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Stieger RB, Lilaj B, Hönigl GP, Pock S, Cvikl B. Flow Cytometry Illuminates Dental Stem Cells: a Systematic Review of Immunomodulatory and Regenerative Breakthroughs. Stem Cell Rev Rep 2025:10.1007/s12015-025-10883-y. [PMID: 40279028 DOI: 10.1007/s12015-025-10883-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2025] [Indexed: 04/26/2025]
Abstract
BACKGROUND Dental stem cells hold significant potential in regenerative medicine due to their multipotency, accessibility, and immunomodulatory effects. Flow cytometry is a critical tool for analyzing these cells, particularly in identifying and characterizing immunomodulatory markers that enhance their clinical applications. This systematic review aims to answer the question: "How does flow cytometry facilitate the identification and characterization of immunomodulatory markers in dental stem cells to enhance their application in regenerative medicine?". METHODS An exhaustive literature search was conducted in PubMed, retrieving 430 studies, of which 284 met inclusion criteria. Studies were selected based on the use of flow cytometry to analyze immunomodulatory markers in dental stem cells, focusing on methodologies, key findings, and challenges. RESULTS Of the 284 articles, 229 employed flow cytometry, with 115 reporting relevant results. Flow cytometry revealed important insights into the immunological interactions of various dental stem cells, including dental pulp stem cells, stem cells from human exfoliated deciduous teeth, periodontal ligament stem cells, and stem cells from the apical papilla, by identifying and characterizing immunomodulatory markers such as PD-L1, IDO, and TGF-β1. CONCLUSIONS Flow cytometry is essential for advancing the understanding of dental stem cells' immunomodulatory properties. Standardization of methodologies is required to overcome technical challenges and enhance the clinical applications of dental stem cells in regenerative medicine and immunotherapy.
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Affiliation(s)
- Robert B Stieger
- Department of Conservative Dentistry, Sigmund Freud University, Vienna, Austria.
| | - Bledar Lilaj
- Department of Conservative Dentistry, Sigmund Freud University, Vienna, Austria
| | - Gernot P Hönigl
- Department of Conservative Dentistry, Sigmund Freud University, Vienna, Austria
| | - Sophie Pock
- Department of Conservative Dentistry, Sigmund Freud University, Vienna, Austria
| | - Barbara Cvikl
- Department of Conservative Dentistry, Sigmund Freud University, Vienna, Austria.
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Li Y, Song G, Jiang Y, Zhao H, Zhu Y, Song S, Wang L, Wu X. Single-cell transcriptome analysis of stem cells from human exfoliated deciduous teeth investigating functional heterogeneity in immunomodulation. Sci Rep 2024; 14:31279. [PMID: 39732760 PMCID: PMC11682124 DOI: 10.1038/s41598-024-82734-8] [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: 08/29/2024] [Accepted: 12/09/2024] [Indexed: 12/30/2024] Open
Abstract
Mesenchymal stem cells (MSCs) have been widely used in the treatment of various inflammatory diseases. The inadequate understanding of MSCs and their heterogeneity can impact the immune environment, which may be the cause of the good outcomes of MSCs-based therapy that cannot always be achieved. Recently, stem cells from human exfoliated deciduous teeth (SHED) showed great potential in inflammatory and autoimmune diseases due to their immature properties compared with MSCs. In our study, single-cell RNA sequencing (scRNA-seq) revealed that SHED in a low differentiation state (S7) exhibited the powerful ability to recruit multiple immune cells. In contrast, SHED in a relatively high differentiation state (S1) may hold a solid ability to secret many factors with paracrine signaling capacity. The analysis result shows that SHED has more robust immunomodulatory properties than human bone marrow-derived mesenchymal stem cells (hBMSCs) or human umbilical cord-derived mesenchymal stem cells (hUCMSCs). When co-cultured with PBMCs, SHED can enhance the proliferation of Treg and down-regulate TNF-α in vitro. SHED may have some advantages in the treatment of inflammatory and autoimmune diseases.
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Affiliation(s)
- Yin Li
- Department of Stomatology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, China.
- Beijing Engineering Research Center of Immunocellular Therapy, Beijing, China.
| | - Guangyuan Song
- Beijing Engineering Research Center of Immunocellular Therapy, Beijing, China
| | - Yu Jiang
- Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
| | - Haitao Zhao
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
| | - Yizhun Zhu
- School of Pharmacy, Human Phenome Institute, Fudan University, Shanghai, 201203, China
- State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau, China
| | - Shanshan Song
- Beijing Engineering Research Center of Immunocellular Therapy, Beijing, China
| | - Lulu Wang
- Beijing Engineering Research Center of Immunocellular Therapy, Beijing, China
| | - Xueying Wu
- Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
- Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
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Zhang H, Jiang Z, Ye Y, Pan Y, Yu M, Yang G, Wang Y. Mesenchymal stem cells derived from hard palate: An attractive alternative for regenerative medicine. Oral Dis 2024; 30:4145-4151. [PMID: 39007203 DOI: 10.1111/odi.15043] [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: 11/02/2023] [Revised: 04/21/2024] [Accepted: 06/04/2024] [Indexed: 07/16/2024]
Abstract
OBJECTIVE The palatal mucosa exhibits a notable ability to regenerate without causing scarring during the process of wound healing, rendering it a highly valuable reservoir of mesenchymal stem cells (MSCs). The aim of this review is to summarize the different sources of MSCs derived from hard palatal (PMSCs), thereby presenting a promising avenue for the utilization of regenerative medicine. MATERIALS AND METHODS Pertinent literatures focused on the sources, identification methods, and advantageous characteristics of PMSCs are obtained from PubMed and Web of Science. RESULTS PMSCs, originating from the hard palate periosteum, subepithelial adipose tissue, and lamina propria, have been successfully isolated and characterized, with positive markers for MSCs and negative markers for hematopoietic stem cells. Moreover, PMSCs demonstrate resistance to inflammatory stimuli, enabling uninterrupted osteogenesis in the presence of inflammation. Additionally, PMSCs possess a notable migratory capacity, facilitating prompt arrival at the site of injury. Furthermore, PMSCs exhibit various advantageous inherent in stem cells, including clonogenicity, self-renewal capability, and pluripotent differentiation potential. CONCLUSIONS PMSCs have stem cell-related properties and can be used for regenerative medicine of cells and tissues in the future.
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Affiliation(s)
- Hui Zhang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
| | - Zhiwei Jiang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
| | - Yuer Ye
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
| | - Yiqi Pan
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
| | - Mengjia Yu
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
| | - Guoli Yang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
| | - Ying Wang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
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Li Z, Li J, Dai S, Liu R, Guo Q, Liu F. Research Status and Trends in Periodontal Ligament Stem Cells: A Bibliometric Analysis over the Past Two Decades. Stem Cells Int 2024; 2024:9955136. [PMID: 39372680 PMCID: PMC11452234 DOI: 10.1155/2024/9955136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 08/21/2024] [Accepted: 08/31/2024] [Indexed: 10/08/2024] Open
Abstract
Objective Currently, the summaries of research on periodontal ligament stem cells (PDLSCs) are mainly reviews, and the systematic evaluation of all relevant studies is lacking. The aim of our study was to reveal the research status and developmental trends of PDLSCs using bibliometric analyses. Methods Publications on PDLSC from 2004 to 2023 in the PubMed database were searched and then screened according to certain inclusion and exclusion criteria. Two researchers browsed the included papers and recorded information such as the research type and research model. The VOSviewer software was used to analyze the distribution of authors, journals, and institutions. The contents and directions of PDLSC research were summarized by analyzing high-frequency keywords. The CiteSpace software was used to monitor burst words, determine hot factors, and indicate developmental trends. Results During the past two decades, the number of studies on PDLSCs increased. China published the most related papers. The primary type of article was basic research. Among core journals, the Journal of Periodontal Research had the highest number of publications. The Fourth Military Medical University (China) was leading in the number of articles on PDLSCs. Research topics mainly included mechanism of periodontal diseases, tissue engineering and regeneration, biological characteristics of PDLSCs, and comparison with other stem cells. Infectious inflammation and mechanical stimulation were important pathological conditions and research topics. Conclusion The research of PDLSCs is still in a rapid development stage. Our study provides new insights into the current research status and future trend in this field.
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Affiliation(s)
- Zhengyang Li
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
- Department of Pediatric DentistryCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
| | - Jinyi Li
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
- Department of Pediatric DentistryCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
| | - Shanshan Dai
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
- Department of Pediatric DentistryCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
| | - Ruirui Liu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
- Department of ProsthodonticsCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
| | - Qingyu Guo
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
- Department of Pediatric DentistryCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
| | - Fei Liu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
- Department of Pediatric DentistryCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
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Rajpurohit K, Dodwad V, Kharat A, Belludi S, Pharne P, Marium S. Influence of surface texture on osteogenic differentiation of dental pulp stem cells: An in vitro study. J Indian Soc Periodontol 2024; 28:478-483. [PMID: 40018713 PMCID: PMC11864341 DOI: 10.4103/jisp.jisp_307_23] [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: 06/14/2023] [Revised: 12/19/2024] [Accepted: 12/20/2024] [Indexed: 03/01/2025] Open
Abstract
Background In comparison with perfectly machined surface implants, surface topographic modifications like roughness accelerate the osteogenesis of dental pulpal stem cells (DPSC). This greatly enhances bone-implant contact and osteogenic potential of the stem cells. Hence, the aim of the current study was to evaluate and compare the differentiation and proliferation potential of stem cells obtained from dental pulp on sand-blasted and acid etched implant discs surfaces. Materials and Methods Stem cells from dental pulp were extracted from the premolar region of oral cavity. Titanium discs that measured one centimeter in diameter and three millimetres in thickness were used as investigation surfaces. Titanium surface disc were acid etched and sandblasted. Investigation had three group: acid etched (Group A), sandblasted (Group B), and standard control group, i.e., cells treated with osteogenic induction media only (Group C). In Group C, mesenchymal stem cells (MSCs) were treated with osteogenic induction medium without any titanium disc and these cells were used as standard controls. To identify which modified implant surface had greater potential for proliferation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed using the explant culture. MTT assay assessed the viability of the cells as a function of its redox potential. This was followed by recognition of the stem cells for CD90, CD73, and CD 105 markers using flow cytometry with RUNX2 antibody on days 7 and 21 of incubation. The isolated cells were stained using 1% alizarin red stain to identify the number of stem cells per square centimeter area under the light microscope. Results The osteogenic differentiation of both the materials was compared with standard control (MSCs treated with osteogenic differentiation media only). The osteoblastic cells on the acid-etched and sand-blasted implant surface disc had an almost identical capacity for proliferation till the MTT assay but according to the results of the alizarin red staining there was a slightly higher proliferation potential on acid etched surfaces compared to the sand blasted surfaces. Therefore, acid etched surfaces showed higher potential of osteogenic differentiation of DPSCs compared with sand-blasted surfaces. Conclusion In comparison with perfectly machined surface implants, topographic surface modifications such as roughness can accelerate the osteogenesis of DPSC in vitro.
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Affiliation(s)
- Komal Rajpurohit
- Department of Periodontology, Bharati Vidyapeeth (Deemed to be University) Dental college and Hospital, Pimpri, Pune, Maharashtra, India
| | - Vidya Dodwad
- Department of Periodontology, Bharati Vidyapeeth (Deemed to be University) Dental college and Hospital, Pimpri, Pune, Maharashtra, India
| | - Avinash Kharat
- Regenerative Medicine Laboratory, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
| | - Spoorthi Belludi
- Department of Periodontology, K.L.E Society of Dental Sciences, Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka, India
| | - Pooja Pharne
- Department of Periodontology, Bharati Vidyapeeth (Deemed to be University) Dental college and Hospital, Pimpri, Pune, Maharashtra, India
| | - Sarah Marium
- Department of Periodontology, Bharati Vidyapeeth (Deemed to be University) Dental college and Hospital, Pimpri, Pune, Maharashtra, India
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Suciu TS, Feștilă D, Berindan-Neagoe I, Nutu A, Armencea G, Aghiorghiesei AI, Vulcan T, Băciuț M. Circular RNA-Mediated Regulation of Oral Tissue-Derived Stem Cell Differentiation: Implications for Oral Medicine and Orthodontic Applications. Stem Cell Rev Rep 2024; 20:656-671. [PMID: 38279054 PMCID: PMC10984898 DOI: 10.1007/s12015-024-10683-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/16/2024] [Indexed: 01/28/2024]
Abstract
Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs (ncRNAs) which unlike linear RNAs, have a covalently closed continuous loop structure. circRNAs are found abundantly in human cells and their biology is complex. They feature unique expression to different types of cells, tissues, and developmental stages. To the present, the functional roles of circular RNAs are not fully understood. They reportedly act as microRNA (miRNA) sponges, therefore having key regulatory functions in diverse physiological and pathological processes. As for dentistry field, lines of evidence indicate that circRNAs play vital roles in the odontogenic and osteogenic differentiation of dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs). Abnormal expression of circRNAs have been found in other areas of pathology frequently reflected also in the oral environment, such as inflammation or bone and soft tissue loss. Therefore, circRNAs could be of significant importance in various fields in dentistry, especially in bone and soft tissue engineering and regeneration. Understanding the molecular mechanisms occurring during the regulation of oral biological and tissue remodeling processes could augment the discovery of novel diagnostic biomarkers and therapeutic strategies that will improve orthodontic and other oral therapeutic protocols.
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Affiliation(s)
- Tudor-Sergiu Suciu
- Department of Orthodontics and Dentofacial Orthopedics, Iuliu Hațieganu University of Medicine and Pharmacy, 400083, Cluj-Napoca, Romania
| | - Dana Feștilă
- Department of Orthodontics and Dentofacial Orthopedics, Iuliu Hațieganu University of Medicine and Pharmacy, 400083, Cluj-Napoca, Romania.
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, 400337, Cluj-Napoca, Romania
| | - Andreea Nutu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, 400337, Cluj-Napoca, Romania
| | - Gabriel Armencea
- Department of Maxillofacial Surgery and Implantology, Iuliu Hațieganu University of Medicine and Pharmacy, 400029, Cluj-Napoca, Romania
| | - Alexandra Iulia Aghiorghiesei
- Department of Prosthodontics and Dental Materials, Iuliu Hațieganu University of Medicine and Pharmacy, 400006, Cluj-Napoca, Romania
| | - Talida Vulcan
- Department of Dermatology, Iuliu Hațieganu University of Medicine and Pharmacy, 400006, Cluj-Napoca, Romania
| | - Mihaela Băciuț
- Department of Maxillofacial Surgery and Implantology, Iuliu Hațieganu University of Medicine and Pharmacy, 400029, Cluj-Napoca, Romania
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Ptasiewicz M, Orłowski M, Magryś A, Kocki J, Gosik K, Stachurski P, Chałas R. Apoptosis Regulation in Dental Pulp Cells and PD-1/PD-L1 Expression Dynamics Under Ozone Exposure - A Pilot Approach. Arch Immunol Ther Exp (Warsz) 2024; 72:aite-2024-0019. [PMID: 39277882 DOI: 10.2478/aite-2024-0019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 08/12/2024] [Indexed: 09/17/2024]
Abstract
This study aimed to determine the effect of ozone on the expression of Bax and Bcl-2 genes in dental pulp cells. Additionally, the programmed cell death protein 1, programmed death-ligand 1, and CD200 antigens were determined in lymphocytes to assess their surface expression. Dental pulp cells were cultured from extracted healthy third molars and characterized as dental pulp stromal cells. Gene expression of Bcl-2 and Bax was analyzed at 0 s, 6 s, and 12 s of ozone exposure using real-time PCR. Lymphocytes from dental pulp were subjected to ozone exposure for 12 s and PD-1, PD-L1, and CD200/CD200R expression was analyzed by flow cytometry. Upon exposure to ozone for 6 s, the Bcl-2 expression decreased significantly to -0.09, and at 12 s, it increased significantly to 0.3. Bax gene expression level increased significantly to 0.188 after 6 s exposure, and at 12 s, to 0.16. Lymphocytes exposed to ozone for 12 s showed minimal changes in PD-1, PD-L1, and CD200/CD200R expression levels, indicating that oxidative stress does not impact the signaling pathways regulating these molecules. The significant upregulation of Bcl-2 at 12 s highlights the cells' effort to protect themselves from prolonged oxidative stress, possibly tipping the balance toward cell survival and tissue repair. However, the absence of changes in PD-1 and PD-L1 expression on lymphocytes under oxidative stress suggests that these molecules are not sensitive to oxidative stress in this context.
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Affiliation(s)
- Maja Ptasiewicz
- Department of Oral Medicine, Medical University of Lublin, Lublin, Poland
| | - Mirosław Orłowski
- Department of Conservative Dentistry with Endodontics, Medical University of Lublin, Lublin, Poland
| | - Agnieszka Magryś
- Chair and Department of Medical Microbiology, Medical University of Lublin, Lublin, Poland
| | - Janusz Kocki
- Department of Clinical Genetics, Medical University of Lublin, Lublin, Poland
| | - Krzysztof Gosik
- Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Lublin, Poland
| | - Piotr Stachurski
- Department of Pediatric Dentistry, Medical University of Lublin, Lublin, Poland
| | - Renata Chałas
- Department of Oral Medicine, Medical University of Lublin, Lublin, Poland
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Luo H, Birjandi AA, Ren F, Sun T, Sharpe PT, Sun H, An Z. Advances in oral mesenchymal stem cell-derived extracellular vesicles in health and disease. Genes Dis 2024; 11:346-357. [PMID: 37588220 PMCID: PMC10425856 DOI: 10.1016/j.gendis.2023.03.015] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 03/08/2023] [Accepted: 03/15/2023] [Indexed: 08/18/2023] Open
Abstract
Extracellular vesicles (EVs) are nano-size vesicles secreted naturally by all cells into the extracellular space and have been recognized as important cell-cell mediators in multicellular organisms. EVs contain nucleic acids, proteins, lipids, and other cellular components, regulating many basic biological processes and playing an important role in regenerative medicine and diseases. EVs can be traced to their cells of origin and exhibit a similar function. Moreover, EVs demonstrate low immunogenicity, good biocompatibility, and fewer side effects, compared to their parent cells. Mesenchymal stem cells (MSCs) are one of the most important resource cells for EVs, with a great capacity for self-renewal and multipotent differentiation, and play an essential role in stem cell therapy. The mechanism of MSC therapy was thought to be attributed to the differentiation of MSCs after targeted migration, as previously noted. However, emerging evidence shows the previously unknown role of MSC-derived paracrine factors in stem cell therapy. Especially EVs derived from oral tissue MSCs (OMSC-EVs), show more advantages than those of all other MSCs in tissue repair and regeneration, due to their lower invasiveness and easier accessibility for sample collection. Here, we systematically review the biogenesis and biological characteristics of OMSC-EVs, as well as the role of OMSC-EVs in intercellular communication. Furthermore, we discuss the potential therapeutic roles of OMSC-EVs in oral and systemic diseases. We highlight the current challenges and future directions of OMSC-EVs to focus more attention on clinical translation. We aim to provide valuable insights for the explorative clinical application of OMSC-EVs.
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Affiliation(s)
- Huanyu Luo
- Department of Oral Biology, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, School and Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, China
| | - Anahid Ahmadi Birjandi
- Faculty of Dentistry, Oral & Craniofacial Sciences, Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK
| | - Feilong Ren
- Department of Oral Biology, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, School and Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, China
| | - Tianmeng Sun
- Department of Oral Biology, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, School and Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, China
| | - Paul T. Sharpe
- Faculty of Dentistry, Oral & Craniofacial Sciences, Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK
| | - Hongchen Sun
- Department of Oral Pathology, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, School and Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, China
| | - Zhengwen An
- Department of Oral Biology, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, School and Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, China
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9
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Bai X, Cao R, Wu D, Zhang H, Yang F, Wang L. Dental Pulp Stem Cells for Bone Tissue Engineering: A Literature Review. Stem Cells Int 2023; 2023:7357179. [PMID: 37868704 PMCID: PMC10586346 DOI: 10.1155/2023/7357179] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 06/03/2023] [Accepted: 09/19/2023] [Indexed: 10/24/2023] Open
Abstract
Bone tissue engineering (BTE) is a promising approach for repairing and regenerating damaged bone tissue, using stem cells and scaffold structures. Among various stem cell sources, dental pulp stem cells (DPSCs) have emerged as a potential candidate due to their multipotential capabilities, ability to undergo osteogenic differentiation, low immunogenicity, and ease of isolation. This article reviews the biological characteristics of DPSCs, their potential for BTE, and the underlying transcription factors and signaling pathways involved in osteogenic differentiation; it also highlights the application of DPSCs in inducing scaffold tissues for bone regeneration and summarizes animal and clinical studies conducted in this field. This review demonstrates the potential of DPSC-based BTE for effective bone repair and regeneration, with implications for clinical translation.
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Affiliation(s)
- Xiaolei Bai
- Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Ruijue Cao
- Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Danni Wu
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Huicong Zhang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Fan Yang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Linhong Wang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
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10
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Dedier M, Magne B, Nivet M, Banzet S, Trouillas M. Anti-inflammatory effect of interleukin-6 highly enriched in secretome of two clinically relevant sources of mesenchymal stromal cells. Front Cell Dev Biol 2023; 11:1244120. [PMID: 37745306 PMCID: PMC10512713 DOI: 10.3389/fcell.2023.1244120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 08/28/2023] [Indexed: 09/26/2023] Open
Abstract
Despite several advances in the field of regenerative medicine, clinical management of extensive skin wounds or burns remains a major therapeutic issue. During the past few years, Mesenchymal Stromal Cells (MSCs) have emerged as a novel therapeutic tool to promote tissue repair through their anti-inflammatory, pro-trophic and pro-remodeling effects. They exert their biological activity mainly via the secretion of soluble bioactive molecules such as cytokines, growth factors, proteins and microRNAs which can be encapsulated within extracellular vesicles (EV). The recent discovery of their high plasticity to external stimuli has fostered the development of new targeted therapies known as priming strategies, to enhance their potential. Our team recently showed that Interleukin-1β (IL-1β)-primed gingival MSCs promote wound healing and epidermal engraftment in vitro, and in vivo through their secreted products that contain extracellular vesicles. In the present work, we investigated whether two common sources of MSCs, gingiva and bone marrow, could respond similarly to IL-1β to favor pro-healing capabilities of their secretome. We showed that both primed-MSC sources, or their related secreted products, are able to reduce inflammation in LPS-challenged human monocytic THP-1 cell line. IL-1β priming enhanced MSC secretion of wound healing-related growth factors, cytokines and miRNAs in both sources. Among them, interleukin 6 was shown to be involved in the anti-inflammatory effect of MSC secreted products. Overall, these results underline the pro-healing properties of both MSC sources and their secretome upon IL-1β priming and their potential to improve the current medical treatment of severe wounds.
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Affiliation(s)
- Marianne Dedier
- French Armed-forces Biomedical Research Institute (IRBA), Clamart, France
- UMR-MD-U1197, Inserm, Villejuif, France
| | - Brice Magne
- French Armed-forces Biomedical Research Institute (IRBA), Clamart, France
- UMR-MD-U1197, Inserm, Villejuif, France
| | - Muriel Nivet
- French Armed-forces Biomedical Research Institute (IRBA), Clamart, France
- UMR-MD-U1197, Inserm, Villejuif, France
| | - Sébastien Banzet
- French Armed-forces Biomedical Research Institute (IRBA), Clamart, France
- UMR-MD-U1197, Inserm, Villejuif, France
| | - Marina Trouillas
- French Armed-forces Biomedical Research Institute (IRBA), Clamart, France
- UMR-MD-U1197, Inserm, Villejuif, France
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11
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Mohd Nor NH, Mansor NI, Mohd Kashim MIA, Mokhtar MH, Mohd Hatta FA. From Teeth to Therapy: A Review of Therapeutic Potential within the Secretome of Stem Cells from Human Exfoliated Deciduous Teeth. Int J Mol Sci 2023; 24:11763. [PMID: 37511524 PMCID: PMC10380442 DOI: 10.3390/ijms241411763] [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: 06/27/2023] [Revised: 07/18/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
Abstract
Stem cells derived from human exfoliated deciduous teeth (SHED) have emerged as an alternative stem cell source for cell therapy and regenerative medicine because they are readily available, pose fewer ethical concerns, and have low immunogenicity and tumourigenicity. SHED offer a number of advantages over other dental stem cells, including a high proliferation rate with the potential to differentiate into multiple developmental lineages. The therapeutic effects of SHED are mediated by multiple mechanisms, including immunomodulation, angiogenesis, neurogenesis, osteogenesis, and adipogenesis. In recent years, there is ample evidence that the mechanism of action of SHED is mainly due to its paracrine action, releasing a wide range of soluble factors such as cytokines, chemokines, and trophic factors (also known as 'secretome') into the local tissue microenvironment to promote tissue survival and recovery. This review provides an overview of the secretome derived from SHED and highlights the bioactive molecules involved in tissue regeneration and their potential applications in regenerative medicine.
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Affiliation(s)
- Nurul Hafizah Mohd Nor
- Institute of Islamic Civilization, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor Darul Ehsan, Malaysia
| | - Nur Izzati Mansor
- Department of Nursing, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Kuala Lumpur, Malaysia
| | - Mohd Izhar Ariff Mohd Kashim
- Institute of Islamic Civilization, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor Darul Ehsan, Malaysia
- Faculty of Islamic Studies, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor Darul Ehsan, Malaysia
| | - Mohd Helmy Mokhtar
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Kuala Lumpur, Malaysia
| | - Farah Ayuni Mohd Hatta
- Institute of Islamic Civilization, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor Darul Ehsan, Malaysia
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12
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Mattei V, Delle Monache S. Dental Pulp Stem Cells (DPSCs) and Tissue Regeneration: Mechanisms Mediated by Direct, Paracrine, or Autocrine Effects. Biomedicines 2023; 11:biomedicines11020386. [PMID: 36830923 PMCID: PMC9953448 DOI: 10.3390/biomedicines11020386] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 01/18/2023] [Indexed: 01/31/2023] Open
Abstract
Among mesenchymal stem cells, dental pulp stem cells (DPSCs) were discovered most recently [...].
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Affiliation(s)
- Vincenzo Mattei
- Biomedicine and Advanced Technologies Rieti Center, Sabina Universitas, 02100 Rieti, Italy
- Correspondence: (V.M.); (S.D.M.)
| | - Simona Delle Monache
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
- Correspondence: (V.M.); (S.D.M.)
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13
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Huang Y, Zhu M, Liu Z, Hu R, Li F, Song Y, Geng Y, Ma W, Song K, Zhang M. Bone marrow mesenchymal stem cells in premature ovarian failure: Mechanisms and prospects. Front Immunol 2022; 13:997808. [PMID: 36389844 PMCID: PMC9646528 DOI: 10.3389/fimmu.2022.997808] [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: 07/19/2022] [Accepted: 10/17/2022] [Indexed: 12/31/2022] Open
Abstract
Premature ovarian failure (POF) is a common female reproductive disorder and characterized by menopause, increased gonadotropin levels and estrogen deficiency before the age of 40 years old. The etiologies and pathogenesis of POF are not fully clear. At present, hormone replacement therapy (HRT) is the main treatment options for POF. It helps to ameliorate perimenopausal symptoms and related health risks, but can't restore ovarian function and fertility fundamentally. With the development of regenerative medicine, bone marrow mesenchymal stem cells (BMSCs) have shown great potential for the recovery of ovarian function and fertility based on the advantages of abundant sources, high capacity for self-renewal and differentiation, low immunogenicity and less ethical considerations. This systematic review aims to summarize the possible therapeutic mechanisms of BMSCs for POF. A detailed search strategy of preclinical studies and clinical trials on BMSCs and POF was performed on PubMed, MEDLINE, Web of Science and Embase database. A total of 21 studies were included in this review. Although the standardization of BMSCs need more explorations, there is no doubt that BMSCs transplantation may represent a prospective therapy for POF. It is hope to provide a theoretical basis for further research and treatment for POF.
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Affiliation(s)
- Yanjing Huang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Mengdi Zhu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhuo Liu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Runan Hu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Fan Li
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yufan Song
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yuli Geng
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wenwen Ma
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Kunkun Song
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China,*Correspondence: Mingmin Zhang, ; Kunkun Song,
| | - Mingmin Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China,*Correspondence: Mingmin Zhang, ; Kunkun Song,
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14
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Ranjbar E, Tavakol Afshari J, KhajaviRad A, Ebrahimzadeh-Bideskan A, Shafieian R. Insights into the protective capacity of human dental pulp stem cells and its secretome in cisplatin-induced nephrotoxicity: effects on oxidative stress and histological changes. J Basic Clin Physiol Pharmacol 2022; 34:349-356. [PMID: 36201655 DOI: 10.1515/jbcpp-2022-0159] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 09/18/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Acute renal injury (AKI) is a major limiting factor for cisplatin administration. Recent evidence suggests the potential contribution of mesenchymal stem cells (MSCs) to rehabilitation from several disorders via both direct and indirect routes. Thus, the present study aimed, for the first time, to explore and compare the reno-protective potential of human dental pulp-derived stem cells (hDPSCs) vs. hDPSC-conditioned medium (hDPSC-CM) in recovery of impaired kidney tissues in a rat animal model of cisplatin-induced AKI. METHODS AKI was induced via cisplatin injection (n=36). One day after, 24 rats were treated with either hDPSCs or hDPSC-CM (n=12). An extra set of rats (n=12) served as sham group. On days 2 or 7 (n=6), rats were humanly sacrificed for further analysis. Renal injury was explored via measuring serum creatinine and BUN. Renal level of oxidative stress was assessed by determining malondialdehyde, and enzymatic activities of superoxide dismutase and catalase. Renal histopathological changes were scored for comparison among different experimental groups. RESULTS A single dose of cisplatin resulted in considerable renal dysfunction and oxidative stress. Treatment with hDPSCs or hDPSC-CM resulted in significantly restored renal function, reduced level of oxidative stress, and improved histopathological manifestations. Furthermore, as compared to hDPSC-CM, administration of hDPSCs led to superior results in AKI-induced animals. CONCLUSIONS The current study described the first comparative evidence of reno-protective potential of hDPSCs and their CM against cisplatin-induced nephrotoxicity in an AKI rat model, proposing them as useful adjunctive therapy in AKI. Yet, future explorations are still needed.
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Affiliation(s)
- Esmail Ranjbar
- Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Jalil Tavakol Afshari
- Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abolfazl KhajaviRad
- Department of Physiology and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Alireza Ebrahimzadeh-Bideskan
- Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reyhaneh Shafieian
- Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Stem Cell and Regenerative Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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15
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Wang Z, Sun Y, Shen R, Tang X, Xu Y, Zhang Y, Liu Y. Global scientific trends on the immunomodulation of mesenchymal stem cells in the 21st century: A bibliometric and visualized analysis. Front Immunol 2022; 13:984984. [PMID: 36090982 PMCID: PMC9449834 DOI: 10.3389/fimmu.2022.984984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 08/05/2022] [Indexed: 11/15/2022] Open
Abstract
Background Since the discovery of the immunomodulatory functions of mesenchymal stem cells (MSCs), their application in immunomodulation has attracted considerable attention, and an increasing number of studies have been conducted worldwide. Our research aimed to investigate the global status and trends in this field. Methods Publications on the immunomodulatory functions of MSCs from 1 January 2000 to 7 March 2022 were retrieved from the Web of Science Core Collection. The data were studied and indexed using the bibliometric methodology. Visualization analysis, co-authorship, co-occurrence analysis, and publication trends in MSC immunomodulation were conducted using the VOSviewer software. Results In total, 4,227 papers were included in the study. The number of publications and research interests has significantly increased globally. China published the highest number of related articles, while the US published articles with the highest number of citations. Stem Cell Research & Therapy had the highest number of publications. Sun Yat-sen University, Shanghai Jiao Tong University, Harvard University, and Seoul National University were the most contributive institutions. Furthermore, the studies were divided into four research hotspots for MSC immunomodulation: MSC immunomodulation in regenerative medicine, the effects and mechanisms of MSC immunomodulation, MSC therapy for immune diseases, and the cell source of MSCs. Conclusion This study indicates that the number of publications on MSC immunomodulation will increase in the future, and MSC immunomodulation mechanisms and clinical applications of MSC immunotherapy should be the next hotspots in this research field.
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Affiliation(s)
- Zhongqing Wang
- Department of Information Center, The First Hospital of China Medical University, Shenyang, China
| | - Yuqiang Sun
- Department of Emergency, The First Hospital of China Medical University, Shenyang, China
| | - Rou Shen
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, China
- Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, China
| | - Xia Tang
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, China
- Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, China
| | - Yingxin Xu
- Department of Information Center, The First Hospital of China Medical University, Shenyang, China
| | - Ye Zhang
- Department of Information Center, The First Hospital of China Medical University, Shenyang, China
| | - Yao Liu
- Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, China
- Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, China
- *Correspondence: Yao Liu,
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16
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Ogata K, Moriyama M, Matsumura-Kawashima M, Kawado T, Yano A, Nakamura S. The Therapeutic Potential of Secreted Factors from Dental Pulp Stem Cells for Various Diseases. Biomedicines 2022; 10:biomedicines10051049. [PMID: 35625786 PMCID: PMC9138802 DOI: 10.3390/biomedicines10051049] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/18/2022] [Accepted: 04/27/2022] [Indexed: 11/16/2022] Open
Abstract
An alternative source of mesenchymal stem cells has recently been discovered: dental pulp stem cells (DPSCs), including deciduous teeth, which can thus comprise potential tools for regenerative medicine. DPSCs derive from the neural crest and are normally implicated in dentin homeostasis. The clinical application of mesenchymal stem cells (MSCs) involving DPSCs contains various limitations, such as high cost, low safety, and cell handling issues, as well as invasive sample collection procedures. Although MSCs implantation offers favorable outcomes on specific diseases, implanted MSCs cannot survive for a long period. It is thus considered that their mediated mechanism of action involves paracrine effects. It has been recently reported that secreted molecules in DPSCs-conditioned media (DPSC-CM) contain various trophic factors and cytokines and that DPSC-CM are effective in models of various diseases. In the current study, we focus on the characteristics of DPSC-CM and their therapeutic potential against various disorders.
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17
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Guo R, Yu J. Multipotency and Immunomodulatory Benefits of Stem Cells From Human Exfoliated Deciduous Teeth. FRONTIERS IN DENTAL MEDICINE 2022. [DOI: 10.3389/fdmed.2022.805875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Stem cells derived from human exfoliated deciduous teeth (SHEDs) are considered a promising cell population for cell-based or cell-free therapy and tissue engineering because of their proliferative, multipotency and immunomodulator. Based on recent studies, we find that SHEDs show the superior ability of nerve regeneration in addition to the potential of osteogenesis, odontogenesis owing to their derivation from the neural crest. Besides, much evidence suggests that SHEDs have a paracrine effect and can function as immunomodulatory regents attributing to their capability of secreting cytokines and extracellular vesicles. Here, we review the characteristic of SHEDs, their multipotency to regenerate damaged tissues, specifically concentrating on bones or nerves, following the paracrine activity or immunomodulatory benefits of their potential for clinical application in regenerative medicine.
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18
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Kang CM, Shin MK, Jeon M, Lee YH, Song JS, Lee JH. Distinctive cytokine profiles of stem cells from human exfoliated deciduous teeth and dental pulp stem cells. J Dent Sci 2022; 17:276-283. [PMID: 35028048 PMCID: PMC8739254 DOI: 10.1016/j.jds.2021.03.019] [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] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/28/2021] [Indexed: 12/14/2022] Open
Abstract
Background/purpose SHED and DPSC have stem cell regenerative potential, but comparative research on their cytokine profile is rare. This study aimed to investigate and compare cytokine profiles secreted from stem cells from human exfoliated deciduous teeth (SHED) and dental pulp stem cells (DPSCs). Materials and methods SHED-conditioned medium (CM) and DPSC-CM were extracted using seven primary and permanent teeth each. Cytokine membrane array was performed for each CM to quantify and compare the secretomes of 120 cytokines. Enzyme-linked immunosorbent assay, immunocytochemistry, and immunohistochemistry analysis were performed to demonstrate cytokine membrane array analysis. Results Significant differences were observed in the expression levels of 68 cytokines–27 and 41 cytokines were 1.3-fold more strongly expressed in SHED-CM and DPSC-CM, respectively. Cytokines involved in immunomodulation, odontogenesis and osteogenesis were more strongly expressed in SHED-CM. Cytokines involved in angiogenesis were detected more strongly in DPSCs-CM. SHED and DPSCs have distinctive cytokine profiles and characteristics in terms of their stem cell regenerative potential. Conclusion These observations suggest that SHED may have a better cytokine profile related to inflammatory, proliferative, osteogenic, and odontogenic potential.
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Affiliation(s)
- Chung-Min Kang
- Department of Pediatric Dentistry, College of Dentistry, Yonsei University, Seoul, Republic of Korea.,Oral Science Research Center, College of Dentistry, Yonsei University, Seoul, Republic of Korea
| | - Min Kyung Shin
- Department of Pediatric Dentistry, College of Dentistry, Yonsei University, Seoul, Republic of Korea
| | - Mijeong Jeon
- Oral Science Research Center, College of Dentistry, Yonsei University, Seoul, Republic of Korea
| | - Yong-Hyuk Lee
- Oral Science Research Center, College of Dentistry, Yonsei University, Seoul, Republic of Korea
| | - Je Seon Song
- Department of Pediatric Dentistry, College of Dentistry, Yonsei University, Seoul, Republic of Korea.,Oral Science Research Center, College of Dentistry, Yonsei University, Seoul, Republic of Korea
| | - Jae-Ho Lee
- Department of Pediatric Dentistry, College of Dentistry, Yonsei University, Seoul, Republic of Korea.,Oral Science Research Center, College of Dentistry, Yonsei University, Seoul, Republic of Korea
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19
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ZHANG D, WU S. Effects of Foxc1 and Oct4 genes regulating BMSCs transplantation on cardiomyocyte apoptosis after acute myocardial infarction in rats. FOOD SCIENCE AND TECHNOLOGY 2022. [DOI: 10.1590/fst.55321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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20
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Liu P, Zhang Y, Ma Y, Tan S, Ren B, Liu S, Dai H, Xu Z. Application of dental pulp stem cells in oral maxillofacial tissue engineering. Int J Med Sci 2022; 19:310-320. [PMID: 35165516 PMCID: PMC8795794 DOI: 10.7150/ijms.68494] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 12/28/2021] [Indexed: 11/17/2022] Open
Abstract
In the maxillofacial area, soft and hard tissue abnormalities are caused by trauma, tumors, infection, and other causes that expose the maxillofacial region to the surface of the human body. Patients' normal physiological function and appearance are interfered with, and their mental health is adversely impacted, reducing their overall life quality. The pursuit of appropriate medical treatments to correct these abnormalities is thus vital. Autologous stem cell regeneration technology mainly focused on tissues has lately emerged as a significant problem in the medical community. Because of the capacity of dental pulp stem cells (DPSCs) to self-renew, the use of DPSCs from the human pulp tissues of deciduous teeth or permanent teeth has gained popularity among scientists as a stem cell-based therapy option. Aside from that, they are simple to extract and have minimal immunogenicity. As a result, bone tissue engineering may be a critical component in treating maxillofacial and periodontal bone abnormalities. DPSCs activity in maxillofacial and periodontal tissue-engineered bone tissue was investigated in this research.
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Affiliation(s)
- Peng Liu
- Hospital of Stomatology, Jilin University, Changchun 130021, China
| | - Yingxin Zhang
- Department of Oral Emergency, Hospital of Stomatology, Jilin University, Changchun 130021, China
| | - Yujie Ma
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun 130021, China
| | - Shuang Tan
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun 130021, China
| | - Bingyi Ren
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun 130021, China
| | - Shitao Liu
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun 130021, China
| | - HuanYan Dai
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun 130021, China
| | - Zhimin Xu
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun 130021, China
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21
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Zhang Q, Yang T, Zhang R, Liang X, Wang G, Tian Y, Xie L, Tian W. Platelet lysate functionalized gelatin methacrylate microspheres for improving angiogenesis in endodontic regeneration. Acta Biomater 2021; 136:441-455. [PMID: 34551330 DOI: 10.1016/j.actbio.2021.09.024] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 09/13/2021] [Accepted: 09/14/2021] [Indexed: 02/06/2023]
Abstract
Rapid angiogenesis is one of the challenges in endodontic regeneration. Recently, tailored polymeric microsphere system that loaded pro-angiogenic growth factors (GFs) is promising in facilitating vascularization in dental pulp regeneration. In addition, the synergistic effect of multiple GFs is considered more beneficial, but combination usage of them is rather complex and costly. Herein, we aimed to incorporate human platelet lysate (PL), a natural-derived pool of multiple GFs, into gelatin methacrylate (GelMA) microsphere system (GP), which was further modified by Laponite (GPL), a nanoclay with efficient drug delivery ability. These hybrid microspheres were successfully fabricated by electrostatic microdroplet technique with suitable size range (180∼380 µm). After incorporation of the PL and Laponite with GelMA, the Young's modulus of the hybrid hydrogel increased up to about 3-fold and the swelling and degradation rate decreased simultaneously. The PL-derived GFs continued to release up to 28 days from both the GP and GPL microspheres, while the latter released relatively more slowly. What's more, the released GFs could effectively induce tubule formation of human umbilical endothelial cells (HUVECs) and also promote human dental pulp stem cells (hDPSCs) migration. Additionally, the PL component in the GelMA microspheres significantly improved the proliferation, spreading, and odontogenic differentiation of the encapsulated hDPSCs. As further verified by the subcutaneous implantation results, both of the GP and GPL groups enhanced microvascular formation and pulp-like tissue regeneration. This work demonstrated that PL-incorporating GelMA microsphere system was a promising functional vehicle for promoting vascularized endodontic regeneration. STATEMENT OF SIGNIFICANCE: Polymeric microsphere system loaded with pro-angiogenic growth factors (GFs) shows great promise for regeneration of vascularized dental pulp. Herein, we prepared a functional GelMA microsphere system incorporated with human platelet lysates (PL) and nanoclay Laponite by the electrostatic microdroplet method. The results demonstrated that the GelMA/PL/Laponite microspheres significantly improved the spreading, proliferation, and odontogenic differentiation of the encapsulated hDPSCs compared with pure GelMA microspheres. Moreover, they also enhanced microvascular formation and pulp-like tissue regeneration in vivo. This hybrid microsphere system has great potential to accelerate microvessel formation in regenerated dental pulp and other tissues.
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22
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Lee HN, Liang C, Liao L, Tian WD. Advances in Research on Stem Cell-Based Pulp Regeneration. Tissue Eng Regen Med 2021; 18:931-940. [PMID: 34536210 DOI: 10.1007/s13770-021-00389-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 07/17/2021] [Accepted: 08/18/2021] [Indexed: 02/05/2023] Open
Abstract
Although root canal therapy is the most common and widely used treatment at clinical presentation, there are still some postoperative complications. As cell biology and tissue engineering techniques advance rapidly, the use of biological therapy to regenerate dental pulp has become a new trend; Relevant literatures in recent five years were searched using key words such as "root canal therapy", "Dental pulp stem cells", "Dental pulp regeneration", and "Cell homing" in PubMed, Web of Science, etc; Dental pulp stem cells (DPSCs) have multi-differentiation potential, self-renewal capability, and high proliferative ability. Stem cell-based dental pulp regeneration has emerged as a new research hot spot in clinical therapy. Recently, dental pulp-like structures have been generated by the transplantation of exogenous DPSCs or the induction of homing of endogenous DPSCs. Studies on DPSCs are important and significant for dental pulp regeneration and dental restoration; In this review, the existing clinical treatment methods, dental pulp regeneration, and DPSC research status are revealed, and their application prospects are discussed. The stem cell-based pulp regeneration exerts promising potential in clinical therapy for pulp regeneration.
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Affiliation(s)
- Hua-Nien Lee
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases and Engineering Research Center of Oral Translational Medicine, Ministry of Education and National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610044, China
| | - Cheng Liang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases and Engineering Research Center of Oral Translational Medicine, Ministry of Education and National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610044, China
| | - Li Liao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases and Engineering Research Center of Oral Translational Medicine, Ministry of Education and National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610044, China.
| | - Wei-Dong Tian
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases and Engineering Research Center of Oral Translational Medicine, Ministry of Education and National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610044, China.
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Wan J, Zhang G, Li X, Qiu X, Ouyang J, Dai J, Min S. Matrix Metalloproteinase 3: A Promoting and Destabilizing Factor in the Pathogenesis of Disease and Cell Differentiation. Front Physiol 2021; 12:663978. [PMID: 34276395 PMCID: PMC8283010 DOI: 10.3389/fphys.2021.663978] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 06/10/2021] [Indexed: 12/16/2022] Open
Abstract
Cells must alter their expression profiles and morphological characteristics but also reshape the extracellular matrix (ECM) to fulfill their functions throughout their lifespan. Matrix metalloproteinase 3 (MMP-3) is a member of the matrix metalloproteinase (MMP) family, which can degrade multiple ECM components. MMP-3 can activate multiple pro-MMPs and thus initiates the MMP-mediated degradation reactions. In this review, we summarized the function of MMP-3 and discussed its effects on biological activities. From this point of view, we emphasized the positive and negative roles of MMP-3 in the pathogenesis of disease and cell differentiation, highlighting that MMP-3 is especially closely involved in the occurrence and development of osteoarthritis. Then, we discussed some pathways that were shown to regulate MMP-3. By writing this review, we hope to provide new topics of interest for researchers and attract more researchers to investigate MMP-3.
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Affiliation(s)
- Jiangtao Wan
- Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Guowei Zhang
- Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Xin Li
- Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Xianshuai Qiu
- Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Jun Ouyang
- Guangdong Provincial Key Laboratory of Medical Biomechanics, Department of Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Jingxing Dai
- Guangdong Provincial Key Laboratory of Medical Biomechanics, Department of Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Shaoxiong Min
- Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
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24
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Chen P, Wu B, Ji L, Zhan Y, Li F, Cheng L, Cao J, Chen H, Ke Y, Min Z, Sun L, Hua F, Chen H, Cheng Y. Cytokine Consistency Between Bone Marrow and Peripheral Blood in Patients With Philadelphia-Negative Myeloproliferative Neoplasms. Front Med (Lausanne) 2021; 8:598182. [PMID: 34249954 PMCID: PMC8264196 DOI: 10.3389/fmed.2021.598182] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 04/09/2021] [Indexed: 12/23/2022] Open
Abstract
Background: Inflammation might play a critical role in the pathogenesis and progression of Philadelphia-negative myeloproliferative neoplasms (Ph−MPNs) with elevated inflammatory cytokines in peripheral blood (PB). However, the inflammatory status inside the bone marrow (BM), which is the place of malignancy origin and important microenvironment of neoplasm evolution, has not yet been elucidated. Methods: Inflammatory cytokine profiles in PB and BM of 24 Ph-MPNs patients were measured by a multiplex quantitative inflammation array. Cytokines that correlated between PB and BM were selected and then validated by ELISA in a separate cohort of 52 MPN patients. Furthermore, a panel of cytokines was identified and examined for potential application as non-invasive markers for the diagnosis and prediction of fibrosis progress of MPN subtypes. Results: The levels of G-CSF, I-309, IL-1β, IL-1ra, IL-12p40, IL-15, IL-16, M-CSF, MIG, PDGF-BB, and TIMP-1 in BM supernatants were significantly higher than those in PB (all p < 0.05). Linear correlations between BM and PB levels were found in 13 cytokines, including BLC, Eotaxin-2, I-309, sICAM-1, IL-15, M-CSF, MIP-1α, MIP-1δ, RANTES, TIMP-1, TIMP-2, sTNFRI, and sTNFRII (all R > 0.4 and p < 0.05). Levels of BLC, Eotaxin-2, M-CSF, and TIMP-1 in PB were significantly different from those in health controls (all p < 0.05). In PB, levels of TIMP-1 and Eotaxin-2 in essential thrombocythemia (ET) group were significantly lower than those in groups of prefibrotic primary myelofibrosis (pre-PMF) [TIMP-1: 685.2 (322.2–1,229) ng/ml vs. 1,369 (1,175–1,497) ng/ml, p = 0.0221; Eotaxin-2: 531.4 (317.9–756.6) pg/ml vs. 942.4 (699.3–1,474) pg/ml, p = 0.0393] and primary myelofibrosis (PMF) [TIMP-1: 685.2 (322.2–1229) ng/ml vs. 1,365 (1,115–1,681) ng/ml, p = 0.0043; Eotaxin-2: 531.4 (317.9–756.6) pg/ml vs. 1,010 (818–1,556) pg/ml, p = 0.0030]. The level of TIMP-1 in myelofibrosis (MF) >1 group was significantly higher than that in MF ≤ 1 group. Conclusion: Abnormal inflammatory status is present in MPN, especially in its BM microenvironment. Consistency between PB and BM levels was found in multiple inflammatory cytokines. Circulating cytokine levels of BLC, M-CSF, Eotaxin-2, and TIMP-1 reflected inflammation inside BM niche, suggesting potential diagnostic value for MPN subtypes and prognostic value for fibrosis progression.
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Affiliation(s)
- Pu Chen
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Boting Wu
- Department of Transfusion Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lili Ji
- Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yanxia Zhan
- Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Feng Li
- Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, China
| | - Luya Cheng
- Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jingjing Cao
- Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China.,Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hehui Chen
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yang Ke
- Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhihui Min
- Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lihua Sun
- Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, China
| | - Fanli Hua
- Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, China
| | - Hao Chen
- Department of Thoracic Surgery, Zhongshan Hospital Xuhui Branch, Fudan University, Shanghai, China
| | - Yunfeng Cheng
- Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, China.,Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, China.,Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
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Li PL, Wang YX, Zhao ZD, Li ZL, Liang JW, Wang Q, Yin BF, Hao RC, Han MY, Ding L, Wu CT, Zhu H. Clinical-grade human dental pulp stem cells suppressed the activation of osteoarthritic macrophages and attenuated cartilaginous damage in a rabbit osteoarthritis model. Stem Cell Res Ther 2021; 12:260. [PMID: 33933140 PMCID: PMC8088312 DOI: 10.1186/s13287-021-02353-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 04/23/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Although increasing evidence has demonstrated that human dental pulp stem cells (hDPSCs) are efficacious for the clinical treatment of skeletal disorders, the underlying mechanisms remain incompletely understood. Osteoarthritis (OA) is one of the most common degenerative disorders in joints and is characterized by gradual and irreversible cartilaginous tissue damage. Notably, immune factors were newly identified to be closely related to OA development. In this study, we explored the modulatory effects of clinical-grade hDPSCs on osteoarthritic macrophages and their protective effects on cartilaginous tissues in OA joints. METHODS The cell morphology, immunophenotype, and inflammatory factor expression of osteoarthritic macrophages were explored by phase contrast microscope, transmission electron microscopy, immunostaining, flow cytometry, quantitative polymerase chain reaction, and enzyme linked immunosorbent assay, respectively. Additionally, the factors and signaling pathways that suppressed macrophage activation by hDPSCs were determined by enzyme-linked immunosorbent assay and western-blotting. Furthermore, hDPSCs were administered to a rabbit knee OA model via intra-articular injection. Macrophage activation in vivo and cartilaginous tissue damage were also evaluated by pathological analysis. RESULTS We found that hDPSCs markedly inhibited osteoarthritic macrophage activation in vitro. The cell morphology, immunophenotype, and inflammatory factor expression of osteoarthritic macrophages changed into less inflammatory status in the presence of hDPSCs. Mechanistically, we observed that hDPSC-derived hepatocyte growth factor and transforming growth factor β1 mediated the suppressive effects on osteoarthritic macrophages. Moreover, phosphorylation of MAPK pathway proteins contributed to osteoarthritic macrophage activation, and hDPSCs suppressed their activation by partially inactivating those pathways. Most importantly, injected hDPSCs inhibited macrophage activation in osteochondral tissues in a rabbit knee OA model in vivo. Further histological analysis showed that hDPSCs alleviated cartilaginous damage to knee joints. CONCLUSIONS In summary, our findings reveal a novel function for hDPSCs in suppressing osteoarthritic macrophages and suggest that macrophages are efficient cellular targets of hDPSCs for alleviation of cartilaginous damage in OA. hDPSCs treat OA via an osteoarthritic macrophages-dependent mechanisms. hDPSCs suppress the activation of osteoarthritic macrophages in vitro and in vivo and alleviate cartilaginous lesions in OA models.
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Affiliation(s)
- Pei-Lin Li
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, P. R. China
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, P. R. China
| | - Yu-Xing Wang
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, P. R. China
- The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China
- People's Liberation Army General Hospital, Road Fuxing 28, Beijing, 100853, P. R. China
| | - Zhi-Dong Zhao
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, P. R. China
- People's Liberation Army General Hospital, Road Fuxing 28, Beijing, 100853, P. R. China
| | - Zhi-Ling Li
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, P. R. China
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, P. R. China
| | - Jia-Wu Liang
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, P. R. China
- People's Liberation Army General Hospital, Road Fuxing 28, Beijing, 100853, P. R. China
| | - Qian Wang
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, P. R. China
- People's Liberation Army General Hospital, Road Fuxing 28, Beijing, 100853, P. R. China
| | - Bo-Feng Yin
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, P. R. China
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, P. R. China
| | - Rui-Cong Hao
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, P. R. China
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, P. R. China
- Graduate School of Anhui Medical University, 81 Meishan Road, Shu Shan Qu, Hefei, 230032, Anhui, P. R. China
| | - Meng-Yue Han
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, P. R. China
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, P. R. China
- Graduate School of Anhui Medical University, 81 Meishan Road, Shu Shan Qu, Hefei, 230032, Anhui, P. R. China
| | - Li Ding
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, P. R. China.
- Medical Center of Air Forces, PLA, Road Fucheng 30, Beijing, 100142, P. R. China.
| | - Chu-Tse Wu
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, P. R. China.
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, P. R. China.
| | - Heng Zhu
- Beijing Institute of Radiation Medicine, Road Taiping 27, Beijing, 100850, P. R. China.
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, P. R. China.
- Graduate School of Anhui Medical University, 81 Meishan Road, Shu Shan Qu, Hefei, 230032, Anhui, P. R. China.
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Dental Pulp Stem Cells on Implant Surface: An In Vitro Study. BIOMED RESEARCH INTERNATIONAL 2021; 2021:3582342. [PMID: 33834063 PMCID: PMC8012148 DOI: 10.1155/2021/3582342] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 10/28/2020] [Accepted: 03/14/2021] [Indexed: 02/06/2023]
Abstract
In the field of biology and medicine, one hears often about stem cells and their potential. The dental implant new surfaces, subjected to specific treatments, perform better and allow for quicker healing times and better clinical performance. The purpose of this study is to evaluate from a biological point of view the interaction and cytotoxicity between stem cells derived from dental pulp (DPSCs) and titanium surfaces. Through the creation of complex cells/implant, this study is aimed at analyzing the cytotoxicity of dental implant surfaces (Myth (Maipek Manufacturer Industrial Care, Naples, Italy)) and the adhesion capacity of cells on them and at considering the essential factors for implant healing such as osteoinduction and vasculogenesis. These parameters are pointed out through histology (3D cell culture), immunofluorescence, proliferation assays, scanning electron microscopy, and PCR investigations. The results of the dental implant surface and its interaction with the DPSCs are encouraging, obtaining results increasing the mineralization of the tissues. The knowledge of this type of interaction, highlighting its chemical and biological features, is certainly also an excellent starting point for the development of even more performing surfaces for having better healing in the oral surgical procedures related to dental implant positioning.
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Matsumura-Kawashima M, Ogata K, Moriyama M, Murakami Y, Kawado T, Nakamura S. Secreted factors from dental pulp stem cells improve Sjögren's syndrome via regulatory T cell-mediated immunosuppression. Stem Cell Res Ther 2021; 12:182. [PMID: 33726818 PMCID: PMC7962357 DOI: 10.1186/s13287-021-02236-6] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 02/21/2021] [Indexed: 12/12/2022] Open
Abstract
Background Sjögren’s syndrome (SS) is a chronic autoimmune disease primarily characterized by inflammation in the salivary and lacrimal glands. Activated T cells contribute to disease pathogenesis by producing proinflammatory cytokines, which leads to a positive feedback loop establishment. The study aimed to evaluate the effects of secreted factors derived from dental pulp stem cells (DPSCs) or bone marrow mesenchymal stem cells (BMMSCs) on hyposalivation in SS and to investigate the mechanism involved. Methods Eighty percent confluent stem cells were replenished with serum-free Dulbecco’s modified Eagle’s medium and incubated for 48 h; following which, conditioned media from DPSCs (DPSC-CM) and BMMSCs (BMMSC-CM) were collected. Cytokine array analysis was performed to assess the types of cytokines present in the media. Flow cytometric analysis was performed to evaluate the number of activated T cells cultured in DPSC-CM or BMMSC-CM. Subsequently, DPSC-CM or BMMSC-CM was administered to an SS mouse model. The mice were categorized into the following groups (n = 6 each): non-treatment, Dulbecco’s modified Eagle’s medium (−), BMMSC-CM, and DPSC-CM. Histological analysis of the salivary glands was performed. The gene and protein expression levels of cytokines associated with T helper subsets in the submandibular glands (SMGs) were evaluated. Results DPSC-CM contained more secreted factors with tissue-regenerating mechanisms, such as cell proliferation, anti-inflammatory effects, and immunomodulatory effects. DPSC-CM was more effective in suppressing the activated T cells than other groups in the flow cytometric analysis. The stimulated salivary flow rate increased in SS mice with DPSC-CM compared with that in the other groups. In addition, the number of inflammation sites in SMGs of the mice administered with DPSC-CM was lower than that in the other groups. The expression levels of interleukin (Il)-10 and transforming growth factor-β1 were upregulated in the DPSC-CM group, whereas those of Il-4 and Il-17a were downregulated. The DPSC-CM-administered group presented with a significantly increased percentage of regulatory T (Treg) cells and a significantly decreased percentage of type 17 Th (Th17) cells compared with the other groups. Conclusions These results indicated that DPSC-CM ameliorated SS by promoting Treg cell differentiation and inhibiting Th17 cell differentiation in the mouse spleen. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02236-6.
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Affiliation(s)
- Mayu Matsumura-Kawashima
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kenichi Ogata
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Masafumi Moriyama
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yuka Murakami
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Tatsuya Kawado
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Seiji Nakamura
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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Berbéri A, Fayyad-Kazan M, Ayoub S, Bou Assaf R, Sabbagh J, Ghassibe-Sabbagh M, Badran B. Osteogenic potential of dental and oral derived stem cells in bone tissue engineering among animal models: An update. Tissue Cell 2021; 71:101515. [PMID: 33657504 DOI: 10.1016/j.tice.2021.101515] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 02/21/2021] [Accepted: 02/21/2021] [Indexed: 12/20/2022]
Abstract
Small bone defects can heal spontaneously through the bone modeling process due to their physiological environmental conditions. The bone modeling cycle preserves the reliability of the skeleton through the well-adjusted activities of its fundamental cell. Stem cells are a source of pluripotent cells with a capacity to differentiate into any tissue in the existence of a suitable medium. The concept of bone engineering is based on stem cells that can differentiate into bone cells. Mesenchymal stromal cells have been evaluated in bone tissue engineering due to their capacity to differentiate in osteoblasts. They can be isolated from bone marrow and from several adults oral and dental tissues such as permanent or deciduous teeth dental pulp, periodontal ligament, apical dental papilla, dental follicle precursor cells usually isolated from the follicle surrounding the third molar, gingival tissue, periosteum-derived cells, dental alveolar socket, and maxillary sinus Schneiderian membrane-derived cells. Therefore, a suitable animal model is a crucial step, as preclinical trials, to study the outcomes of mesenchymal cells on the healing of bone defects. We will discuss, through this paper, the use of mesenchymal stem cells obtained from several oral tissues mixed with different types of scaffolds tested in different animal models for bone tissue engineering. We will explore and link the comparisons between human and animal models and emphasized the factors that we need to take into consideration when choosing animals. The pig is considered as the animal of choice when testing large size and multiple defects for bone tissue engineering.
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Affiliation(s)
- Antoine Berbéri
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Lebanese University, Beirut, Lebanon.
| | - Mohammad Fayyad-Kazan
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon; Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath- Beirut, Lebanon.
| | - Sara Ayoub
- Department of Prosthodontics, Faculty of Dentistry, Lebanese University, Beirut, Lebanon.
| | - Rita Bou Assaf
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Lebanese University, Beirut, Lebanon.
| | - Joseph Sabbagh
- Department of Restorative Dentistry and Endodontics, Faculty of Dental Medicine, Lebanese University, Beirut, Lebanon.
| | - Michella Ghassibe-Sabbagh
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon.
| | - Bassam Badran
- Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath- Beirut, Lebanon.
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Ogata K, Matsumura-Kawashima M, Moriyama M, Kawado T, Nakamura S. Dental pulp-derived stem cell-conditioned media attenuates secondary Sjögren's syndrome via suppression of inflammatory cytokines in the submandibular glands. Regen Ther 2021; 16:73-80. [PMID: 33659580 PMCID: PMC7878993 DOI: 10.1016/j.reth.2021.01.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 01/01/2021] [Accepted: 01/16/2021] [Indexed: 12/24/2022] Open
Abstract
Introduction Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease, which affects the exocrine glands. Its primary symptoms are decreased moisture in the mouth and eyes. Therapies are limited to treatment with steroids, which has unpleasant side effects, so new treatments would be beneficial. One possibility might be stem cells, such as bone marrow mesenchymal stem cells (BMMSCs) or dental pulp-derived stem cells (DPSCs); these have been reported to exert immunomodulatory effects on activated lymphoid cells. This study aimed to evaluate the effects of conditioned media from DPSCs (DPSC-CM) or BMMSCs (BMMSC-CM) on salivary functions in SS. Methods Cytokine array analysis was performed to assess the types of cytokines present in the media. DPSC-CM or BMMSC-CM was administered in an SS mouse model. Histological analysis of the salivary glands was performed, and gene expression levels of inflammatory and anti-inflammatory cytokines in the submandibular glands (SMGs) were evaluated. Results DPSC-CM contained more anti-inflammatory factors than BMMSC-CM. The mice that were given DPSC-CM had a lower number of inflammation sites in the SMGs than those in the other experimental groups, and their salivary flow rate increased. The expression levels of interleukin (IL)-10 and transforming growth factor-β1 increased in the DPSC-CM group, while those of Il-4, Il-6, and Il-17a decreased. The mice that received DPSC-CM showed a significantly increased percentage of regulatory T cells and a significantly decreased percentage of type T helper 17 cells compared to other groups. Conclusions These results indicate that DPSC-CM could be an effective therapy for SS-induced hyposalivation, since it decreases the number of inflammatory cytokines and regulates the local inflammatory microenvironment in the SMGs.
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Berbéri A, Sabbagh J, Bou Assaf R, Ghassibe-Sabbagh M, Al-Nemer F, El Majzoub R, Fayyad-Kazan M, Badran B. Comparing the osteogenic potential of schneiderian membrane and dental pulp mesenchymal stem cells: an in vitro study. Cell Tissue Bank 2021; 22:409-417. [PMID: 33386464 DOI: 10.1007/s10561-020-09887-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 12/04/2020] [Indexed: 10/22/2022]
Abstract
Mesenchymal stem cells, being characterized by high self-renewal capacity and multi-lineage differentiation potential, are widely used in regenerative medicine especially for repair of bone defects in patients with poor bone regenerative capacity. In this study, we aimed to compare the osteogenic potential of human maxillary schneiderian sinus membrane (hMSSM)-derived stem cells versus permanent teeth dental pulp stem cells (DPSCs). Both cells types were cultivated in osteogenic and non-osteogenic inductive media. Alkaline phosphatase (ALP) activity assay and quantitative real-time PCR analysis were carried out to assess osteogenic differentiation. We showed that ALP activity and osteoblastic markers transcription levels were more striking in hMSSM-derived stem cells than DPSCs. Our results highlight hMSSM-derived stem cells as a recommended stem cell type for usage during bone tissue regenerative therapy.
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Affiliation(s)
- Antoine Berbéri
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Lebanese University, Rafic Hariri Campus, POBox 5208-116, Beirut, Lebanon.
| | - Joseph Sabbagh
- Department of Restorative Dentistry and Endodontics, Faculty of Dental Medicine, Lebanese University, Beirut, Lebanon
| | - Rita Bou Assaf
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Lebanese University, Rafic Hariri Campus, POBox 5208-116, Beirut, Lebanon
| | - Michella Ghassibe-Sabbagh
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon
| | - Fatima Al-Nemer
- Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath, Beirut, Lebanon
| | - Rania El Majzoub
- School of Pharmacy (Department of Biomedical Sciences), Lebanese International University, Mazraa, 146404, Lebanon
| | - Mohammad Fayyad-Kazan
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon. .,Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath, Beirut, Lebanon.
| | - Bassam Badran
- Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath, Beirut, Lebanon
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