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Stefańska K, Volponi AA, Kulus M, Waśko J, Farzaneh M, Grzelak J, Azizidoost S, Mozdziak P, Bukowska D, Antosik P, Zabel M, Podhorska-Okołów M, Dzięgiel P, Szcześniak M, Woszczyk M, Kempisty B. Dental pulp stem cells - A basic research and future application in regenerative medicine. Biomed Pharmacother 2024; 178:116990. [PMID: 39024839 DOI: 10.1016/j.biopha.2024.116990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 06/10/2024] [Accepted: 06/15/2024] [Indexed: 07/20/2024] Open
Abstract
Dental pulp is a valuable and accessible source of stem cells (DPSCs) with characteristics similar to mesenchymal stem cells. DPSCs can regenerate a range of tissues and their potential for clinical application in regenerative medicine is promising. DPSCs have been found to express low levels of Class II HLA-DR (MHC) molecules, making them potential candidates for allogeneic transplantation without matching the donor's tissue. Research on the correlation between non-coding RNAs (ncRNAs) and human dental pulp stem cells (DPSCs) provides promising insights into the use of these cells in clinical settings for a wide range of medical conditions. It is possible to use a number of ncRNAs in order to restore the functional role of downregulated ncRNAs that are correlated with osteoblastogenesis, or to suppress the functional role of overexpressed ncRNAs associated with osteoclast differentiation in some cases.
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Affiliation(s)
- Katarzyna Stefańska
- Cellivia 3 S.A., Poznan 60-529, Poland; Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan 60-781, Poland.
| | - Ana Angelova Volponi
- Centre for Craniofacial and Regenerative Biology, Dental Institute, King's College London, London WC2R 2LS, UK.
| | - Magdalena Kulus
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland.
| | | | - Maryam Farzaneh
- Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Joanna Grzelak
- Division of Anatomy, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw 50-368, Poland.
| | - Shirin Azizidoost
- Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Paul Mozdziak
- Prestage Department of Poultry Sciences, North Carolina State University, Raleigh, NC 27695, USA.
| | - Dorota Bukowska
- Department of Diagnostics and Clinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland.
| | - Paweł Antosik
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland.
| | - Maciej Zabel
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw 50-368, Poland; Division of Anatomy and Histology, University of Zielona Góra, Zielona Góra 65-046, Poland.
| | - Marzenna Podhorska-Okołów
- Division of Ultrastructural Research, Department of Human Morphology and Embryology, Wroclaw Medical University, Wroclaw 50-368, Poland.
| | - Piotr Dzięgiel
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw 50-368, Poland.
| | - Marta Szcześniak
- Department of Diagnostics, Poznan University of Medical Sciences, Bukowska 70, Poznań 60-812, Poland; Department of Maxillofacial Surgery, Poznan University of Medical Sciences, Przybyszewskiego 49, Poznań 60-355, Poland.
| | | | - Bartosz Kempisty
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland; Division of Anatomy, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw 50-368, Poland; College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC 27695, USA; Center of Assisted Reproduction, Department of Obstetrics and Gynecology, University Hospital and Masaryk University, Brno, Czech Republic
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Farshbaf A, Mottaghi M, Mohammadi M, Monsef K, Mirhashemi M, Attaran Khorasani A, Mohtasham N. Regenerative application of oral and maxillofacial 3D organoids based on dental pulp stem cell. Tissue Cell 2024; 89:102451. [PMID: 38936200 DOI: 10.1016/j.tice.2024.102451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 05/30/2024] [Accepted: 06/17/2024] [Indexed: 06/29/2024]
Abstract
Dental pulp stem cells (DPSCs) originate from the neural crest and the present mesenchymal phenotype showed self-renewal capabilities and can differentiate into at least three lineages. DPSCs are easily isolated with minimal harm, no notable ethical constraints, and without general anesthesia to the donor individuals. Furthermore, cryopreservation of DPSCs provides this opportunity for autologous transplantation in future studies without fundamental changes in stemness, viability, proliferation, and differentiating features. Current approaches for pulp tissue regeneration include pulp revascularization, cell-homing-based regenerative endodontic treatment (RET), cell-transplantation-based regenerative endodontic treatment, and allogeneic transplantation. In recent years, a novel technology, organoid, provides a mimic physiological condition and tissue construct that can be applied for tissue engineering, genetic manipulation, disease modeling, single-cell high throughput analysis, living biobank, cryopreserving and maintaining cells, and therapeutic approaches based on personalized medicine. The organoids can be a reliable preclinical prediction model for evaluating cell behavior, monitoring drug response or resistance, and comparing healthy and pathological conditions for therapeutic and prognostic approaches. In the current review, we focused on the promising application of 3D organoid technology based on DPSCs in oral and maxillofacial tissue regeneration. We discussed encountering challenges and limitations, and found promising solutions to overcome obstacles.
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Affiliation(s)
- Alieh Farshbaf
- Dental Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahtab Mottaghi
- School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mehdi Mohammadi
- Medical Informatics Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
| | - Kouros Monsef
- Dental Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Mirhashemi
- Department of Oral and Maxillofacial Pathology, and Oral and Maxillofacial Diseases Research Center, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Nooshin Mohtasham
- Oral and Maxillofacial Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Shah P, Aghazadeh M, Rajasingh S, Dixon D, Jain V, Rajasingh J. Stem cells in regenerative dentistry: Current understanding and future directions. J Oral Biosci 2024; 66:288-299. [PMID: 38403241 DOI: 10.1016/j.job.2024.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 02/15/2024] [Accepted: 02/18/2024] [Indexed: 02/27/2024]
Abstract
BACKGROUND Regenerative dentistry aims to enhance the structure and function of oral tissues and organs. Modern tissue engineering harnesses cell and gene-based therapies to advance traditional treatment approaches. Studies have demonstrated the potential of mesenchymal stem cells (MSCs) in regenerative dentistry, with some progressing to clinical trials. This review comprehensively examines animal studies that have utilized MSCs for various therapeutic applications. Additionally, it seeks to bridge the gap between related findings and the practical implementation of MSC therapies, offering insights into the challenges and translational aspects involved in transitioning from preclinical research to clinical applications. HIGHLIGHTS To achieve this objective, we have focused on the protocols and achievements related to pulp-dentin, alveolar bone, and periodontal regeneration using dental-derived MSCs in both animal and clinical studies. Various types of MSCs, including dental-derived cells, bone-marrow stem cells, and umbilical cord stem cells, have been employed in root canals, periodontal defects, socket preservation, and sinus lift procedures. Results of such include significant hard tissue reconstruction, functional pulp regeneration, root elongation, periodontal ligament formation, and cementum deposition. However, cell-based treatments for tooth and periodontium regeneration are still in early stages. The increasing demand for stem cell therapies in personalized medicine underscores the need for scientists and responsible organizations to develop standardized treatment protocols that adhere to good manufacturing practices, ensuring high reproducibility, safety, and cost-efficiency. CONCLUSION Cell therapy in regenerative dentistry represents a growing industry with substantial benefits and unique challenges as it strives to establish sustainable, long-term, and effective oral tissue regeneration solutions.
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Affiliation(s)
- Pooja Shah
- Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Marziyeh Aghazadeh
- Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Sheeja Rajasingh
- Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Douglas Dixon
- Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA; Department of Periodontology, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Vinay Jain
- Department of Prosthodontics, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Johnson Rajasingh
- Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA; Department of Medicine-Cardiology, University of Tennessee Health Science Center, Memphis, TN, USA; Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA.
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Wang M, He M, Xu X, Wu Z, Tao J, Yin F, Luo K, Jiang J. Cementum protein 1 gene-modified adipose-derived mesenchymal stem cell sheets enhance periodontal regeneration in osteoporosis rat. J Periodontal Res 2023. [PMID: 37154214 DOI: 10.1111/jre.13133] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 03/04/2023] [Accepted: 04/27/2023] [Indexed: 05/10/2023]
Abstract
BACKGROUND AND OBJECTIVES Osteoporosis (OP) and periodontitis are both diseases with excessive bone resorption, and the number of patients who suffer from these diseases is expected to increase. OP has been identified as a risk factor that accelerates the pathological process of periodontitis. Achieving effective and safe periodontal regeneration in OP patients is a meaningful challenge. This study aimed to assess the efficacy and biosecurity of human cementum protein 1 (hCEMP1) gene-modified cell sheets for periodontal fenestration defect regeneration in an OP rat model. MATERIALS AND METHODS Rat adipose-derived mesenchymal stem cells (rADSCs) were isolated from Sprague-Dawley rats. After primary culture, rADSCs were subjected to cell surface analysis and multi-differentiation assay. And rADSCs were transduced with hCEMP1 by lentiviral vector, and hCEMP1 gene-modified cell sheets were generated. The expression of hCEMP1 was evaluated by reverse transcription polymerase chain reaction and immunocytochemistry staining, and transduced cell proliferation was evaluated by Cell Counting Kit-8. The hCEMP1 gene-modified cell sheet structure was detected by histological analysis and scanning electron microscopy. Osteogenic and cementogenic-associated gene expression was evaluated by real-time quantitative polymerase chain reaction. In addition, an OP rat periodontal fenestration defect model was used to evaluate the regeneration effect of hCEMP1 gene-modified rADSC sheets. The efficacy was assessed with microcomputed tomography and histology, and the biosecurity of gene-modified cell sheets was evaluated by histological analysis of the spleen, liver, kidney and lung. RESULTS The rADSCs showed a phenotype of mesenchymal stem cells and possessed multi-differentiation capacity. The gene and protein expression of hCEMP1 through lentiviral transduction was confirmed, and there was no significant effect on rADSC proliferation. Overexpression of hCEMP1 upregulated osteogenic and cementogenic-related genes such as runt-related transcription factor 2, bone morphogenetic protein 2, secreted phosphoprotein 1 and cementum attachment protein in the gene-modified cell sheets. The fenestration lesions in OP rats treated with hCEMP1 gene-modified cell sheets exhibited complete bone bridging, cementum and periodontal ligament formation. Furthermore, histological sections of the spleen, liver, kidney and lung showed no evident pathological damage. CONCLUSION This pilot study demonstrates that hCEMP1 gene-modified rADSC sheets have a marked ability to enhance periodontal regeneration in OP rats. Thus, this approach may represent an effective and safe strategy for periodontal disease patients with OP.
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Affiliation(s)
- Meijie Wang
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
- Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
| | - Mengjiao He
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
- Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
| | - Xiongcheng Xu
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
- Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
| | - Zekai Wu
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
- Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
| | - Jing Tao
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
- Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
| | - Fan Yin
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
- Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
| | - Kai Luo
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
- Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
| | - Jun Jiang
- Institute of Stomatology & Laboratory of Oral Tissue Engineering, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
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Molecular Basis beyond Interrelated Bone Resorption/Regeneration in Periodontal Diseases: A Concise Review. Int J Mol Sci 2023; 24:ijms24054599. [PMID: 36902030 PMCID: PMC10003253 DOI: 10.3390/ijms24054599] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/19/2023] [Accepted: 02/06/2023] [Indexed: 03/02/2023] Open
Abstract
Periodontitis is the sixth most common chronic inflammatory disease, destroying the tissues supporting the teeth. There are three distinct stages in periodontitis: infection, inflammation, and tissue destruction, where each stage has its own characteristics and hence its line of treatment. Illuminating the underlying mechanisms of alveolar bone loss is vital in the treatment of periodontitis to allow for subsequent reconstruction of the periodontium. Bone cells, including osteoclasts, osteoblasts, and bone marrow stromal cells, classically were thought to control bone destruction in periodontitis. Lately, osteocytes were found to assist in inflammation-related bone remodeling besides being able to initiate physiological bone remodeling. Furthermore, mesenchymal stem cells (MSCs) either transplanted or homed exhibit highly immunosuppressive properties, such as preventing monocytes/hematopoietic precursor differentiation and downregulating excessive release of inflammatory cytokines. In the early stages of bone regeneration, an acute inflammatory response is critical for the recruitment of MSCs, controlling their migration, and their differentiation. Later during bone remodeling, the interaction and balance between proinflammatory and anti-inflammatory cytokines could regulate MSC properties, resulting in either bone formation or bone resorption. This narrative review elaborates on the important interactions between inflammatory stimuli during periodontal diseases, bone cells, MSCs, and subsequent bone regeneration or bone resorption. Understanding these concepts will open up new possibilities for promoting bone regeneration and hindering bone loss caused by periodontal diseases.
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The Role and Involvement of Stem Cells in Periodontology. Biomedicines 2023; 11:biomedicines11020387. [PMID: 36830924 PMCID: PMC9953576 DOI: 10.3390/biomedicines11020387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 01/25/2023] [Indexed: 01/31/2023] Open
Abstract
Periodontitis is a widespread inflammatory condition, characterized by a progressive deterioration of the supporting structures of the teeth. Due to the complexity of periodontal tissue and the surrounding inflammatory microenvironment, the repair of lesions at this level represents a continuous challenge. The regeneration of periodontal tissues is considered a promising strategy. Stem cells have remarkable properties, such as immunomodulatory potential, proliferation, migration, and multilineage differentiation. Thus, they can be used to repair tissue damage and reduce inflammation, potentially leading to periodontal regeneration. Among the stem cells used for periodontal regeneration, we studied dental mesenchymal stem cells (DMSCs), non-dental stem cells, and induced pluripotent stem cells (IPSCs). Although these cells have well documented important physiological characteristics, their use in contemporary practice to repair the affected periodontium is still a challenge.
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Moeenzade N, Naseri M, Osmani F, Emadian Razavi F. Dental pulp stem cells for reconstructing bone defects: A systematic review and meta-analysis. J Dent Res Dent Clin Dent Prospects 2022; 16:204-220. [PMID: 37560493 PMCID: PMC10407871 DOI: 10.34172/joddd.2022.034] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 12/02/2022] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND Bone reconstruction with appropriate quality and quantity for dental implant replacement in the alveolar ridge is a challenge in dentistry. As dental pulp stem cells (DPSCs) could be a new perspective in bone regeneration in the future, this study investigated the bone regeneration process by DPSCs. METHODS Electronic searches for articles in the PubMed, EMBASE, and Scopus databases were completed until 21 April 2022. The most important inclusion criteria for selecting in vivo studies reporting quantitative data based on new bone volume and new bone area. The quality assessment was performed based on Cochrane's checklist. RESULTS After the title, abstract, and full-text screening of 762 studies, 23 studies were included. A meta-analysis of 70 studies that reported bone regeneration based on new bone area showed a statistically significant favorable influence on bone tissue regeneration compared to the control groups (P<0.00001, standardized mean difference [SMD]=2.40, 95% CI: 1.55‒3.26; I2=83%). Also, the meta-analysis of 14 studies that reported new bone regeneration based on bone volume showed a statistically significant favorable influence on bone tissue regeneration compared to the control groups (P=0.0003, SMD=1.85, 95% CI: 0.85‒2.85; I2=84%). CONCLUSION This systematic review indicated that DPSCs in tissue regeneration therapy significantly affected bone tissue complex regeneration. However, more and less diverse preclinical studies will enable more powerful meta-analyses in the future.
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Affiliation(s)
- Neda Moeenzade
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Mohsen Naseri
- Cellular and Molecular Research Center, Department of Molecular Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Fereshteh Osmani
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Fariba Emadian Razavi
- Clinical Research Development Unit, School of Dentistry, Birjand University of Medical Sciences, Birjand, Iran
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Increasing Odontoblast-like Differentiation from Dental Pulp Stem Cells through Increase of β-Catenin/p-GSK-3β Expression by Low-Frequency Electromagnetic Field. Biomedicines 2021; 9:biomedicines9081049. [PMID: 34440255 PMCID: PMC8392719 DOI: 10.3390/biomedicines9081049] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 08/08/2021] [Accepted: 08/17/2021] [Indexed: 11/16/2022] Open
Abstract
Odontoblasts produce proteins that form the dentinal extracellular matrix, which can protect the dental pulp from external stimuli and is required for tooth regeneration. This study showed that a pulsed electromagnetic field (PEMF) can regulate cell metabolism and induce cell differentiation. This study determined the frequency of PEMF that is effective for odontoblast differentiation. Human dental pulp stem cells (hDPSCs) were cultured in odontoblast differentiation medium containing dexamethasone, BMP2, TGF-β1, and FGF-2, and then exposed to 10 mT intensity of PEMF at 40, 60, 70, and 150 Hz for 15 min/day. The MTT assay, LDH assay, flow cytometry, protein and gene expression, and immunofluorescence were performed to check if hDPSCs differentiated into odontoblast-like cells. The hDPSCs showed frequency-dependent differences in protein and gene expression. The mesenchymal stem cell markers were reduced to a greater extent at 60 and 70 Hz than at other frequencies, and odontoblast-related markers, particularly β-catenin, p-GSK-3β, and p-p38, were increased at 60 and 70 Hz. Exposure to 10 mT intensity of PEMF at 70 Hz influenced the differentiation of hDPSCs considerably. Taken together, PEMF treatment can promote differentiation of hDPSCs into odontoblast-like cells by increasing p-GSK-3β and β-catenin expression.
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Grawish ME, Saeed MA, Sultan N, Scheven BA. Therapeutic applications of dental pulp stem cells in regenerating dental, periodontal and oral-related structures. World J Meta-Anal 2021; 9:176-192. [DOI: 10.13105/wjma.v9.i2.176] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/13/2021] [Accepted: 04/23/2021] [Indexed: 02/06/2023] Open
Abstract
Dental pulp stem cells (DPSCs) have emerged as a promising tool with great potential for use in tissue regeneration and engineering. Some of the main advantages of these cells are their multifaceted differentiation capacity, along with their high proliferation rate, a relative simplicity of extraction and culture that enables obtaining patient-specific cell lines for their use in autologous cell therapy. PubMed, Scopus and Google Scholar databases were searched for relevant articles related to the use of DPSCs in regeneration of dentin-pulp complex (DPC), periodontal tissues, salivary gland and craniomaxillofacial bone defects. Few studies were found regarding the use of DPSCs for regeneration of DPC. Scaffold-based combined with DPSCs isolated from healthy pulps was the strategy used for DPC regeneration. Studies involved subcutaneous implantation of scaffolds loaded with DPSCs pretreated with odontogenic media, or performed on human tooth root model as a root slice. Most of the studies were related to periodontal tissue regeneration which mainly utilized DPSCs/secretome. For periodontal tissues, DPSCs or their secretome were isolated from healthy or inflamed pulps and they were used either for preclinical or clinical studies. Regarding salivary gland regeneration, the submandibular gland was the only model used for the preclinical studies and DPSCs or their secretome were isolated only from healthy pulps and they were used in preclinical studies. Likewise, DPSCs have been studied for craniomaxillofacial bone defects in the form of mandibular, calvarial and craniofacial bone defects where DPSCs were isolated only from healthy pulps for preclinical and clinical studies. From the previous results, we can conclude that DPSCs is promising candidate for dental and oral tissue regeneration.
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Affiliation(s)
- Mohammed E Grawish
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura 35516, Egypt
- Department of Oral Biology, Faculty of Oral and Dental Medicine, Delta University for Science and Technology, Mansoura 11152, Egypt
| | - Mahmoud A Saeed
- Department of Oral Biology, Faculty of Oral and Dental Medicine, Delta University for Science and Technology, Mansoura 11152, Egypt
| | - Nessma Sultan
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura 35516, Egypt
| | - Ben A Scheven
- School of Dentistry, Oral Biology, College of Medical and Dental Sciences, University of Birmingham, Birmingham B5 7EG, United Kingdom
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Grawish ME, Saeed MA, Sultan N, Scheven BA. Therapeutic applications of dental pulp stem cells in regenerating dental, periodontal and oral-related structures. World J Meta-Anal 2021; 9:175-191. [DOI: 10.13105/wjma.v9.i2.175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Angiogenesis in Regenerative Dentistry: Are We Far Enough for Therapy? Int J Mol Sci 2021; 22:ijms22020929. [PMID: 33477745 PMCID: PMC7832295 DOI: 10.3390/ijms22020929] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 01/14/2021] [Accepted: 01/15/2021] [Indexed: 12/14/2022] Open
Abstract
Angiogenesis is a broad spread term of high interest in regenerative medicine and tissue engineering including the dental field. In the last two decades, researchers worldwide struggled to find the best ways to accelerate healing, stimulate soft, and hard tissue remodeling. Stem cells, growth factors, pathways, signals, receptors, genetics are just a few words that describe this area in medicine. Dental implants, bone and soft tissue regeneration using autologous grafts, or xenografts, allografts, their integration and acceptance rely on their material properties. However, the host response, through its vascularization, plays a significant role. The present paper aims to analyze and organize the latest information about the available dental stem cells, the types of growth factors with pro-angiogenic effect and the possible therapeutic effect of enhanced angiogenesis in regenerative dentistry.
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Synthetic Scaffold/Dental Pulp Stem Cell (DPSC) Tissue Engineering Constructs for Bone Defect Treatment: An Animal Studies Literature Review. Int J Mol Sci 2020; 21:ijms21249765. [PMID: 33371390 PMCID: PMC7767470 DOI: 10.3390/ijms21249765] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 12/14/2020] [Accepted: 12/17/2020] [Indexed: 12/11/2022] Open
Abstract
Background: Recently a greater interest in tissue engineering for the treatment of large bone defect has been reported. The aim of the present systematic review and meta-analysis was to investigate the effectiveness of dental pulp stem cells and synthetic block complexes for bone defect treatment in preclinical in vivo articles. Methods: The electronic database and manual search was conducted on Pubmed, Scopus, and EMBASE. The papers identified were submitted for risk-of-bias assessment and classified according to new bone formation, bone graft characteristics, dental pulp stem cells (DPSCs) culture passages and amount of experimental data. The meta-analysis assessment was conducted to assess new bone formation in test sites with DPSCs/synthetic blocks vs. synthetic block alone. Results: The database search identified a total of 348 papers. After the initial screening, 30 studies were included, according to the different animal models: 19 papers on rats, 3 articles on rabbits, 2 manuscripts on sheep and 4 papers on swine. The meta-analysis evaluation showed a significantly increase in new bone formation in favor of DPSCs/synthetic scaffold complexes, if compared to the control at 4 weeks (Mean Diff: 17.09%, 95% CI: 15.16–18.91%, p < 0.01) and at 8 weeks (Mean Diff: 14.86%, 95% CI: 1.82–27.91%, p < 0.01) in rats calvaria bone defects. Conclusion: The synthetic scaffolds in association of DPSCs used for the treatment of bone defects showed encouraging results of early new bone formation in preclinical animal studies and could represent a useful resource for regenerative bone augmentation procedures
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In Vitro Mechanical and Biological Properties of 3D Printed Polymer Composite and β-Tricalcium Phosphate Scaffold on Human Dental Pulp Stem Cells. MATERIALS 2020; 13:ma13143057. [PMID: 32650530 PMCID: PMC7412522 DOI: 10.3390/ma13143057] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/26/2020] [Accepted: 07/06/2020] [Indexed: 12/14/2022]
Abstract
3D printed biomaterials have been extensively investigated and developed in the field of bone regeneration related to clinical issues. However, specific applications of 3D printed biomaterials in different dental areas have seldom been reported. In this study, we aimed to and successfully fabricated 3D poly (lactic-co-glycolic acid)/β-tricalcium phosphate (3D-PLGA/TCP) and 3D β-tricalcium phosphate (3D-TCP) scaffolds using two relatively distinct 3D printing (3DP) technologies. Conjunctively, we compared and investigated mechanical and biological responses on human dental pulp stem cells (hDPSCs). Physicochemical properties of the scaffolds, including pore structure, chemical elements, and compression modulus, were characterized. hDPSCs were cultured on scaffolds for subsequent investigations of biocompatibility and osteoconductivity. Our findings indicate that 3D printed PLGA/TCP and β-tricalcium phosphate (β-TCP) scaffolds possessed a highly interconnected and porous structure. 3D-TCP scaffolds exhibited better compressive strength than 3D-PLGA/TCP scaffolds, while the 3D-PLGA/TCP scaffolds revealed a flexible mechanical performance. The introduction of 3D structure and β-TCP components increased the adhesion and proliferation of hDPSCs and promoted osteogenic differentiation. In conclusion, 3D-PLGA/TCP and 3D-TCP scaffolds, with the incorporation of hDPSCs as a personalized restoration approach, has a prospective potential to repair minor and critical bone defects in oral and maxillofacial surgery, respectively.
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Immunomodulatory Properties of Stem Cells in Periodontitis: Current Status and Future Prospective. Stem Cells Int 2020; 2020:9836518. [PMID: 32724318 PMCID: PMC7366217 DOI: 10.1155/2020/9836518] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 05/02/2020] [Accepted: 05/08/2020] [Indexed: 02/05/2023] Open
Abstract
Periodontitis is the sixth-most prevalent chronic inflammatory disease and gradually devastates tooth-supporting tissue. The complexity of periodontal tissue and the local inflammatory microenvironment poses great challenges to tissue repair. Recently, stem cells have been considered a promising strategy to treat tissue damage and inflammation because of their remarkable properties, including stemness, proliferation, migration, multilineage differentiation, and immunomodulation. Several varieties of stem cells can potentially be applied to periodontal regeneration, including dental mesenchymal stem cells (DMSCs), nonodontogenic stem cells, and induced pluripotent stem cells (iPSCs). In particular, these stem cells possess extensive immunoregulatory capacities. In periodontitis, these cells can exert anti-inflammatory effects and regenerate the periodontium. Stem cells derived from infected tissue possess typical stem cell characteristics with lower immunogenicity and immunosuppression. Several studies have demonstrated that these cells can also regenerate the periodontium. Furthermore, the interaction of stem cells with the surrounding infected microenvironment is critical to periodontal tissue repair. Though the immunomodulatory capabilities of stem cells are not entirely clarified, they show promise for therapeutic application in periodontitis. Here, we summarize the potential of stem cells for periodontium regeneration in periodontitis and focus on their characteristics and immunomodulatory properties as well as challenges and perspectives.
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Pranskunas M, Galindo-Moreno P, Padial-Molina M. Extraction Socket Preservation Using Growth Factors and Stem Cells: a Systematic Review. EJOURNAL OF ORAL MAXILLOFACIAL RESEARCH 2019; 10:e7. [PMID: 31620269 PMCID: PMC6788421 DOI: 10.5037/jomr.2019.10307] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 09/05/2019] [Indexed: 12/24/2022]
Abstract
Objectives To evaluate the reported literature on the use of stem cells or growth factors for post extraction treatment of the alveolar bone. Material and Methods A NCBI PubMed and PubMed Central databases search was conducted between September 2010 and August 2018, to identify animal or clinical studies reporting the clinical, radiographical and/or histological outcomes of socket preservation techniques after applying mesenchymal stem cells or growth factors. Only studies published in English language in the last 10 years were included in the study. Results Eleven studies were identified fulfilling the inclusion criteria. They evaluate a total of 386 post extraction sockets. The main tested materials identified in the current review were bone morphogenetic protein-2 - 3 studies and mesenchymal stem cells - 3 studies. Other comparators were bone morphogenetic protein-9, platelet-derived growth factor-BB homodimers and bone marrow. Overall evaluation indicate positive results for all test groups showing differences in final socket width between 0.64 and 1.28 mm favouring the test groups. Histologically, no particular differences are detected between test and control groups. Most of the studies present low risk of bias. Conclusions In general, the use of mesenchymal stem cells or bioactive osteogenic molecules favours bone regeneration after tooth extraction, as evaluated clinically, radiographically and histologically. However, specific differences that support particular recommendations are still unclear in light of the current published evidence. Future studies should include the standardization of the mesenchymal stem cells selection and purification as well as dosage and delivery methods of bioactive molecules.
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Affiliation(s)
- Mindaugas Pranskunas
- Department of Oral and Maxillofacial Surgery, Faculty of Odontology, Medical Academy, Lithuanian University of Health Sciences, KaunasLithuania
| | - Pablo Galindo-Moreno
- Department of Oral Surgery and Implant Dentistry. School of Dentistry, University of Granada, GranadaSpain
| | - Miguel Padial-Molina
- Department of Oral Surgery and Implant Dentistry. School of Dentistry, University of Granada, GranadaSpain
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