|
1
|
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.
Collapse
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.
| |
Collapse
|
|
2
|
Budi HS, Handajani J, Amir LR, Soekanto SA, Ulfa NM, Wulansari SA, Shen YK, Yamada S. Nanoemulgel Development of Stem Cells from Human Exfoliated Deciduous Teeth-Derived Conditioned Medium as a Novel Nanocarrier Growth Factors. Eur J Dent 2025. [PMID: 40267955 DOI: 10.1055/s-0045-1806963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/25/2025] Open
Abstract
OBJECTIVE We aimed to develop a nanoemulgel of stem cells from human exfoliated deciduous teeth-derived conditioned medium (SHED-CM) for oral wound biotherapy candidate. MATERIALS AND METHODS Deciduous tooth pulp was collected from two patients aged 6 years. The mesenchymal stem cell marker expression was analyzed by immunocytochemistry of CD45, CD90, and CD105. Alizarin red staining was performed to differentiate SHEDs from osteoblasts. The quantitative and quantification of transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) secreted into conditioned media were measured using sodium dodecyl sulfate polyacrylamide gel electrophoresis and enzyme-linked immunosorbent assay. The characteristics of the nanoemulgel of SHED-CM (NESCM) were analyzed in terms of organoleptic properties, pH, and homogeneity. The cytotoxicity of NESCM 1.5% was analyzed in human gingival fibroblast (hGF) cell and osteoblast cell line (MC3T3) by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. STATISTICAL ANALYSIS The results were presented as mean ± standard deviation (X ± SD), and the differences between groups were analyzed using the post hoc Tukey's test at a significance level of p-value < 0.05. RESULTS SHEDs were successfully isolated, which were characterized for positive marker expressions of CD90 and CD105 and negative expression of CD45 as well as their osteogenic commitment. In SHED-CM, TGF-β and VEGF were detected on day 1 of conditioning and afterward. Notably, the growth factor enriched as the duration of conditioning increased. The generated nanoemulgel with SHED-CM was stable and homogeneous, and had limited cytotoxic effects on hGF and MC3T3 cell culture. CONCLUSION SHED-CM containing the growth factors can potentially be used as oral wound biotherapy in the form of nanoemulgel.
Collapse
Affiliation(s)
- Hendrik Setia Budi
- Department of Oral Biology, Dental Pharmacology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
- Cell and Biology Research, Surabaya Science Laboratory, Surabaya, Indonesia
| | - Juni Handajani
- Department of Oral Biology, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Lisa Rinanda Amir
- Department of Oral Biology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Sri Angky Soekanto
- Department of Oral Biology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
| | - Ninik Mas Ulfa
- Department of Pharmaceutica, Pharmacology and Clinical Pharmacy, Surabaya Pharmacy Academy, Surabaya, Indonesia
| | - Silvi Ayu Wulansari
- Department of Pharmaceutica, Pharmacology and Clinical Pharmacy, Surabaya Pharmacy Academy, Surabaya, Indonesia
| | - Yung-Kang Shen
- School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Shuntaro Yamada
- Center of Translational Oral Research, University of Bergen, Bergen, Norway
| |
Collapse
|
|
3
|
Entezami S, Sam MR. The role of mesenchymal stem cells-derived from oral and teeth in regenerative and reconstructive medicine. Tissue Cell 2025; 93:102766. [PMID: 39908767 DOI: 10.1016/j.tice.2025.102766] [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: 12/24/2024] [Revised: 01/25/2025] [Accepted: 01/25/2025] [Indexed: 02/07/2025]
Abstract
Defects and abnormalities of the skull, jaw, and face tissues due to various physiological problems such as speech, chewing, and swallowing disorders, cause illness and psychological effects with creation of significant public health challenges. Both autograft and allograft reconstruction methods, have different limitations, especially in the complete reconstruction of complex tissues such as sensory and periodontal tissues, which cannot be wholly relied on for treatment. Recently, mesenchymal stem cells (MSCs)-derived from oral and teeth have emerged as a promising alternative way in regenerative and reconstructive medicine. These types of stem cells with the high differentiation potential and self-renewal capabilities include dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHEDs), periodontal stem cells (PDLSCs) and gum-derived stem cells (GMSCs). These stem cells can be easily collected from accessible and numerous sources, such as extracted molars and milk teeth, with minimal invasiveness, playing pivotal roles in clinical application. This review explains the applications and therapeutic effects of the above-mentioned MSCs-derived from oral and dental tissues. Each of these stem cells, have unique characteristics and used for the treatment of specific abnormalities and defects. In this article, we aims to elucidate the indispensable and pivotal roles of MSCs-derived from the oral and teeth in addressing intractable and complex challenges in restorative and reconstructive medicine.
Collapse
Affiliation(s)
- Sara Entezami
- Department of orthodontics, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz University, Tabriz, Iran
| | - Mohammad Reza Sam
- Department of Biotechnology, Artemia and Aquaculture Research Institute, Urmia University, Urmia, Iran.
| |
Collapse
|
|
4
|
Chansaenroj J, Kornsuthisopon C, Chansaenroj A, Samaranayake LP, Fan Y, Osathanon T. Potential of Dental Pulp Stem Cell Exosomes: Unveiling miRNA-Driven Regenerative Mechanisms. Int Dent J 2025; 75:415-425. [PMID: 39368923 PMCID: PMC11976581 DOI: 10.1016/j.identj.2024.08.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 08/21/2024] [Accepted: 08/24/2024] [Indexed: 10/07/2024] Open
Abstract
Human dental pulp stem cells (hDPSCs) have emerged as a promising resource in regenerative medicine due to their unique ability to secrete exosomes containing a diverse array of bioactive molecules, particularly microRNAs (miRNAs). These exosomes appear to be essential for stimulating regenerative mechanisms, especially those associated with stem cell pluripotency and tissue repair. However, several challenges such as cargo specificity and delivery efficiency need to be addressed to maximise the therapeutic potential of hDPSC-derived exosomes and miRNA-based therapies. This narrative review explores hDPSCs' potential in regenerative medicine by examining their role in tissue engineering, secretome composition, exosome function, exosomal miRNA in diverse models, and miRNA profiling. Therefore, it is imperative to sustain ongoing research on miRNA to advance clinical applications in the field of regenerative medicine and dentistry. A comprehensive understanding of the specific miRNA composition within hDPSC-derived exosomes is essential to elucidate their mechanistic roles in diverse disease states and to inform the development of innovative therapeutic strategies. These findings hold significant potential for the development of innovative regenerative therapies and emphasises the importance of establishing a strong connection between translational research discoveries and clinical applications. hDPSC-derived exosomes and miRNA-based therapies play a crucial role in immune modulation, regenerative dentistry, and tissue repair.
Collapse
Affiliation(s)
- Jira Chansaenroj
- Center of Excellence for Dental Stem Cell Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Chatvadee Kornsuthisopon
- Center of Excellence for Dental Stem Cell Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand; Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
| | - Ajjima Chansaenroj
- Department of Animal Husbandry, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand
| | - Lakshman P Samaranayake
- Office of Research Affairs, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Yi Fan
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Thanaphum Osathanon
- Center of Excellence for Dental Stem Cell Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand; Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
| |
Collapse
|
|
5
|
Su W, Liao C, Liu X. Angiogenic and neurogenic potential of dental-derived stem cells for functional pulp regeneration: A narrative review. Int Endod J 2025; 58:391-410. [PMID: 39660369 DOI: 10.1111/iej.14180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 10/26/2024] [Accepted: 11/22/2024] [Indexed: 12/12/2024]
Abstract
BACKGROUND Dental pulp tissue engineering is expected to become an ideal treatment for irreversible pulpitis and apical periodontitis. However, angiogenesis and neurogenesis for functional pulp regeneration have not yet met the standard for large-scale clinical application, and need further research. OBJECTIVE This review focused on the potential mechanisms of angiogenesis and neurogenesis in pulp regeneration, including stem cell types, upstream and downstream regulatory molecules and cascade signalling pathways, thereby providing a theoretical basis and inspiring new ideas to improve the effectiveness of dental pulp tissue engineering. METHODS An electronic literature search was carried out using the keywords of 'pulp regeneration', 'stem cell transplantation', 'dental pulp stem cells', 'angiogenesis' and 'neurogenesis'. The resulting literature was screened and reviewed. RESULTS Stem cells used in dental pulp tissue engineering can be classified as dental-derived and non-dental-derived stem cells, amongst which dental pulp stem cells (DPSC) have achieved promising results in animal experiments and clinical trials. Multiple molecules and signalling pathways are involved in the process of DPSC-mediated angiogenic and neurogenetic regeneration. In order to promote angiogenesis and neurogenesis in pulp regeneration, feasible measures include the addition of growth factors, the modulation of transcription factors and signalling pathways, the use of extracellular vesicles and the modification of bioscaffold materials. CONCLUSION Dental pulp tissue engineering has had breakthroughs in preclinical and clinical studies in vivo. Overcoming difficulties in pulpal angiogenesis and neurogenesis, and achieving functional pulp regeneration will lead to a significant impact in endodontics.
Collapse
Affiliation(s)
- Wanting Su
- School of Stomatology, Jinan University, Guangzhou, China
| | - Chufang Liao
- School of Stomatology, Jinan University, Guangzhou, China
- Clinical Research Platform for Interdiscipline of Stomatology, Jinan University, Guangzhou, China
- Hospital of stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Xiangning Liu
- School of Stomatology, Jinan University, Guangzhou, China
- Clinical Research Platform for Interdiscipline of Stomatology, Jinan University, Guangzhou, China
- Hospital of stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| |
Collapse
|
|
6
|
Yun YG, Yeo D, Shin SJ, Shin JS, Lee JH, Kim HW. Polydeoxyribonucleotide enhances the bioactivities of stem cells from human exfoliated deciduous teeth through Akt activation. Biochem Biophys Res Commun 2024; 739:150947. [PMID: 39550860 DOI: 10.1016/j.bbrc.2024.150947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 10/06/2024] [Accepted: 11/02/2024] [Indexed: 11/19/2024]
Abstract
Although numerous approaches have emerged to address the challenges of critical limb ischemia (CLI), their clinical trials have proven elusive. Stem cell therapy has been utilized for CLI; however, its efficacy is limited, resulting in low survival rates in patients. Here, we investigated the impact of polydeoxyribonucleotide (PDRN) on the bioactivities of stem cells derived from human exfoliated deciduous teeth (SHED) against oxidative stress. PDRN treatment increased the proliferation, migration, antioxidant properties, and mitochondrial respiration of SHED. These beneficial effects were regulated by Akt activation. Through a murine hindlimb ischemia model, PDRN treatment demonstrated augmented the survival and proliferation of transplanted SHED at ischemic injury sites, whereas the inhibition of Akt suppressed these effects. Our findings revealed that PDRN promoted the therapeutic potential of SHED via Akt phosphorylation, suggesting PDRN-primed SHED as promising candidates for the development of novel stem cell therapeutics.
Collapse
Affiliation(s)
- Yeo Gyun Yun
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 Four NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea
| | - Donghyeon Yeo
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 Four NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea
| | - Seong-Jin Shin
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea; Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan 31116, Republic of Korea
| | - Ji-Sun Shin
- Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan 31116, Republic of Korea; Department of Pediatric Dentistry, College of Dentistry, Dankook University, Cheonan 31116, Republic of Korea
| | - Jun Hee Lee
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 Four NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea; Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 31116, Republic of Korea.
| | - Hae-Won Kim
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 Four NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea; Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan 31116, Republic of Korea.
| |
Collapse
|
|
7
|
Quigley RM, Kearney M, Kennedy OD, Duncan HF. Tissue engineering approaches for dental pulp regeneration: The development of novel bioactive materials using pharmacological epigenetic inhibitors. Bioact Mater 2024; 40:182-211. [PMID: 38966600 PMCID: PMC11223092 DOI: 10.1016/j.bioactmat.2024.06.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 06/05/2024] [Accepted: 06/06/2024] [Indexed: 07/06/2024] Open
Abstract
The drive for minimally invasive endodontic treatment strategies has shifted focus from technically complex and destructive root canal treatments towards more conservative vital pulp treatment. However, novel approaches to maintaining dental pulp vitality after disease or trauma will require the development of innovative, biologically-driven regenerative medicine strategies. For example, cell-homing and cell-based therapies have recently been developed in vitro and trialled in preclinical models to study dental pulp regeneration. These approaches utilise natural and synthetic scaffolds that can deliver a range of bioactive pharmacological epigenetic modulators (HDACis, DNMTis, and ncRNAs), which are cost-effective and easily applied to stimulate pulp tissue regrowth. Unfortunately, many biological factors hinder the clinical development of regenerative therapies, including a lack of blood supply and poor infection control in the necrotic root canal system. Additional challenges include a need for clinically relevant models and manufacturing challenges such as scalability, cost concerns, and regulatory issues. This review will describe the current state of bioactive-biomaterial/scaffold-based engineering strategies to stimulate dentine-pulp regeneration, explicitly focusing on epigenetic modulators and therapeutic pharmacological inhibition. It will highlight the components of dental pulp regenerative approaches, describe their current limitations, and offer suggestions for the effective translation of novel epigenetic-laden bioactive materials for innovative therapeutics.
Collapse
Affiliation(s)
- Ross M. Quigley
- Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin (TCD), University of Dublin, Lincoln Place, Dublin, Ireland
- Department of Anatomy and Regenerative Medicine, and Tissue Engineering Research Group, Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin, Ireland
| | - Michaela Kearney
- Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin (TCD), University of Dublin, Lincoln Place, Dublin, Ireland
| | - Oran D. Kennedy
- Department of Anatomy and Regenerative Medicine, and Tissue Engineering Research Group, Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin, Ireland
- The Trinity Centre for Biomedical Engineering (TCBE) and the Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland (RCSI) and Trinity College Dublin (TCD), Dublin, Ireland
| | - Henry F. Duncan
- Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin (TCD), University of Dublin, Lincoln Place, Dublin, Ireland
- The Trinity Centre for Biomedical Engineering (TCBE) and the Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland (RCSI) and Trinity College Dublin (TCD), Dublin, Ireland
| |
Collapse
|
|
8
|
Zhang X, Hu F, Li J, Chen L, Mao YF, Li QB, Nie CY, Lin C, Xiao J. IGF-1 inhibits inflammation and accelerates angiogenesis via Ras/PI3K/IKK/NF-κB signaling pathways to promote wound healing. Eur J Pharm Sci 2024; 200:106847. [PMID: 38972611 DOI: 10.1016/j.ejps.2024.106847] [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: 03/12/2024] [Revised: 06/13/2024] [Accepted: 07/04/2024] [Indexed: 07/09/2024]
Abstract
Exogenous insulin-like growth factor-1 (IGF-1) has been reported to promote wound healing through regulation of vascular endothelial cells (VECs). Despite the existing studies of IGF-1 on VEC and its role in angiogenesis, the mechanisms regarding anti-inflammatory and angiogenetic effects of IGF-1 remain unclear. In this study, we investigated the wound-healing process and the related signaling pathway of IGF-1 using an inflammation model induced by IFN-γ. The results demonstrated that IGF-1 can increase cell proliferation, suppress inflammation in VECs, and promote angiogenesis. In vivo studies further confirmed that IGF-1 can reduce inflammation, enhance vascular regeneration, and improve re-epithelialization and collagen deposition in acute wounds. Importantly, the Ras/PI3K/IKK/NF-κB signaling pathways was identified as the mechanisms through which IGF-1 exerts its anti-inflammatory and pro-angiogenic effects. These findings contribute to the understanding of IGF-1's role in wound healing and may have implications for the development of new wound treatment approaches.
Collapse
Affiliation(s)
- Xin Zhang
- School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China; Department of Burn, the First Affiliated Hospital of Wenzhou Medical University, Nan Bai Xiang, Wenzhou, Zhejiang 325000, China
| | - Fei Hu
- School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China
| | - Jie Li
- School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China
| | - Lin Chen
- School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China
| | - Yu-Fei Mao
- School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China
| | - Qiu-Bo Li
- School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China; Department of Burn, the First Affiliated Hospital of Wenzhou Medical University, Nan Bai Xiang, Wenzhou, Zhejiang 325000, China
| | - Chen-Yao Nie
- School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China.
| | - Cai Lin
- School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China; Department of Burn, the First Affiliated Hospital of Wenzhou Medical University, Nan Bai Xiang, Wenzhou, Zhejiang 325000, China.
| | - Jian Xiao
- School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China; Department of Burn, the First Affiliated Hospital of Wenzhou Medical University, Nan Bai Xiang, Wenzhou, Zhejiang 325000, China.
| |
Collapse
|
|
9
|
Kong Q, Wang Y, Jiang N, Wang Y, Wang R, Hu X, Mao J, Shi X. Exosomes as Promising Therapeutic Tools for Regenerative Endodontic Therapy. Biomolecules 2024; 14:330. [PMID: 38540750 PMCID: PMC10967740 DOI: 10.3390/biom14030330] [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: 02/13/2024] [Revised: 03/03/2024] [Accepted: 03/08/2024] [Indexed: 11/06/2024] Open
Abstract
Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not allow for genuine structural regeneration and functional reconstruction of the pulp-dentin complex. In recent years, with the development of tissue engineering and regenerative medicine, research on stem cell-based regenerative endodontic therapy (RET) has achieved satisfactory preliminary results, significantly enhancing its clinical translational prospects. As one of the crucial paracrine effectors, the roles and functions of exosomes in pulp-dentin complex regeneration have gained considerable attention. Due to their advantages of cost-effectiveness, extensive sources, favorable biocompatibility, and high safety, exosomes are considered promising therapeutic tools to promote dental pulp regeneration. Accordingly, in this article, we first focus on the biological properties of exosomes, including their biogenesis, uptake, isolation, and characterization. Then, from the perspectives of cell proliferation, migration, odontogenesis, angiogenesis, and neurogenesis, we aim to reveal the roles and mechanisms of exosomes involved in regenerative endodontics. Lastly, immense efforts are made to illustrate the clinical strategies and influencing factors of exosomes applied in dental pulp regeneration, such as types of parental cells, culture conditions of parent cells, exosome concentrations, and scaffold materials, in an attempt to lay a solid foundation for exploring and facilitating the therapeutic strategy of exosome-based regenerative endodontic procedures.
Collapse
Affiliation(s)
- Qingyue Kong
- Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Q.K.); (Y.W.); (Y.W.); (R.W.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Yujie Wang
- Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Q.K.); (Y.W.); (Y.W.); (R.W.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Nan Jiang
- Central Laboratory, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing 100081, China;
| | - Yifan Wang
- Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Q.K.); (Y.W.); (Y.W.); (R.W.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Rui Wang
- Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Q.K.); (Y.W.); (Y.W.); (R.W.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Xiaohan Hu
- Outpatient Department Office, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;
| | - Jing Mao
- Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Q.K.); (Y.W.); (Y.W.); (R.W.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| | - Xin Shi
- Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Q.K.); (Y.W.); (Y.W.); (R.W.)
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
| |
Collapse
|
|
10
|
Yadav P, Vats R, Bano A, Namdev R, Bhardwaj R. Ameliorative potential of stem cells from human exfoliated deciduous teeth (SHED) in preclinical studies: A meta-analysis. Regen Ther 2023; 24:117-134. [PMID: 37441223 PMCID: PMC10333108 DOI: 10.1016/j.reth.2023.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 05/27/2023] [Accepted: 06/07/2023] [Indexed: 07/15/2023] Open
Abstract
The preclinical and clinical role of mesenchymal stem cells from various adult sources is extensively investigated and established in regenerative medicine. However, the comprehensive exploration of the therapeutic potential of Stem cells from human exfoliated deciduous teeth (SHED) is inadequate. Therefore, we performed a systematic meta-analysis of preclinical animal model studies in several diseases to provide insight into SHED's efficacy and therapeutic potential. Two blinded and independent investigators searched the available online databases and scrutinized the included studies. Meta-analysis was performed to evaluate the pooled effect estimate of intervention of SHED by Review Manager 5.4.1. To investigate the therapeutic efficacy of SHED intervention, we also analyzed the test of heterogeneity (I2), overall effect (Z), sensitivity, and publication bias. Among the 2156 scrutinized studies, 40 were included and evaluated as per inclusion and exclusion criteria. The intervention of SHED and its derivatives in several diseases depicted statistically significant therapeutic effects in periodontitis, pulpitis, spinal cord injury, parkinson's disease, alzheimer's disease, focal cerebral ischemia, peripheral nerve injury, and retinal pigmentosa. SHED also improved levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin in liver fibrosis . In autoimmune diseases also, values were significant. SHED also showed a statistically significant reduction of wound healing area and new bone formation in bone defects. The pooled effect estimates of included preclinical studies demonstrated a statistically significant therapeutic effect of SHED in numerous diseases. Based on our data, it is suggested that the potential of SHED may be implemented in clinical trials after conducting a few more preclinical studies.
Collapse
Affiliation(s)
- Pooja Yadav
- Stem Cell Biology Laboratory, Centre for Medical Biotechnology, Maharshi Dayanand University Rohtak, 124001, India
| | - Ravina Vats
- Stem Cell Biology Laboratory, Centre for Medical Biotechnology, Maharshi Dayanand University Rohtak, 124001, India
| | - Afsareen Bano
- Stem Cell Biology Laboratory, Centre for Medical Biotechnology, Maharshi Dayanand University Rohtak, 124001, India
| | - Ritu Namdev
- Dept. of Pediatric Dentistry, Post Graduate Institute of Dental Sciences, Rohtak, 124001, India
| | - Rashmi Bhardwaj
- Stem Cell Biology Laboratory, Centre for Medical Biotechnology, Maharshi Dayanand University Rohtak, 124001, India
| |
Collapse
|
|
11
|
Bastidas JG, Maurmann N, Scholl JN, Weber AF, Silveira RP, Figueiró F, Stimamiglio MA, Marcon B, Correa A, Pranke P. Secretome of stem cells from human exfoliated deciduous teeth (SHED) and its extracellular vesicles improves keratinocytes migration, viability, and attenuation of H 2 O 2 -induced cytotoxicity. Wound Repair Regen 2023; 31:827-841. [PMID: 38038971 DOI: 10.1111/wrr.13131] [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: 03/21/2023] [Revised: 09/14/2023] [Accepted: 11/10/2023] [Indexed: 12/02/2023]
Abstract
Therapies for wound healing using the secretome and extracellular vesicles (EVs) of mesenchymal stem/stromal cells have been shown to be successful in preclinical studies. This study aimed to characterise the protein content of the secretome from stem cells from human exfoliated deciduous teeth (SHED) and analyse the in vitro effects of SHED-conditioned medium (SHED-CM) and SHED extracellular vesicles (SHED-EVs) on keratinocytes. EVs were isolated and characterised. The keratinocyte viability and migration of cells treated with SHED-EVs and conditioned medium (CM) were evaluated. An HaCaT apoptosis model induced by H2 O2 in vitro was performed with H2 O2 followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and live/dead assays. Finally, the expression of vascular endothelial growth factor (VEGF) in keratinocytes treated with secretome and EVs was evaluated by immunofluorescence staining and confirmed with RT-qPCR. SHED-EVs revealed a cup-shaped morphology with expression of the classical markers for exosomes CD9 and CD63, and a diameter of 181 ± 87 nm. The internalisation of EVs by HaCaT cells was confirmed by fluorescence microscopy. Proteomic analysis identified that SHED-CM is enriched with proteins related to stress response and development, including cytokines (CXCL8, IL-6, CSF1, CCL2) and growth factors (IGF2, MYDGF, PDGF). The results also indicated that 50% CM and 0.4-0.6 μg/mL EVs were similarly efficient for improving keratinocyte viability, migration, and attenuation of H2 O2 -induced cytotoxicity. Additionally, expression of VEGF on keratinocytes increased when treated with SHED secretome and EVs. Furthermore, VEGF gene expression in keratinocytes increased significantly when treated with SHED secretome and EVs. Both SHED-CM and SHED-EVs may therefore be promising therapeutic tools for accelerating re-epithelialization in wound healing.
Collapse
Affiliation(s)
- Juliana Girón Bastidas
- Hematology & Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Post Graduate Program in Biological Sciences: Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Natasha Maurmann
- Hematology & Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Post Graduate Program in Biological Sciences: Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Juliete Nathali Scholl
- Post Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Augusto Ferreira Weber
- Post Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Raíssa Padilha Silveira
- Hematology & Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Fabricio Figueiró
- Post Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Biochemistry Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Marco Augusto Stimamiglio
- Stem Cells Basic Biology Laboratory, Instituto Carlos Chagas, FIOCRUZ/PR, Rua Professor Algacyr Munhoz Mader, Curitiba, Paraná, Brazil
| | - Bruna Marcon
- Stem Cells Basic Biology Laboratory, Instituto Carlos Chagas, FIOCRUZ/PR, Rua Professor Algacyr Munhoz Mader, Curitiba, Paraná, Brazil
| | - Alejandro Correa
- Stem Cells Basic Biology Laboratory, Instituto Carlos Chagas, FIOCRUZ/PR, Rua Professor Algacyr Munhoz Mader, Curitiba, Paraná, Brazil
| | - Patricia Pranke
- Hematology & Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Post Graduate Program in Biological Sciences: Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Stem Cell Research Institute (Instituto de Pesquisa com Células-tronco), Porto Alegre, Rio Grande do Sul, Brazil
| |
Collapse
|
|
12
|
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.
Collapse
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
| |
Collapse
|
|
13
|
Ruan Q, Tan S, Guo L, Ma D, Wen J. Prevascularization techniques for dental pulp regeneration: potential cell sources, intercellular communication and construction strategies. Front Bioeng Biotechnol 2023; 11:1186030. [PMID: 37274160 PMCID: PMC10232868 DOI: 10.3389/fbioe.2023.1186030] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 05/10/2023] [Indexed: 06/06/2023] Open
Abstract
One of the difficulties of pulp regeneration is the rapid vascularization of transplanted engineered tissue, which is crucial for the initial survival of the graft and subsequent pulp regeneration. At present, prevascularization techniques, as emerging techniques in the field of pulp regeneration, has been proposed to solve this challenge and have broad application prospects. In these techniques, endothelial cells and pericytes are cocultured to induce intercellular communication, and the cell coculture is then introduced into the customized artificial vascular bed or induced to self-assembly to simulate the interaction between cells and extracellular matrix, which would result in construction of a prevascularization system, preformation of a functional capillary network, and rapid reconstruction of a sufficient blood supply in engineered tissue after transplantation. However, prevascularization techniques for pulp regeneration remain in their infancy, and there remain unresolved problems regarding cell sources, intercellular communication and the construction of prevascularization systems. This review focuses on the recent advances in the application of prevascularization techniques for pulp regeneration, considers dental stem cells as a potential cell source of endothelial cells and pericytes, discusses strategies for their directional differentiation, sketches the mechanism of intercellular communication and the potential application of communication mediators, and summarizes construction strategies for prevascularized systems. We also provide novel ideas for the extensive application and follow-up development of prevascularization techniques for dental pulp regeneration.
Collapse
Affiliation(s)
| | | | | | - Dandan Ma
- *Correspondence: Dandan Ma, ; Jun Wen,
| | - Jun Wen
- *Correspondence: Dandan Ma, ; Jun Wen,
| |
Collapse
|
|
14
|
Song WP, Jin LY, Zhu MD, Wang H, Xia DS. Clinical trials using dental stem cells: 2022 update. World J Stem Cells 2023; 15:31-51. [PMID: 37007456 PMCID: PMC10052340 DOI: 10.4252/wjsc.v15.i3.31] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/20/2023] [Accepted: 03/08/2023] [Indexed: 03/23/2023] Open
Abstract
For nearly 20 years, dental stem cells (DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth and exfoliated deciduous teeth, periodontal ligaments, dental follicles, and gingival and apical papilla. They have several properties (such as self-renewal, multidirectional differentiation, and immunomodulation) and exhibit enormous potential for clinical applications. To date, many clinical articles and clinical trials using DSCs have reported the treatment of pulpitis, periapical lesions, periodontitis, cleft lip and palate, acute ischemic stroke, and so on, and DSC-based therapies obtained satisfactory effects in most clinical trials. In these studies, no adverse events were reported, which suggested the safety of DSC-based therapy. In this review, we outline the characteristics of DSCs and summarize clinical trials and their safety as DSC-based therapies. Meanwhile, we also present the current limitations and perspectives of DSC-based therapy (such as harvesting DSCs from inflamed tissue, applying DSC-conditioned medium/DSC-derived extracellular vesicles, and expanding-free strategies) to provide a theoretical basis for their clinical applications.
Collapse
Affiliation(s)
- Wen-Peng Song
- Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Lu-Yuan Jin
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
| | - Meng-Di Zhu
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
| | - Hao Wang
- Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Deng-Sheng Xia
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China.
| |
Collapse
|
|
15
|
Tian Y, Lin J, Li X, Zhu G, Fan L, Lou S, Li D, Pan Y. Mechanical dissection and culture of mouse cranial neural crest cells. Birth Defects Res 2023; 115:417-429. [PMID: 36621938 DOI: 10.1002/bdr2.2148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 12/21/2022] [Accepted: 12/22/2022] [Indexed: 01/10/2023]
Abstract
Owing to the contribution of cranial neural crest cells (CNCCs) to the majority of craniofacial structures, they have been studied extensively for the pathogenesis of craniofacial diseases. To investigate and summarize how to isolate and culture the CNCCs from wild-type mice, a literature search was performed in online databases (PubMed and Web of Science) using optimized keywords "mouse," "cranial neural crest cell" and "culture." The literature was checked by two investigators according to the screening and exclusion criteria. Initially, 197 studies were retrieved from PubMed and 169 from Web of Science, and after excluding replicate studies, 293 articles were considered. Finally, 17 studies met all the criteria and were included in this review. The results showed that obtaining purified stem cells and balancing the need to promote cell growth and prevent unwanted early cell differentiation were the two key points in the isolation and culture of CNCCs. However, no standard criteria are available for answering these questions. Thus, it is important to emphasize the necessity for standardization of CNCC isolation, culture, and identification in research on craniofacial diseases.
Collapse
Affiliation(s)
- Yu Tian
- Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, Jiangsu Province, China.,Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Junyan Lin
- Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, Jiangsu Province, China.,Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Xiaofeng Li
- Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, Jiangsu Province, China.,Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Guirong Zhu
- Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, Jiangsu Province, China.,Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Liwen Fan
- Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, Jiangsu Province, China.,Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.,Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, Jiangsu Province, China
| | - Shu Lou
- Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, Jiangsu Province, China.,Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.,Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, Jiangsu Province, China
| | - Dandan Li
- Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, Jiangsu Province, China.,Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.,Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, Jiangsu Province, China
| | - Yongchu Pan
- Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, Jiangsu Province, China.,Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.,Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, Jiangsu Province, China
| |
Collapse
|
|
16
|
Birjandi AA, Sharpe P. Potential of extracellular space for tissue regeneration in dentistry. Front Physiol 2022; 13:1034603. [DOI: 10.3389/fphys.2022.1034603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 10/24/2022] [Indexed: 11/19/2022] Open
Abstract
With the proven relationship between oral and general health and the growing aging population, it is pivotal to provide accessible therapeutic approaches to regenerate oral tissues and restore clinical function. However, despite sharing many core concepts with medicine, dentistry has fallen behind the progress in precision medicine and regenerative treatments. Stem cell therapies are a promising avenue for tissue regeneration, however, ethical, safety and cost issues may limit their clinical use. With the significance of paracrine signalling in stem cell and tissue regeneration, extracellular space comprising of the cell secretome, and the extracellular matrix can serve as a potent source for tissue regeneration. Extravesicles are secreted and naturally occurring vesicles with biologically active cargo that can be harvested from the extracellular space. These vesicles have shown great potential as disease biomarkers and can be used in regenerative medicine. As a cell free therapy, secretome and extracellular vesicles can be stored and transferred easily and pose less ethical and safety risks in clinical application. Since there are currently many reviews on the secretome and the biogenesis, characterization and function of extracellular vesicles, here we look at the therapeutic potential of extracellular space to drive oral tissue regeneration and the current state of the field in comparison to regenerative medicine.
Collapse
|
|
17
|
de Oliveira NK, Ferraz EP, Rosin FCP, Correa L, Deboni MCZ. Poly-ε-caprolactone/poly(rotaxane) seeded with human dental pulp stem cells or osteoblasts promotes angiogenesis: a chorioallantoic membrane assay. JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2022; 33:2051-2066. [PMID: 35719115 DOI: 10.1080/09205063.2022.2091372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 06/14/2022] [Accepted: 06/15/2022] [Indexed: 06/15/2023]
Abstract
Biomaterials used for tissue regeneration should ideally provide a favorable environment for cell proliferation and differentiation. Angiogenesis is crucial for supplying oxygen and nutrients necessary for cellular survival at implantation sites. The aim of this study was to evaluate the overall angiogenesis response of a poly ε-caprolactone/poly (rotaxane) blend (poly-blend) carried by human dental pulp stem cells (hDPSCs) or osteoblasts (OB) seeded in the chorioallantoic membranes (CAM) of fertilized chicken eggs on embryonic day 7. They were classified into the following intervention groups: (a) poly(polymeric blend disks free of cells); (b) hDPSC seeded onto CAM; (c) poly/hDPSC (where hDPSCs were seeded onto poly-blend); (d) poly/OB (where osteoblasts were seeded onto poly); (e) OB (where hDPSCs differentiated into osteoblasts were seeded onto CAM); and (f) a negative control when a sterilized silicone ring free of cells or polymer was inserted into CAM. On embryonic day 14, the quantitative and qualitative characteristics of the blood vessels in the CAMs were analyzed macroscopically and microscopically. Macroscopic examination showed that the Poly/hDPSC samples exhibited an increased medium vessel density. Additionally, microscopic observations showed that the Poly/hDPSC group and poly alone resulted in a large lumen area of vascularization. Thus, poly ε-caprolactone/poly (rotaxane) did not impair angiogenesis. Furthermore, poly-blend carried by stem cells of dental pulp origin shows a better vasculogenic potential, which is essential for regenerative therapies.
Collapse
Affiliation(s)
| | - Emanuela Prado Ferraz
- Oral Surgery Department, School of Dentistry, University of São Paulo - FOUSP, São Paulo, SP, Brazil
| | | | - Luciana Correa
- Pathology Department, School of Dentistry, University of São Paulo - FOUSP, São Paulo, SP, Brazil
| | | |
Collapse
|
|
18
|
Vu HT, Yoon JY, Park JH, Lee HH, Dashnyam K, Kim HW, Lee JH, Shin JS, Kim JB. The Potential Application of Human Gingival Fibroblast-Conditioned Media in Pulp Regeneration: An In Vitro Study. Cells 2022; 11:3398. [PMID: 36359794 PMCID: PMC9657428 DOI: 10.3390/cells11213398] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/21/2022] [Accepted: 10/25/2022] [Indexed: 08/27/2023] Open
Abstract
Regenerative endodontic treatment based on tissue engineering has recently gained interest in contemporary restorative dentistry. However, low survival rates and poor potential differentiation of stem cells could undermine the success rate of pulp regenerative therapy. Human gingival fibroblast-conditioned medium (hGF-CM) has been considered a potential therapy for tissue regeneration due to its stability in maintaining multiple factors essential for tissue regeneration compared to live cell transplantation. This study aimed to investigate the potency of hGF-CM on stem cells from human dental pulp (DPSC) in pulp regeneration. A series of experiments confirmed that hGF-CM contributes to a significant increase in proliferation, migration capability, and cell viability of DPSC after H2O2 exposure. Moreover, it has been proved to facilitate the odontogenic differentiation of DPSC via qRT-PCR, ALP (alkaline phosphatase), and ARS (Alizarin Red S) staining. It has been discovered that such highly upregulated odontogenesis is related to certain types of ECM proteins (collagen and laminin) from hGF-CM via proteomics. In addition, it is found that the ERK pathway is a key mechanism via inhibition assay based on RNA-seq result. These findings demonstrate that hGF-CM could be beneficial biomolecules for pulp regeneration.
Collapse
Affiliation(s)
- Huong Thu Vu
- Department of Pediatric Dentistry, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
| | - Ji-Young Yoon
- Cell & Matter Institute, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
| | - Jae-Hee Park
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
- Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
| | - Hae-Hyoung Lee
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
- Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
- Department of Biomaterials science, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
- UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
| | - Khandmaa Dashnyam
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
- Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
- Drug Research Institute, Mongolian University of Pharmaceutical Science, Ulaanbaatar 976, Mongolia
| | - Hae-Won Kim
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
- Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
- UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
- Mechanobiology Dental Medicine Research Centre, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
| | - Jung-Hwan Lee
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
- Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
- UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
- Mechanobiology Dental Medicine Research Centre, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
| | - Ji-Sun Shin
- Department of Pediatric Dentistry, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
| | - Jong-Bin Kim
- Department of Pediatric Dentistry, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea
| |
Collapse
|
|
19
|
Dieterle MP, Gross T, Steinberg T, Tomakidi P, Becker K, Vach K, Kremer K, Proksch S. Characterization of a Stemness-Optimized Purification Method for Human Dental-Pulp Stem Cells: An Approach to Standardization. Cells 2022; 11:cells11203204. [PMID: 36291072 PMCID: PMC9600643 DOI: 10.3390/cells11203204] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/06/2022] [Accepted: 10/09/2022] [Indexed: 11/16/2022] Open
Abstract
Human dental pulp stem cells (hDPSCs) are promising for oral/craniofacial regeneration, but their purification and characterization is not yet standardized. hDPSCs from three donors were purified by magnetic activated cell sorting (MACS)-assisted STRO-1-positive cell enrichment (+), colony derivation (c), or a combination of both (c/+). Immunophenotype, clonogenicity, stemness marker expression, senescence, and proliferation were analyzed. Multilineage differentiation was assessed by qPCR, immunohistochemistry, and extracellular matrix mineralization. To confirm the credibility of the results, repeated measures analysis and post hoc p-value adjustment were applied. All hDPSC fractions expressed STRO-1 and were similar for several surface markers, while their clonogenicity and expression of CD10/44/105/146, and 166 varied with the purification method. (+) cells proliferated significantly faster than (c/+), while (c) showed the highest increase in metabolic activity. Colony formation was most efficient in (+) cells, which also exhibited the lowest cellular senescence. All hDPSCs produced mineralized extracellular matrix. Regarding osteogenic induction, (c/+) revealed a significant increase in mRNA expression of COL5A1 and COL6A1, while osteogenic marker genes were detected at varying levels. (c/+) were the only population missing BDNF gene transcription increase during neurogenic induction. All hDPSCs were able to differentiate into chondrocytes. In summary, the three hDPSCs populations showed differences in phenotype, stemness, proliferation, and differentiation capacity. The data suggest that STRO-1-positive cell enrichment is the optimal choice for hDPSCs purification to maintain hDPSCs stemness. Furthermore, an (immuno) phenotypic characterization is the minimum requirement for quality control in hDPSCs studies.
Collapse
Affiliation(s)
- Martin Philipp Dieterle
- Division of Oral Biotechnology, Center for Dental Medicine, Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany
| | - Tara Gross
- Department of Operative Dentistry and Periodontology, Centre for Dental Medicine Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79106 Freiburg, Germany
- G.E.R.N. Center for Tissue Replacement, Regeneration & Neogenesis, Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79108 Freiburg, Germany
| | - Thorsten Steinberg
- Division of Oral Biotechnology, Center for Dental Medicine, Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany
- Correspondence: ; Tel.: +49-761-27047460
| | - Pascal Tomakidi
- Division of Oral Biotechnology, Center for Dental Medicine, Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany
| | - Kathrin Becker
- Department of Operative Dentistry and Periodontology, Centre for Dental Medicine Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79106 Freiburg, Germany
| | - Kirstin Vach
- Institute of Medical Biometry and Statistics, Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany
| | - Katrin Kremer
- Department of Oral and Maxillofacial Surgery, Center for Dental Medicine, Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79106 Freiburg, Germany
| | - Susanne Proksch
- Department of Operative Dentistry and Periodontology, Centre for Dental Medicine Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79106 Freiburg, Germany
- G.E.R.N. Center for Tissue Replacement, Regeneration & Neogenesis, Medical Center—University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, 79108 Freiburg, Germany
| |
Collapse
|
|
20
|
Sugiaman VK, Djuanda R, Pranata N, Naliani S, Demolsky WL. Tissue Engineering with Stem Cell from Human Exfoliated Deciduous Teeth (SHED) and Collagen Matrix, Regulated by Growth Factor in Regenerating the Dental Pulp. Polymers (Basel) 2022; 14:polym14183712. [PMID: 36145860 PMCID: PMC9503223 DOI: 10.3390/polym14183712] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 08/25/2022] [Accepted: 09/02/2022] [Indexed: 11/16/2022] Open
Abstract
Maintaining dental pulp vitality and preventing tooth loss are two challenges in endodontic treatment. A tooth lacking a viable pulp loses its defense mechanism and regenerative ability, making it more vulnerable to severe damage and eventually necessitating extraction. The tissue engineering approach has drawn attention as an alternative therapy as it can regenerate dentin-pulp complex structures and functions. Stem cells or progenitor cells, extracellular matrix, and signaling molecules are triad components of this approach. Stem cells from human exfoliated deciduous teeth (SHED) are a promising, noninvasive source of stem cells for tissue regeneration. Not only can SHEDs regenerate dentin-pulp tissues (comprised of fibroblasts, odontoblasts, endothelial cells, and nerve cells), but SHEDs also possess immunomodulatory and immunosuppressive properties. The collagen matrix is a material of choice to provide structural and microenvironmental support for SHED-to-dentin pulp tissue differentiation. Growth factors regulate cell proliferation, migration, and differentiation into specific phenotypes via signal-transduction pathways. This review provides current concepts and applications of the tissue engineering approach, especially SHEDs, in endodontic treatment.
Collapse
Affiliation(s)
- Vinna K Sugiaman
- Department of Oral Biology, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Rudy Djuanda
- Department of Conservative Dentistry and Endodontic, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Natallia Pranata
- Department of Oral Biology, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Silvia Naliani
- Department of Prosthodontics, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Wayan L Demolsky
- Department of Oral Biology, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| |
Collapse
|
|
21
|
Noohi P, Abdekhodaie MJ, Nekoofar MH, Galler KM, Dummer PMH. Advances in Scaffolds Used for Pulp-Dentine Complex Tissue Engineering - A Narrative Review. Int Endod J 2022; 55:1277-1316. [PMID: 36039729 DOI: 10.1111/iej.13826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 07/28/2022] [Accepted: 08/10/2022] [Indexed: 11/27/2022]
Abstract
Pulp necrosis in immature teeth disrupts root development and predisposes roots to fracture as a consequence of their thin walls and open apices. Regenerative endodontics is a developing treatment modality whereby necrotic pulps are replaced with newly formed healthy tissue inside the root canal. Many clinical studies have demonstrated the potential of this strategy to stimulate root maturation and apical root-end closure. However, clinical outcomes are patient-dependent and unpredictable. The development of predictable clinical protocols is achieved through the interplay of the three classical elements of tissue engineering, namely, stem cells, signaling molecules, and scaffolds. Scaffolds provide structural support for cells to adhere and proliferate and also regulate cell differentiation and metabolism. Hence, designing and fabricating an appropriate scaffold is a crucial step in tissue engineering. In this review, four main classes of scaffolds used to engineer pulp-dentine complexes, including bioceramic-based scaffolds, synthetic polymer-based scaffolds, natural polymer-based scaffolds, and composite scaffolds, are covered. Additionally, recent advances in the design, fabrication, and application of such scaffolds are analysed along with their advantages and limitations. Finally, the importance of vascular network establishment in the success of pulp-dentine complex regeneration and strategies used to create scaffolds to address this challenge are discussed.
Collapse
Affiliation(s)
- Parisa Noohi
- Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran
| | - Mohammad J Abdekhodaie
- Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran
| | - Mohammad H Nekoofar
- Department of Endodontics, School of Dentistry, Tehran University of Medical Sciences Tehran University of Medical Sciences, Tehran, Iran.,Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Department of Endodontic, Bahçeşehir University School of Dentistry, Istanbul, Turkey
| | - Kerstin M Galler
- Department of Conservative Dentistry and Periodontology, University Hospital Erlangen-Nürnberg, Erlangen, Germany
| | - Paul M H Dummer
- School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
| |
Collapse
|
|
22
|
Badodekar N, Mishra S, Telang G, Chougule S, Bennur D, Thakur M, Vyas N. Angiogenic Potential and Its Modifying Interventions in Dental Pulp Stem Cells: a Systematic Review. REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE 2022. [DOI: 10.1007/s40883-022-00270-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
|
|
23
|
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.
Collapse
|
|
24
|
Chouaib B, Cuisinier F, Collart-Dutilleul PY. Dental stem cell-conditioned medium for tissue regeneration: Optimization of production and storage. World J Stem Cells 2022; 14:287-302. [PMID: 35662860 PMCID: PMC9136565 DOI: 10.4252/wjsc.v14.i4.287] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 05/19/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSC) effects on tissue regeneration are mainly mediated by their secreted substances (secretome), inducing their paracrine activity. This Conditioned medium (CM), including soluble factors (proteins, nucleic acids, lipids) and extracellular vesicles is emerging as a potential alternative to cell therapy. However, the manufacturing of CM suffers from variable procedures and protocols leading to varying results between studies. Besides, there is no well-defined optimized procedure targeting specific applications in regenerative medicine. AIM To focus on conditioned medium produced from dental MSC (DMSC-CM), we reviewed the current parameters and manufacturing protocols, in order to propose a standardization and optimization of these manufacturing procedures. METHODS We have selected all publications investigating the effects of dental MSC secretome in in vitro and in vivo models of tissue regeneration, in accordance with the PRISMA guidelines. RESULTS A total of 351 results were identified. And based on the inclusion criteria described above, 118 unique articles were included in the systematic review. DMSC-CM production was considered at three stages: before CM recovery (cell sources for CM), during CM production (culture conditions) and after production (CM treatment). CONCLUSION No clear consensus could be recovered as evidence-based methods, but we were able to describe the most commonly used protocols: donors under 30 years of age, dental pulp stem cells and exfoliated deciduous tooth stem cells with cell passage between 1 and 5, at a confluence of 70% to 80%. CM were often collected during 48 h, and stored at -80 °C. It is important to point out that the preconditioning environment had a significant impact on DMSC-CM content and efficiency.
Collapse
Affiliation(s)
- Batoul Chouaib
- Laboratory Bioengineering and Nanosciences UR_UM104, University of Montpellier, Montpellier 34000, France
| | - Frédéric Cuisinier
- Laboratory Bioengineering and Nanosciences UR_UM104, University of Montpellier, Montpellier 34000, France
| | | |
Collapse
|
|
25
|
Su J, Ge X, Jiang N, Zhang Z, Wu X. Efficacy of Mesenchymal Stem Cells from Human Exfoliated DeciduousTeeth and their Derivatives in Inflammatory Diseases Therapy. Curr Stem Cell Res Ther 2022; 17:302-316. [PMID: 35440314 DOI: 10.2174/1574888x17666220417153309] [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: 12/28/2021] [Revised: 02/01/2022] [Accepted: 02/28/2022] [Indexed: 11/22/2022]
Abstract
Mesenchymal stem cells derived from postnatal orofacial tissues can be readily isolated and possess diverse origins, for example, from surgically removed teeth or gingiva. These cells exhibit stem cell properties, strong potential for self-renewal, and show multi-lineage differentiation, and they have therefore been widely employed in stem cell therapy, tissue regeneration, and inflammatory diseases. Among them, stem cells from human exfoliated deciduous teeth [SHED] and their derivatives have manifested wide application in the treatment of diseases because of their outstanding advantages- including convenient access, easy storage, and less immune rejection. Numerous studies have shown that most diseases are closely associated with inflammation and that inflammatory diseases are extremely destructive, can lead to necrosis of organ parenchymal cells, and can deposit excessive extracellular ma- trix in the tissues. Inflammatory diseases are thus the principal causes of disability and death from many diseases worldwide. SHED and their derivatives not only exhibit the basic characteristics of stem cells but also exhibit some special properties of their own, particularly with regard to their great potential in inhib- iting inflammation and tissue regeneration. SHED therapy may provide a new direction for the treatment of inflammation and corresponding tissue defects. In this review, we critically analyze and summarize the latest findings on the behaviors and functions of SHED, serum‑free conditioned medium from SHED [SHED-CM], and extracellular vesicles, especially exosomes, from SHED [SHED-Exos], and discuss their roles and underlying mechanisms in the control of inflammatory diseases, thus further highlighting additional functions for SHED and their derivatives in future therapies.
Collapse
Affiliation(s)
| | - Xuejun Ge
- Shanxi Medical University School and Hospital of Stomatology & Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan 030001, China
| | | | - Ziqian Zhang
- Shanxi Medical University School and Hospital of Stomatology & Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan 030001, China
| | - Xiaowen Wu
- Shanxi Medical University School and Hospital of Stomatology & Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan 030001, China
| |
Collapse
|
|
26
|
Vu HT, Han MR, Lee JH, Kim JS, Shin JS, Yoon JY, Park JH, Dashnyam K, Knowles JC, Lee HH, Kim JB, Lee JH. Investigating the Effects of Conditioned Media from Stem Cells of Human Exfoliated Deciduous Teeth on Dental Pulp Stem Cells. Biomedicines 2022; 10:biomedicines10040906. [PMID: 35453661 PMCID: PMC9027398 DOI: 10.3390/biomedicines10040906] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 04/07/2022] [Accepted: 04/08/2022] [Indexed: 12/24/2022] Open
Abstract
Pulp regeneration has recently attracted interest in modern dentistry. However, the success ratio of pulp regeneration is low due to the compromising potential of stem cells, such as their survival, migration, and odontoblastic differentiation. Stem cells from human exfoliated deciduous teeth (SHED) have been considered a promising tool for regenerative therapy due to their ability to secrete multiple factors that are essential for tissue regeneration, which is achieved by minimally invasive procedures with fewer ethical or legal concerns than those of other procedures. The aim of this study is to investigate the potency of SHED-derived conditioned media (SHED CM) on dental pulp stem cells (DPSCs), a major type of mesenchymal stem cells for dental pulp regeneration. Our results show the promotive efficiency of SHED CM on the proliferation, survival rate, and migration of DPSCs in a dose-dependent manner. Upregulation of odontoblast/osteogenic-related marker genes, such as ALP, DSPP, DMP1, OCN, and RUNX2, and enhanced mineral deposition of impaired DPSCs are also observed in the presence of SHED CM. The analysis of SHED CM found that a variety of cytokines and growth factors have positive effects on cell proliferation, migration, anti-apoptosis, and odontoblast/osteogenic differentiation. These findings suggest that SHED CM could provide some benefits to DPSCs in pulp regeneration.
Collapse
Affiliation(s)
- Huong Thu Vu
- Department of Pediatric Dentistry, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea; (H.T.V.); (M.-R.H.); (J.-H.L.); (J.-S.K.); (J.-S.S.)
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Korea; (J.-Y.Y.); (J.-H.P.); (K.D.); (J.C.K.); (H.-H.L.)
| | - Mi-Ran Han
- Department of Pediatric Dentistry, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea; (H.T.V.); (M.-R.H.); (J.-H.L.); (J.-S.K.); (J.-S.S.)
| | - Jun-Haeng Lee
- Department of Pediatric Dentistry, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea; (H.T.V.); (M.-R.H.); (J.-H.L.); (J.-S.K.); (J.-S.S.)
| | - Jong-Soo Kim
- Department of Pediatric Dentistry, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea; (H.T.V.); (M.-R.H.); (J.-H.L.); (J.-S.K.); (J.-S.S.)
| | - Ji-Sun Shin
- Department of Pediatric Dentistry, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea; (H.T.V.); (M.-R.H.); (J.-H.L.); (J.-S.K.); (J.-S.S.)
| | - Ji-Young Yoon
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Korea; (J.-Y.Y.); (J.-H.P.); (K.D.); (J.C.K.); (H.-H.L.)
- Department of Biomaterials science, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea
| | - Jeong-Hui Park
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Korea; (J.-Y.Y.); (J.-H.P.); (K.D.); (J.C.K.); (H.-H.L.)
- Department of Biomaterials science, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea
| | - Khandmaa Dashnyam
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Korea; (J.-Y.Y.); (J.-H.P.); (K.D.); (J.C.K.); (H.-H.L.)
- Department of Biomaterials science, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea
- Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea
| | - Jonathan Campbell Knowles
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Korea; (J.-Y.Y.); (J.-H.P.); (K.D.); (J.C.K.); (H.-H.L.)
- Department of Biomaterials science, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea
- UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea
- Mechanobiology Dental Medicine Research Centre, Cheonan 31116, Korea
- Cell & Matter Institue, Dankook University, Cheonan 31116, Korea
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK
| | - Hae-Hyoung Lee
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Korea; (J.-Y.Y.); (J.-H.P.); (K.D.); (J.C.K.); (H.-H.L.)
- UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea
- The Discoveries Centre for Regenerative and Precision Medicine, Eastman Dental Institute, University College, London WC1E 6BT, UK
| | - Jong-Bin Kim
- Department of Pediatric Dentistry, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea; (H.T.V.); (M.-R.H.); (J.-H.L.); (J.-S.K.); (J.-S.S.)
- Correspondence: (J.-B.K.); (J.-H.L.); Tel.: +82-41-550-3081 (J.-B.K. & J.-H.L.); Fax: +82-41-559-7839 (J.-B.K. & J.-H.L.)
| | - Jung-Hwan Lee
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Korea; (J.-Y.Y.); (J.-H.P.); (K.D.); (J.C.K.); (H.-H.L.)
- Department of Biomaterials science, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea
- UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, 119 Dandae-ro, Cheonan 31116, Korea
- Mechanobiology Dental Medicine Research Centre, Cheonan 31116, Korea
- The Discoveries Centre for Regenerative and Precision Medicine, Eastman Dental Institute, University College, London WC1E 6BT, UK
- Drug Research Institute, Mongolian Pharmaceutical University & Monos Group, Ulaanbaatar 14250, Mongolia
- Correspondence: (J.-B.K.); (J.-H.L.); Tel.: +82-41-550-3081 (J.-B.K. & J.-H.L.); Fax: +82-41-559-7839 (J.-B.K. & J.-H.L.)
| |
Collapse
|
|
27
|
Carvalho GL, Sarra G, Schröter GT, Silva LSRG, Ariga SKK, Gonçalves F, Caballero-Flores HV, Moreira MS. Pro-angiogenic potential of a functionalized hydrogel scaffold as a secretome delivery platform: An innovative strategy for cell homing-based dental pulp tissue engineering. J Tissue Eng Regen Med 2022; 16:472-483. [PMID: 35244346 DOI: 10.1002/term.3294] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 02/01/2022] [Accepted: 02/17/2022] [Indexed: 01/03/2023]
Abstract
Angiogenesis is a key process that provides a suitable environment for successful tissue engineering and is even more crucial in regenerative endodontic procedures, since the root canal anatomy limits the development of a vascular network supply. Thus, sustainable and accelerated vascularization of tissue-engineered dental pulp constructs remains a major challenge in cell homing approaches. This study aimed to functionalize a chitosan hydrogel scaffold (CS) as a platform loaded with secretomes of stem cells from human exfoliated deciduous teeth (SHEDs) and evaluate its bioactive function and pro-angiogenic properties. Initially, the CS was loaded with SHED secretomes (CS-S), and the release kinetics of several trophic factors were assessed. Proliferation and chemotaxis assays were performed to analyze the effect of functionalized scaffold on stem cells from apical papilla (SCAPs) and the angiogenic potential was analyzed through the Matrigel tube formation assay with co-cultured of human umbilical vein endothelial cells and SCAPs. SHEDs and SCAPs expressed typical levels of mesenchymal stem cell surface markers. CS-S was able to release the trophic factors in a sustained manner, but each factor has its own release kinetics. The CS-S group showed a significantly higher proliferation rate, accelerated the chemotaxis, and higher capacity to form vascular-like structures. CS-S provided a sustained and controlled release of trophic factors, which, in turn, improved proliferation, chemotaxis and all angiogenesis parameters in the co-culture. Thus, the functionalization of chitosan scaffolds loaded with secretomes is a promising platform for cell homing-based tissue engineering.
Collapse
Affiliation(s)
- Giovanna Lopes Carvalho
- Post-Graduation Program in Dentistry, School of Dentistry, Ibirapuera University, São Paulo, Brazil
| | - Giovanna Sarra
- Department of Restorative Dentistry, School of Dentistry, University of São Paulo, São Paulo, Brazil
| | | | | | - Suely Kunimi Kubo Ariga
- Department of Clinical Medicine, School of Medicine, Emergency Medicine Laboratory, University of São Paulo, São Paulo, Brazil
| | - Flávia Gonçalves
- Post-Graduation Program in Dentistry, School of Dentistry, Ibirapuera University, São Paulo, Brazil
| | | | - Maria Stella Moreira
- Post-Graduation Program in Dentistry, School of Dentistry, Ibirapuera University, São Paulo, Brazil.,Department of Stomatology, A.C. Camargo Cancer Center, São Paulo, Brazil
| |
Collapse
|
|
28
|
Sarra G, Machado MEDL, Caballero-Flores HV, Moreira MS, Pedroni ACF, Marques MM. Effect of human dental pulp stem cell conditioned medium in the dentin-pulp complex regeneration: A pilot in vivo study. Tissue Cell 2021; 72:101536. [PMID: 33932880 DOI: 10.1016/j.tice.2021.101536] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 03/19/2021] [Accepted: 03/22/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Dental trauma, restorative operative procedures and/or caries lesions can expose the dental pulp. Facing this clinical condition, where the maintenance of the dentin-pulp complex vitality is imperative, is challenging in Dentistry. Dental pulp stem cells conditioned medium contains trophic factors that could help in this task. This in vivo pilot study aimed to evaluate the effects of the human dental pulp stem cells conditioned medium on the dental pulp tissue response to vital pulp therapy. MATERIAL AND METHODS Concentrated conditioned medium was obtained by incubating characterized human dental pulp stem cells with fresh culture medium. Pulp exposures performed at the first upper molars (n = 20) of Wistar rats were directly capped with: MTA or MTA + Conditioned Medium. Four and 8 weeks later, the samples were qualitatively analyzed in histological sections (H&E). RESULTS When the conditioned medium was associated with MTA, there were a high percentage of samples presenting formation of dentin bridges and small percentage of pulp tissue with inflammatory signs in both experimental times. The conditioned medium improved the organization of the newly formed hard tissue. CONCLUSIONS The association of dental pulp stem cell conditioned medium with MTA showed beneficial effects on dentin-pulp complex regeneration and has promising potential for studies in regenerative dentistry.
Collapse
Affiliation(s)
- Giovanna Sarra
- Department of Restorative Dentistry, School of Dentistry, University of Sao Paulo (USP), Sao Paulo, SP, Brazil
| | | | | | | | - Ana Clara Fagundes Pedroni
- Department of Restorative Dentistry, School of Dentistry, University of Sao Paulo (USP), Sao Paulo, SP, Brazil; Post Graduation Program, Ibirapuera University (UNIB), Sao Paulo, SP, Brazil
| | | |
Collapse
|
|
29
|
Bousnaki M, Bakopoulou A, Pich A, Papachristou E, Kritis A, Koidis P. Mapping the Secretome of Dental Pulp Stem Cells Under Variable Microenvironmental Conditions. Stem Cell Rev Rep 2021; 18:1372-1407. [PMID: 34553309 DOI: 10.1007/s12015-021-10255-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/27/2021] [Indexed: 12/31/2022]
Abstract
There is substantial evidence supporting the anti-inflammatory and regenerative potential of dental pulp stem cells (DPSCs) through direct cell transplantation or paracrine action. However, DPSC secretome profile remains inadequately studied. This study provides proteomic profiling of the human DPSC secretome by comparatively analysising cell lysates and respective culture supernatants (i.e. conditioned media-CM) under variable oxygen tension conditions (normoxia-20% O2/CM_Norm vs. hypoxia 2% O2/CM_Hyp) and/or stimulation with Tumor Necrosis Factor alpha (TNF-α). DPSC-CM samples and respective crude lysates (DPSC-CL) were collected and subjected to SDS-PAGE, followed by LC-MS/MS analysis. The identified proteins were analyzed by Gene Ontology, Reactome, and String databases. The anti-inflammatory properties of DPSC-CMs were validated via an in vitro RAW_246.7 murine macrophages model through evaluation of the expression of pro-and anti-inflammatory markers by real-time PCR. Results showed a total of 2413 proteins identified in CM_Norm, 2479 in CM_Norm+TNF-α, 1642 in CM_Hyp, and 2002 in CM_Hyp + TNF-α samples. CM_Norm contained 122 proteins statistically significantly upregulated compared to the CM_Hyp and involved in pathways related to "ECM organization", "cellular response to hypoxia", and "IL signaling". Functional network analysis showed that TGFβ1, TIMP1 and TIMP2 were key nodes among proteins significantly upregulated in the CM_Norm compared to the CM_Hyp, interacting with more than 10 proteins, each. DPSC-CM application in the in vitro RAW_246.7 model decreased the expression of pro-inflammatory markers (MMP-3, MMP-9, MMP-13, MCP-1), while increasing anti-inflammatory markers (IL-10). Overall, DPSC-CM collected under normoxic conditions is enriched with anti-inflammatory, tissue repair and regenerative factors, which prompts further investigation on its therapeutic applications.
Collapse
Affiliation(s)
- M Bousnaki
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences (FHS), Aristotle University of Thessaloniki (AUTh), GR-54124, Thessaloniki, Greece
| | - A Bakopoulou
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences (FHS), Aristotle University of Thessaloniki (AUTh), GR-54124, Thessaloniki, Greece.
| | - A Pich
- Research Core Unit Proteomics & Institute of Toxicology, Hannover Medical School, 30625, Hannover, Germany
| | - E Papachristou
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences (FHS), Aristotle University of Thessaloniki (AUTh), GR-54124, Thessaloniki, Greece
| | - A Kritis
- Department of Physiology and Pharmacology, School of Medicine, Faculty of Health Sciences (FHS), Aristotle University of Thessaloniki (AUTh), Thessaloniki, Greece
| | - P Koidis
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences (FHS), Aristotle University of Thessaloniki (AUTh), GR-54124, Thessaloniki, Greece.
| |
Collapse
|
|
30
|
Shoushrah SH, Transfeld JL, Tonk CH, Büchner D, Witzleben S, Sieber MA, Schulze M, Tobiasch E. Sinking Our Teeth in Getting Dental Stem Cells to Clinics for Bone Regeneration. Int J Mol Sci 2021; 22:6387. [PMID: 34203719 PMCID: PMC8232184 DOI: 10.3390/ijms22126387] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/27/2021] [Accepted: 06/02/2021] [Indexed: 12/12/2022] Open
Abstract
Dental stem cells have been isolated from the medical waste of various dental tissues. They have been characterized by numerous markers, which are evaluated herein and differentiated into multiple cell types. They can also be used to generate cell lines and iPSCs for long-term in vitro research. Methods for utilizing these stem cells including cellular systems such as organoids or cell sheets, cell-free systems such as exosomes, and scaffold-based approaches with and without drug release concepts are reported in this review and presented with new pictures for clarification. These in vitro applications can be deployed in disease modeling and subsequent pharmaceutical research and also pave the way for tissue regeneration. The main focus herein is on the potential of dental stem cells for hard tissue regeneration, especially bone, by evaluating their potential for osteogenesis and angiogenesis, and the regulation of these two processes by growth factors and environmental stimulators. Current in vitro and in vivo publications show numerous benefits of using dental stem cells for research purposes and hard tissue regeneration. However, only a few clinical trials currently exist. The goal of this review is to pinpoint this imbalance and encourage scientists to pick up this research and proceed one step further to translation.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Edda Tobiasch
- Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig- Strasse. 20, 53359 Rheinbach, Germany; (S.H.S.); (J.L.T.); (C.H.T.); (D.B.); (S.W.); (M.A.S.); (M.S.)
| |
Collapse
|
|
31
|
Mattei V, Martellucci S, Pulcini F, Santilli F, Sorice M, Delle Monache S. Regenerative Potential of DPSCs and Revascularization: Direct, Paracrine or Autocrine Effect? Stem Cell Rev Rep 2021; 17:1635-1646. [PMID: 33829353 PMCID: PMC8553678 DOI: 10.1007/s12015-021-10162-6] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/23/2021] [Indexed: 12/13/2022]
Abstract
A new source of mesenchymal stem cells has recently been discovered, the so-called dental pulp derived stem cells (DPSCs) which therefore could represent potentially tools for regenerative medicine. DPSC originate from the neural crest and are physiologically involved in dentin homeostasis; moreover, they contribute to bone remodeling and differentiation into several tissues including cartilage, bone, adipose and nervous tissues. DPSCs have also been shown to influence the angiogenesis process, for example through the release of secretory factors or by differentiating into vascular and/or perivascular cells. Angiogenesis, that has a pivotal role in tissue regeneration and repair, is defined as the formation of new vessels from preexisting vessels and is mediated by mutual and reciprocal interactions between endothelial cells and perivascular cells. It is also known that co-cultures of perivascular and endothelial cells (ECs) can form a vascular network in vitro and also in vivo. Since DPSCs seem to have characteristics similar to pericytes, understanding the possible mechanism of interaction between DPSCs and ECs during neo-angiogenesis is dramatically important for the development of advanced clinical application in the field of regeneration.
Collapse
Affiliation(s)
- Vincenzo Mattei
- Biomedicine and Advanced Technologies Rieti Center, Sabina Universitas, 02100, Rieti, Italy
- Department of Experimental Medicine, "Sapienza" University, 00161, Rome, Italy
| | - Stefano Martellucci
- Biomedicine and Advanced Technologies Rieti Center, Sabina Universitas, 02100, Rieti, Italy
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100, L'Aquila, Italy
| | - Fanny Pulcini
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100, L'Aquila, Italy
| | - Francesca Santilli
- Biomedicine and Advanced Technologies Rieti Center, Sabina Universitas, 02100, Rieti, Italy
- Department of Experimental Medicine, "Sapienza" University, 00161, Rome, Italy
| | - Maurizio Sorice
- Department of Experimental Medicine, "Sapienza" University, 00161, Rome, Italy
| | - Simona Delle Monache
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100, L'Aquila, Italy.
- StemTeCh Group, Chieti, Italy.
| |
Collapse
|
|
32
|
Chin YT, Liu CM, Chen TY, Chung YY, Lin CY, Hsiung CN, Jan YS, Chiu HC, Fu E, Lee SY. 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside-stimulated dental pulp stem cells-derived conditioned medium enhances cell activity and anti-inflammation. J Dent Sci 2020; 16:586-598. [PMID: 33854707 PMCID: PMC8025232 DOI: 10.1016/j.jds.2020.10.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 10/29/2020] [Indexed: 02/07/2023] Open
Abstract
Background/purpose Dental pulp stem cells (DPSCs) contribute to the regeneration of various tissues and have superior proliferation, immune privilege, and anti-inflammation properties to other mesenchymal stem cells. 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) not only enhances the aforementioned properties of DPSCs but also promotes self-renewal and reprogramming-like ability. However, whether THSG enhances the aforementioned properties and abilities through direct or indirect interaction mechanisms remains unclear. To address this knowledge gap, we examined the effects of THSG-stimulated DPSC-derived conditioned medium (THSG-CM) on the activity and anti-inflammation properties of cells. Materials and methods DPSCs were treated with various concentrations of THSG to produce THSG-CM, which was then collected, analyzed, and lyophilized. A cytokine profiling antibody assay was used to compare protein components between THSG-treated and nontreated CM. Human skin fibroblasts (HSFs) and human gingival fibroblasts (HGFs) were used to investigate the effect of THSG-CM on cell proliferation, anti-inflammation, and wound healing abilities; for this investigation, MTS assay, quantitative real-time PCR analysis, and 2-well silicone inserts wound model were conducted. Results We observed that THSG enhanced the secretion of growth- and immune-associated proteins in THSG-CM and increased the proliferation of HSFs and HGFs. Furthermore, THSG-CM significantly attenuated lipopolysaccharide-stimulated mRNA levels of cytokines in both cells and improved wound healing abilities. Conclusion We conclude that THSG-CM had more beneficial effects on cell activity and anti-inflammation in the HSFs and HGFs than DPSC-derived CM. DPSC-derived CM can be developed into a cell-free regenerative strategy in the future, and its therapeutic efficacy may be improved by THSG-CM.
Collapse
Affiliation(s)
- Yu-Tang Chin
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.,Center for Tooth Bank and Dental Stem Cell Technology, Taipei Medical University, Taipei, Taiwan
| | - Che-Ming Liu
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.,Department of Dentistry, Wan-Fang Medical Center, Taipei Medical University, Taipei, Taiwan
| | - Ting-Yi Chen
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.,Department of Dentistry, Wan-Fang Medical Center, Taipei Medical University, Taipei, Taiwan
| | - Yao-Yu Chung
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chi-Yu Lin
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.,Center for Tooth Bank and Dental Stem Cell Technology, Taipei Medical University, Taipei, Taiwan
| | - Chao-Nan Hsiung
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yun-Shen Jan
- Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Hsien-Chung Chiu
- Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan
| | - Earl Fu
- Department of Dentistry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Xindian, New Taipei City, Taiwan
| | - Sheng-Yang Lee
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.,Center for Tooth Bank and Dental Stem Cell Technology, Taipei Medical University, Taipei, Taiwan.,Department of Dentistry, Wan-Fang Medical Center, Taipei Medical University, Taipei, Taiwan
| |
Collapse
|
|
33
|
Potential Therapeutic Effects of Exosomes in Regenerative Endodontics. Arch Oral Biol 2020; 120:104946. [PMID: 33129129 DOI: 10.1016/j.archoralbio.2020.104946] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 09/07/2020] [Accepted: 10/04/2020] [Indexed: 02/05/2023]
Abstract
OBJECTIVE This review aims to describe the basic characteristics of exosomes, and summarize their possible source and potential biological effects in pulp regeneration, providing new insights into the therapeutic role of exosomes for regenerative endodontics in the future. DESIGN A comprehensive review of scientific literature related to exosomes potentially used for pulp regeneration was conducted. RESULTS Dental mesenchymal stem cells (MSCs) play an important role in dental pulp regeneration. MSC-derived exosomes, as important biotransmitters in intercellular communication, have been shown to replicate the therapeutic effects of their parental cells. These exosomes have better stability, lower immunogenicity, higher safety and clinical efficiency, making it possible to apply them in pulp regeneration. Existing research suggests that exosomes could trigger the regeneration of dentin/pulp-like tissue in vivo, which may attribute to their role in promoting pulp angiogenesis, regulating dental cell proliferation, migration and differentiation, and providing neuroprotection. CONCLUSIONS The applications of exosomes in the treatment of pulp regeneration have great potential, and exosomes may become ideal therapeutic biomaterial in regenerative endodontics.
Collapse
|
|
34
|
Duan S, Zhang Y, Yuan F, Jiang A, Sang Y, Huang G. Corneal endothelial expansion using human umbilical cord mesenchymal stem cell-derived conditioned medium. J Cell Physiol 2020; 236:2606-2615. [PMID: 32853402 DOI: 10.1002/jcp.30014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 08/02/2020] [Accepted: 08/05/2020] [Indexed: 12/13/2022]
Abstract
Rabbit corneal endothelial cells are frequently used in pharmacological experiments and are useful for corneal transplant experiments. We performed the present study to analyze the effect of conditioned medium (CM) derived from human umbilical cord mesenchymal stem cells (HUMSCs) on the growth of rabbit corneal endothelial cells (RCECs) and to establish a program for expansion of RCECs in vitro. RCECs were cultured using a CM derived from HUMSCs (HUMSCs-CM) in vitro. The proliferation ability of RCECs cultured in the presence of HUMSCs-CM was evaluated by conducting 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, colony formation, and scratch migration assays. The proliferation ability of RCECs maintained in HUMSCs-CM was significantly enhanced as compared to RCECs cultivated in the control group. Immunofluorescence indicated that zonula occludens-1 (ZO-1) and N-cadherin were located at intercellular junctions. Real-time PCR and western blot analyses demonstrated that the CEC-relative functional markers were expressed in RCECs maintained in HUMSCs-CM. Flow cytometry analyses demonstrated that HUMSCs-CM promoted the G0/G1 entrance to the S phase in RCECs. Our results demonstrated that HUMSCs-CM induced the proliferation of RCECs in vitro and maintained the necessary characteristic phenotypes. The expanded RCECs may provide a promising cell source for experimental research and clinical therapy.
Collapse
Affiliation(s)
- Sujuan Duan
- Department of Ophthalmology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.,Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yanyan Zhang
- Medical Department of Graduate School, Nanchang University, Nanchang, Jiangxi, China
| | - Fangxiu Yuan
- Department of Ophthalmology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Alan Jiang
- Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yi Sang
- Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Guofu Huang
- Department of Ophthalmology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.,Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| |
Collapse
|
|
35
|
Rosaian AS, Rao GN, Mohan SP, Vijayarajan M, Prabhakaran RC, Sherwood A. Regenerative Capacity of Dental Pulp Stem Cells: A Systematic Review. JOURNAL OF PHARMACY AND BIOALLIED SCIENCES 2020; 12:S27-S36. [PMID: 33149427 PMCID: PMC7595477 DOI: 10.4103/jpbs.jpbs_121_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 03/06/2020] [Accepted: 03/13/2020] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVES The dental pulp contains undifferentiated mesenchymal cells, blood vessels and so on, which are responsible for routine functions of a tooth. The determination of stemness and regenerative properties using biomarkers and further application in routine practice may unravel its potential. MATERIALS AND METHODS Inclusion criteria-original research articles published in English, from 2000 to 2019, were collected both manually and by electronic search from databases of Cochrane, Medline, Embase, and PubMed. Exclusion criteria-articles other than English and review manuscripts were omitted. The shortlisted articles were reviewed for specific biomarkers, to assess the regenerative potential, stemness, and lineage of dental pulp stem cells. RESULTS Of 512 articles, 64 were selected and reviewed to determine the mesenchymal, neurogenic, vasculogenic, hematopoietic, and stem cell potential. On the basis of the search analysis, a panel of markers was proposed. CONCLUSION The application of proposed markers, on a pulpectomized tissue derived from human teeth, may be helpful to determine the regenerative potential and the usefulness in regenerative medicine and tissue engineering.
Collapse
Affiliation(s)
- Adlin S Rosaian
- Department of Oral and Maxillofacial Pathology and Oral Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
| | - Gururaj Narayana Rao
- Department of Oral and Maxillofacial Pathology and Oral Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
| | - Sunil P Mohan
- Department of Oral Pathology, Sree Anjaneya Institute of Dental Sciences, Kozhikode, Kerala, India
- Department of Stem Cells and Regenerative Medicine, Sree Anjaneya Institute of Dental Sciences, Kozhikode, Kerala, India
| | - Mahalakshmi Vijayarajan
- Department of Oral and Maxillofacial Pathology and Oral Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
| | - Rebekkah C Prabhakaran
- Department of Oral and Maxillofacial Pathology and Oral Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
| | - Anand Sherwood
- Department of Operative Dentistry and Endodontics, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
| |
Collapse
|
|
36
|
Xu M, Wang J, Zhang X, Yan T, Wu B, Bi K, Jia Y. Polysaccharide from Schisandra chinensis acts via LRP-1 to reverse microglia activation through suppression of the NF-κB and MAPK signaling. JOURNAL OF ETHNOPHARMACOLOGY 2020; 256:112798. [PMID: 32251761 DOI: 10.1016/j.jep.2020.112798] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 03/18/2020] [Accepted: 03/24/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Schisandra chinensis (Turcz.) Baill (S. Chinensis), a traditional Chinese medicine frequently used in the traditional treatment of dementia, its polysaccharide component has been widely reported. AIM OF THE STUDY In this paper, we studied whether SCP2-1, a natural product of homogeneous polysaccharide from S. Chinensis, could improve M1 and M2 polarization and inhibit neuroinflammation through lipoprotein receptor-related protein-1 (LRP-1), and futher exerted anti-inflammatory and neuroprotective effects. MATERIALS AND METHODS SCP2-1 was obtained from crude polysaccharide of S. Chinensis, BV2 microglia cells and mice stimulated by LPS were served to detect the positive role of SCP2-1 in M1/M2 polarization. The concentration of cytokine expression, IL-1β, TNF-α, IL-12 and IL-6 for M1 polarization and TGF-β, IL-10, IL-4 and Arg-1 for M2 polarization, in the BV2 and hippocampus were tested by ELISA kits. CD86 and CD206, as surface markers of M1 and M2, were tested by flow cytometry. We examined the expression of LRP-1 in BV2 cells and mouse hippocampus. The addition of siRNA for LRP-1 demonstrated the important role of LRP-1 in the neuroprotection of SCP2-1. Western blot was used to detect the activation of various mitogen-activated protein kinase (MAPKs) pathway, i.e. the phosphorylation of JNK and ERK proteins, and nuclear translocation of nuclear factor κB (NF-κB). H.E. staining was used to observe Histopathological changes. RESULTS SCP2-1 could reverse M1/M2 polarization in vitro culture and suppressed M1 polarization in the hippocampus of mice stimulated with LPS. After LPS stimulation, poor levels of LRP-1, hyperactivation of the JNK and NF-κB was appeared, which could improve by SCP2-1. The addition of siRNA for LRP-1 suppressed the protection of SCP2-1 in BV2 microglial cells. More importantly, SCP2-1 could improve LPS-induced cognitive dysfunction in mice in Y-maze and NOR test. CONCLUSIONS SCP2-1 could improve M1/M2 polarization, especially inhibit M1 polarization, and ameliorate the cognition of mice in Y-maze and NOR test. SCP2-1 play a neuroprotective role through LRP-1 to reverse activation of microglia via suppressing the overactive NF-κB and JNK pathway.
Collapse
Affiliation(s)
- Mengjie Xu
- Key Laboratory of Active Components of Chinese Medicine Screening and Evaluation, School of Traditional Chinese MateriaMedica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China
| | - Jinyu Wang
- Key Laboratory of Active Components of Chinese Medicine Screening and Evaluation, School of Traditional Chinese MateriaMedica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China
| | - Xiaoying Zhang
- Key Laboratory of Active Components of Chinese Medicine Screening and Evaluation, School of Traditional Chinese MateriaMedica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China
| | - Tingxu Yan
- Key Laboratory of Active Components of Chinese Medicine Screening and Evaluation, School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China
| | - Bo Wu
- Key Laboratory of Active Components of Chinese Medicine Screening and Evaluation, School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China
| | - Kaishun Bi
- The Engineering Laboratory of National and Local Union of Quality Control for Traditional Chinese Medicine, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China
| | - Ying Jia
- Key Laboratory of Active Components of Chinese Medicine Screening and Evaluation, School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China.
| |
Collapse
|
|
37
|
Therapeutic Functions of Stem Cells from Oral Cavity: An Update. Int J Mol Sci 2020; 21:ijms21124389. [PMID: 32575639 PMCID: PMC7352407 DOI: 10.3390/ijms21124389] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 06/14/2020] [Accepted: 06/17/2020] [Indexed: 12/11/2022] Open
Abstract
Adult stem cells have been developed as therapeutics for tissue regeneration and immune regulation due to their self-renewing, differentiating, and paracrine functions. Recently, a variety of adult stem cells from the oral cavity have been discovered, and these dental stem cells mostly exhibit the characteristics of mesenchymal stem cells (MSCs). Dental MSCs can be applied for the replacement of dental and oral tissues against various tissue-damaging conditions including dental caries, periodontitis, and oral cancers, as well as for systemic regulation of excessive inflammation in immune disorders, such as autoimmune diseases and hypersensitivity. Therefore, in this review, we summarized and updated the types of dental stem cells and their functions to exert therapeutic efficacy against diseases.
Collapse
|
|
38
|
Yusof MFH, Hashim SNM, Zahari W, Chandra H, Noordin KBAA, Kannan TP, Hamid SSA, Mokhtar KI, Azlina A. Amniotic Membrane Enhance the Effect of Vascular Endothelial Growth Factor on the Angiogenic Marker Expression of Stem Cells from Human Exfoliated Deciduous Teeth. Appl Biochem Biotechnol 2020; 191:177-190. [PMID: 32096060 DOI: 10.1007/s12010-020-03266-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 02/13/2020] [Indexed: 12/11/2022]
Abstract
Previously, it was reported that human amniotic membrane (AM) induced stem cells from human deciduous exfoliated teeth (SHED) endothelial-like-cell differentiation. This interesting effect of AM matrix on SHED demands further elucidation. Objective of this in vitro work was to study the effect of 24-h VEGF induced on SHED endothelial differentiation when seeded on acellular stromal side (SS) of AM matrix. Stemness of SHED was identified by flow cytometry. Cell attachment and morphological changes towards the matrix was observed by scanning electron microscopy. Protein expression of endothelial marker was examined by Western blot. The expression of stem cells and endothelial-specific gene markers of VEGF-induced SHED cultured on human AM was inspected via reverse transcriptase-polymerase chain reaction. Results showed SHED at both passages retain stemness property. Ang-1 protein was expressed in SHED. Cells treated with VEGF and cultured on AM transformed attached well to AM. VEGF-induced SHED expressed both stem cell and endothelial-specific markers throughout the treatments and timeline. Interestingly, prolonged VEGF treatment increased the expression of Cox-2 and VE-Cadherin genes in all treated groups when compared to SHED. It was concluded that the VEGF-induced SHED showed better expression of endothelial-specific markers when cultured on SS of AM, with prolonged VEGF treatment.
Collapse
Affiliation(s)
- Muhammad Fuad Hilmi Yusof
- School of Dental Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Siti Nurnasihah Md Hashim
- School of Dental Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Wafa' Zahari
- School of Dental Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Hamshawagini Chandra
- School of Dental Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia
| | | | - Thirumulu Ponnuraj Kannan
- School of Dental Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia
- Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Suzina Sheikh Abdul Hamid
- Tissue Bank, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Khairani Idah Mokhtar
- Kulliyyah of Dentistry, International Islamic University Malaysia, 25200, Kuantan, Pahang, Malaysia
| | - Ahmad Azlina
- School of Dental Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia.
- Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia.
| |
Collapse
|
|
39
|
El Moshy S, Radwan IA, Rady D, Abbass MMS, El-Rashidy AA, Sadek KM, Dörfer CE, Fawzy El-Sayed KM. Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications. Stem Cells Int 2020; 2020:7593402. [PMID: 32089709 PMCID: PMC7013327 DOI: 10.1155/2020/7593402] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Revised: 12/23/2019] [Accepted: 01/10/2020] [Indexed: 12/13/2022] Open
Abstract
Regenerative medicine literature has proposed mesenchymal stem/progenitor cell- (MSC-) mediated therapeutic approaches for their great potential in managing various diseases and tissue defects. Dental MSCs represent promising alternatives to nondental MSCs, owing to their ease of harvesting with minimally invasive procedures. Their mechanism of action has been attributed to their cell-to-cell contacts as well as to the paracrine effect of their secreted factors, namely, secretome. In this context, dental MSC-derived secretome/conditioned medium could represent a unique cell-free regenerative and therapeutic approach, with fascinating advantages over parent cells. This article reviews the application of different populations of dental MSC secretome/conditioned medium in in vitro and in vivo animal models, highlights their significant implementation in treating different tissue' diseases, and clarifies the significant bioactive molecules involved in their regenerative potential. The analysis of these recent studies clearly indicate that dental MSCs' secretome/conditioned medium could be effective in treating neural injuries, for dental tissue regeneration, in repairing bone defects, and in managing cardiovascular diseases, diabetes mellitus, hepatic regeneration, and skin injuries, through regulating anti-inflammatory, antiapoptotic, angiogenic, osteogenic, and neurogenic mediators.
Collapse
Affiliation(s)
- Sara El Moshy
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Israa Ahmed Radwan
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Dina Rady
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Marwa M. S. Abbass
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Aiah A. El-Rashidy
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Biomaterials Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Khadiga M. Sadek
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Biomaterials Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Christof E. Dörfer
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
| | - Karim M. Fawzy El-Sayed
- Stem cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
- Oral Medicine and Periodontology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
| |
Collapse
|
|
40
|
El Gezawi M, Wölfle UC, Haridy R, Fliefel R, Kaisarly D. Remineralization, Regeneration, and Repair of Natural Tooth Structure: Influences on the Future of Restorative Dentistry Practice. ACS Biomater Sci Eng 2019; 5:4899-4919. [PMID: 33455239 DOI: 10.1021/acsbiomaterials.9b00591] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Currently, the principal strategy for the treatment of carious defects involves cavity preparations followed by the restoration of natural tooth structure with a synthetic material of inferior biomechanical and esthetic qualities and with questionable long-term clinical reliability of the interfacial bonds. Consequently, prevention and minimally invasive dentistry are considered basic approaches for the preservation of sound tooth structure. Moreover, conventional periodontal therapies do not always ensure predictable outcomes or completely restore the integrity of the periodontal ligament complex that has been lost due to periodontitis. Much effort and comprehensive research have been undertaken to mimic the natural development and biomineralization of teeth to regenerate and repair natural hard dental tissues and restore the integrity of the periodontium. Regeneration of the dentin-pulp tissue has faced several challenges, starting with the basic concerns of clinical applicability. Recent technologies and multidisciplinary approaches in tissue engineering and nanotechnology, as well as the use of modern strategies for stem cell recruitment, synthesis of effective biodegradable scaffolds, molecular signaling, gene therapy, and 3D bioprinting, have resulted in impressive outcomes that may revolutionize the practice of restorative dentistry. This Review covers the current approaches and technologies for remineralization, regeneration, and repair of natural tooth structure.
Collapse
Affiliation(s)
- Moataz El Gezawi
- Department of Restorative Dental Sciences, Imam Abdulrahman Bin Faisal University, Dammam 34221, Saudi Arabia
| | - Uta Christine Wölfle
- Department of Conservative Dentistry and Periodontology, University Hospital, LMU Munich, 80336 Munich, Germany
| | - Rasha Haridy
- Department of Clinical Dental Sciences, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia.,Department of Conservative Dentistry, Faculty of Oral and Dental Medicine, Cairo University, Cairo 11553, Egypt
| | - Riham Fliefel
- Experimental Surgery and Regenerative Medicine (ExperiMed), University Hospital, LMU Munich, 80336 Munich, Germany.,Department of Oral and Maxillofacial Surgery, University Hospital, LMU Munich, 80337 Munich, Germany.,Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Alexandria University, Alexandria 21526, Egypt
| | - Dalia Kaisarly
- Department of Conservative Dentistry and Periodontology, University Hospital, LMU Munich, 80336 Munich, Germany.,Biomaterials Department, Faculty of Oral and Dental Medicine, Cairo University, Cairo 11553, Egypt
| |
Collapse
|