kg body weight of the 'Reverse™' supplement. On the whole, the findings of the present study provide a strong indication that an increased telomerase activity and TERT expression may be achieved not only in the postnatal or embryonic period, but also in the brains of middle‑aged rats through nutraceutical supplementation. The use of the 'Reverse™' supplement may thus contribute to the potential alleviation of a number of central nervous system diseases.
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Affiliation(s)
- Dimitris Tsoukalas
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- Metabolomic Medicine, Health Clinic for Autoimmune and Chronic Diseases, 10674 Athens, Greece
- European Institute of Nutritional Medicine (E.I.Nu.M.), I-00198 Rome, Italy
| | - Ana Maria Buga
- Department of Biochemistry, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Evangelia Sarandi
- Metabolomic Medicine, Health Clinic for Autoimmune and Chronic Diseases, 10674 Athens, Greece
- Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003 Heraklion, Greece
| | - Radu Mitrut
- Department of Cardiology, University and Emergency Hospital, 050098 Bucharest, Romania
| | - Elisavet Renieri
- Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003 Heraklion, Greece
- Environmental Engineering Laboratory, Department of Chemical Engineering, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Demetrios A. Spandidos
- Laboratory of Clinical Virology, Medical School, University of Crete, 71409 Heraklion, Greece
| | - Ion Rogoveanu
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Liliana Cercelaru
- Department of Anatomy and Embryology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Mihaela Niculescu
- Department of Anatomy and Embryology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Aristidis Tsatsakis
- Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003 Heraklion, Greece
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Song YT, Liu PC, Tan J, Zou CY, Li QJ, Li-Ling J, Xie HQ. Stem cell-based therapy for ameliorating intrauterine adhesion and endometrium injury. Stem Cell Res Ther 2021; 12:556. [PMID: 34717746 PMCID: PMC8557001 DOI: 10.1186/s13287-021-02620-2] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 10/04/2021] [Indexed: 02/08/2023] Open
Abstract
Intrauterine adhesion refers to endometrial repair disorders which are usually caused by uterine injury and may lead to a series of complications such as abnormal menstrual bleeding, recurrent abortion and secondary infertility. At present, therapeutic approaches to intrauterine adhesion are limited due to the lack of effective methods to promote regeneration following severe endometrial injury. Therefore, to develop new methods to prevent endometrial injury and intrauterine adhesion has become an urgent need. For severely damaged endometrium, the loss of stem cells in the endometrium may affect its regeneration. This article aimed to discuss the characteristics of various stem cells and their applications for uterine tissue regeneration.
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Affiliation(s)
- Yu-Ting Song
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Peng-Cheng Liu
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jie Tan
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Chen-Yu Zou
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Qian-Jin Li
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jesse Li-Ling
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
- Department of Medical Genetics, West China Second Hospital, Sichuan University, Chengdu, 610041, China
| | - Hui-Qi Xie
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
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