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Dai P, Qi G, Zhu M, Du Q, Wang K, Gao Y, Li M, Feng X, Zhang X. Periodontal ligament stem cell tissue engineering scaffolds can guide and promote canine periodontal tissue regeneration. Front Vet Sci 2024; 11:1465879. [PMID: 39444741 PMCID: PMC11496256 DOI: 10.3389/fvets.2024.1465879] [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: 07/17/2024] [Accepted: 09/24/2024] [Indexed: 10/25/2024] Open
Abstract
Background The immunogenicity of allogeneic mesenchymal stem cells (MSCs) is significantly enhanced after transplantation or differentiation, and these cells can be recognized and cleared by recipient immune cells. Graft rejection has become a major obstacle to improving the therapeutic effect of allogeneic MSCs or, after their differentiation, transplantation in the treatment of diabetes and other diseases. Solving this problem is helpful for prolonging the time that cells play a role in the recipient body and for significantly improving the clinical therapeutic effect. Methods In this study, canine adipose-derived mesenchymal stem cells (ADSCs) were used as seed cells, and gene editing technology was used to knock out the B2M gene in these cells and cooperate with the overexpression of the PD-L1 gene. Gene-edited ADSCs (GeADSCs), whose biological characteristics and safety are not different from those of normal canine ADSCs, have been obtained. Results The immunogenicity of GeADSCs is reduced, the immune escape ability of GeADSCs is enhanced, and GeADSCs can remain in the body for a longer time. Using the optimized induction program, the efficiency of the differentiation of GeADSCs into new islet β-cells was increased, and the maturity of the new islet β-cells was increased. The immunogenicity of new islet β-cells decreased, and their immune escape ability was enhanced after the cells were transplanted into diabetic dogs (the graft site was prevascularized by the implantation of a scaffold to form a vascularized pouch). The number of infiltrating immune cells and the content of immune factors were decreased at the graft site. Conclusions New islet β-cell transplantation, which has low immunogenicity, can reverse diabetes in dogs, and the therapeutic effect of cell transplantation is significantly enhanced. This study provides a new method for prolonging the survival and functional time of cells in transplant recipients and significantly improving the clinical therapeutic effect.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Xinke Zhang
- The College of Veterinary Medicine, Northwest Agriculture and Forestry University, Yangling, China
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Miteva M, Mihaylova Z, Mitev V, Aleksiev E, Stanimirov P, Praskova M, Dimitrova VS, Vasileva A, Calenic B, Constantinescu I, Perlea P, Ishkitiev N. A Review of Stem Cell Attributes Derived from the Oral Cavity. Int Dent J 2024; 74:1129-1141. [PMID: 38582718 PMCID: PMC11561491 DOI: 10.1016/j.identj.2024.03.008] [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: 02/29/2024] [Accepted: 03/12/2024] [Indexed: 04/08/2024] Open
Abstract
Oral cavity stem cells (OCSCs) have been the focus of intense scientific efforts due to their accessibility and stem cell properties. The present work aims to compare the different characteristics of 6 types of dental stem cells derived from the oral cavity: dental pulp stem cells (DPSC), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSC), stem cells from the apical papilla (SCAP), bone marrow mesenchymal stem cells (BMSC), and gingival mesenchymal stem cells (GMSC). Using immunofluorescence and real-time polymerase chain reaction techniques, we analysed the cells for stem cell, differentiation, adhesion, and extracellular matrix markers; the ability to proliferate in vitro; and multilineage differentiation potential. Markers such as vimentin, CD44, alkaline phosphatase, CD146, CD271, CD49f, Oct 3/4, Sox 9, FGF7, nestin, and BMP4 showed significant differences in expression levels, highlighting the heterogeneity and unique characteristics of each cell type. At the same time, we confirmed that all cell types successfully differentiated into osteogenic, chondrogenic, or adipose lineages, with different readiness. In conclusion, our study reveals the distinct properties and potential applications of various dental-derived stem cells. These findings contribute to a deeper understanding of OCSCs and their significance in future clinical applications.
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Affiliation(s)
- Marina Miteva
- Department of Chemistry and Biochemistry, Medical Faculty, Medical University Sofia, Bulgaria
| | - Zornitsa Mihaylova
- Department of Dental, Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Medical University Sofia, Bulgaria
| | - Vanyo Mitev
- Department of Chemistry and Biochemistry, Medical Faculty, Medical University Sofia, Bulgaria
| | - Evgeniy Aleksiev
- Department of Dental, Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Medical University Sofia, Bulgaria
| | - Pavel Stanimirov
- Department of Dental, Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Medical University Sofia, Bulgaria
| | - Maria Praskova
- Department of Chemistry and Biochemistry, Medical Faculty, Medical University Sofia, Bulgaria
| | - Violeta S Dimitrova
- Department of Chemistry and Biochemistry, Medical Faculty, Medical University Sofia, Bulgaria
| | - Anelia Vasileva
- Department of Chemistry and Biochemistry, Medical Faculty, Medical University Sofia, Bulgaria
| | - Bogdan Calenic
- Centre for Immunogenetics and Virology, Fundeni Clinical Institute, University of Medicine and Farmacy "Carol Davila," Bucharest, Romania.
| | - Ileana Constantinescu
- Centre for Immunogenetics and Virology, Fundeni Clinical Institute, University of Medicine and Farmacy "Carol Davila," Bucharest, Romania
| | - Paula Perlea
- Department of Endodontics, UMF Carol Davila, Bucharest, Romania.
| | - Nikolay Ishkitiev
- Department of Chemistry and Biochemistry, Medical Faculty, Medical University Sofia, Bulgaria
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Balaban YE, Akbaba S, Bozkurt SB, Buyuksungur A, Akgun EE, Gonen ZB, Salkin H, Tezcaner A, Hakki SS. Local application of gingiva-derived mesenchymal stem cells on experimental periodontitis in rats. J Periodontol 2024; 95:456-468. [PMID: 37787060 DOI: 10.1002/jper.23-0246] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 07/24/2023] [Accepted: 09/04/2023] [Indexed: 10/04/2023]
Abstract
BACKGROUND Stem cell-based approaches in regenerative periodontal therapy have been used in different experimental models. In this study, the effect of local application of gingival mesenchymal stem cells (GMSC) in fibroin/chitosan oligosaccharide lactate hydrogel (F/COS) on periodontal regeneration was evaluated using experimental periodontitis model in rats. METHODS Mesenchymal stem cells were isolated from the gingiva of rats and characterized. Viability tests and confocal imaging of GMSC in hydrogels were performed. Healthy control without periodontitis (Health; H; n=10), control with periodontitis but no application (Periodontitis; P; n=10), only hydrogel application (F/COS; n=10), and GMSC+F/COS (n=10) four groups were formed for in vivo studies. Experimental periodontitis was created with silk sutures around the maxillary second molars. GMSC labeled with green fluorescent protein (GFP) (250,000 cells/50 μL) in F/COS were applied to the defect. Animals were sacrificed at 2nd and 8th weeks and maxillae of the animals were evaluated by micro-computed tomography (micro-CT) and histologically. The presence of GFP-labeled GMSC was confirmed at the end of 8 weeks. RESULTS Micro-CT analysis showed statistically significant new bone formation in the F/COS+GMSC treated group compared with the P group at the end of 8 weeks (p < 0.05). New bone formation was also observed in the F/COS group, but the statistical analysis revealed that this difference was not significant when compared with the P group (p > 0.05). Long junctional epithelium formation was less in the F/COS+GMSC group compared with the P group. Periodontal ligament and connective tissue were well-organized in F/COS+GMSC group. CONCLUSION The results showed that local GMSC application in hydrogel contributed to the formation of new periodontal ligament and alveolar bone in rats with experimental periodontitis. Since gingiva is easly accessible tissue, it is promising for autologous cell-based treatments in clinical applications.
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Affiliation(s)
- Yunus Emre Balaban
- Faculty of Dentistry, Department of Periodontology, Selcuk University, Konya, Turkey
| | - Sema Akbaba
- Department of Biotechnology, Middle East Technical University, Ankara, Turkey
| | - Serife Buket Bozkurt
- Department of Biochemistry, Niğde Ömer Halisdemir University Faculty of Medicine, Niğde, Turkey
| | - Arda Buyuksungur
- Faculty of Dentistry, Basic Medical Sciences, Ankara University, Ankara, Turkey
| | - E Ece Akgun
- Department of Histology and Embryology, Afyon Kocatepe University Faculty of Veterinary Medicine, Afyonkarahisar, Turkey
| | | | - Hasan Salkin
- Department of Medical Services and Techniques, Program of Pathology Laboratory Techniques, Vocational School, Beykent University, Istanbul, Turkey
| | - Aysen Tezcaner
- Department of Engineering Sciences, Middle East Technical University, Ankara, Turkey
| | - Sema S Hakki
- Faculty of Dentistry, Department of Periodontology, Selcuk University, Konya, Turkey
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Medhat A, El-Zainy MA, Fathy I. Photo biomodulation of dental derived stem cells to ameliorate regenerative capacity: In vitro study. Saudi Dent J 2024; 36:347-352. [PMID: 38419992 PMCID: PMC10897600 DOI: 10.1016/j.sdentj.2023.11.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Revised: 11/13/2023] [Accepted: 11/15/2023] [Indexed: 03/02/2024] Open
Abstract
Background Dental regeneration benefits from improving the features of dental derived stem cells. Gallium-aluminum-arsenide laser had a significant role in modification of cell behavior in different cell lines and culture conditions. Hence, exploring its mechanism and effect on dental derived stem cells would benefit prospective regenerative dental therapies. Objectives To assess the impact of photo biomodulation by Low-Level-Laser on isolated Dental Pulp derived Stem Cells and Periodontal Ligament derived Stem Cells regarding their proliferation and osteogenic differentiation. Methods Isolated DPSCs and PDLSCs from impacted third molars were subjected to Gallium-aluminum-arsenide laser for 12 sec and 3.6 J/cm2. The proliferative capacity was evaluated via 3-(4,5-dimethylthiazol-2-yl),2,5-diphenyltetrazolium bromide (MTT) Assay and Trypan blue stain. Cell osteogenic differentiation potentials were assessed by alkaline phosphatase assay and alizarin red stain, polymerase chain reaction was performed to quantify Nuclear factor Kappa gene expression. Results DPSCs subjected to laser bio-stimulation showed the best results regarding cell viability (MTT) and osteogenic differentiation (ALP assay), and calcium deposition at 3 intervals (3, 7, 14 days), meanwhile, PDLSCs subjected to laser bio-stimulation showed better result than control but less than DPSCs. While NF-KB gene expression was proven to be approximately comparable for both groups. Generally, the Photo-bio modulated groups showed better results than their control groups. Conclusion Low-level laser bio-stimulation (LLL) therapy improves DPSC and PDLSC osteogenic differentiation and proliferation via the activation of the NF-KB pathway. Also, the DPSCs outperformed PDLSCs in terms of performance. Clinical significance These results can be beneficial information and a reference database for more research in tissue engineering, dental therapy, and regeneration.
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Affiliation(s)
- Alaa Medhat
- Department of Oral Biology, Faculty of Dentistry, Ain-Shams University, Cairo, Egypt
| | - Medhat A El-Zainy
- Department of Oral Biology, Faculty of Dentistry, Ain-Shams University, Cairo, Egypt
| | - Iman Fathy
- Department of Oral Biology, Faculty of Dentistry, Ain-Shams University, Cairo, Egypt
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Duman BÖ, Yazir Y, Halbutoğullari ZS, Mert S, Öztürk A, Gacar G, Duruksu G. Production of alginate macrocapsule device for long-term normoglycaemia in the treatment of type 1 diabetes mellitus with pancreatic cell sheet engineering. Biomed Mater 2024; 19:025008. [PMID: 38194706 DOI: 10.1088/1748-605x/ad1c9b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 01/09/2024] [Indexed: 01/11/2024]
Abstract
Type 1 diabetes-mellitus (T1DM) is characterized by damage of beta cells in pancreatic islets. Cell-sheet engineering, one of the newest therapeutic approaches, has also been used to create functional islet systems by creating islet/beta cell-sheets and transferring these systems to areas that require minimally invasive intervention, such as extrahepatic areas. Since islets, beta cells, and pancreas transplants are allogeneic, immune problems such as tissue rejection occur after treatment, and patients become insulin dependent again. In this study, we aimed to design the most suitable cell-sheet treatment method and macrocapsule-device that could provide long-term normoglycemia in rats. Firstly, mesenchymal stem cells (MSCs) and beta cells were co-cultured in a temperature-responsive culture dish to obtain a cell-sheet and then the cell-sheets macroencapsulated using different concentrations of alginate. The mechanical properties and pore sizes of the macrocapsule-device were characterized. The viability and activity of cell-sheets in the macrocapsule were evaluatedin vitroandin vivo. Fasting blood glucose levels, body weight, and serum insulin & C-peptide levels were evaluated after transplantation in diabetic-rats. After the transplantation, the blood glucose level at 225 mg dl-1on the 10th day dropped to 168 mg dl-1on the 15th day, and remained at the normoglycemic level for 210 days. In this study, an alginate macrocapsule-device was successfully developed to protect cell-sheets from immune attacks after transplantation. The results of our study provide the basis for future animal and human studies in which this method can be used to provide long-term cellular therapy in T1DM patients.
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Affiliation(s)
- Büşra Öncel Duman
- European Vocational School, Medical Laboratory Techniques Program, Kocaeli Health and Technology University, 41030 Kocaeli, Turkey
| | - Yusufhan Yazir
- Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University (KOGEM), TR41001 Izmit, Kocaeli, Turkey
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey
- Department of Histology and Embryology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
| | - Zehra Seda Halbutoğullari
- Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University (KOGEM), TR41001 Izmit, Kocaeli, Turkey
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey
- Department of Medical Biology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
| | - Serap Mert
- Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University (KOGEM), TR41001 Izmit, Kocaeli, Turkey
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey
- Department of Chemistry and Chemical Processing Technology, Kocaeli University, Kocaeli, Turkey
- Department of Polymer Science and Technology, Kocaeli University, Kocaeli, Turkey
| | - Ahmet Öztürk
- Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University (KOGEM), TR41001 Izmit, Kocaeli, Turkey
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey
- Department of Histology and Embryology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
| | - Gülçin Gacar
- Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University (KOGEM), TR41001 Izmit, Kocaeli, Turkey
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey
| | - Gökhan Duruksu
- Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University (KOGEM), TR41001 Izmit, Kocaeli, Turkey
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey
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Kadkhoda Z, Motie P, Rad MR, Mohaghegh S, Kouhestani F, Motamedian SR. Comparison of Periodontal Ligament Stem Cells with Mesenchymal Stem Cells from Other Sources: A Scoping Systematic Review of In vitro and In vivo Studies. Curr Stem Cell Res Ther 2024; 19:497-522. [PMID: 36397622 DOI: 10.2174/1574888x17666220429123319] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 12/31/2021] [Accepted: 03/11/2022] [Indexed: 11/22/2022]
Abstract
OBJECTIVE The application of stem cells in regenerative medicine depends on their biological properties. This scoping review aimed to compare the features of periodontal ligament stem cells (PDLSSCs) with stem cells derived from other sources. DESIGN An electronic search in PubMed/Medline, Embase, Scopus, Google Scholar and Science Direct was conducted to identify in vitro and in vivo studies limited to English language. RESULTS Overall, 65 articles were included. Most comparisons were made between bone marrow stem cells (BMSCs) and PDLSCs. BMSCs were found to have lower proliferation and higher osteogenesis potential in vitro and in vivo than PDLSCs; on the contrary, dental follicle stem cells and umbilical cord mesenchymal stem cells (UCMSCs) had a higher proliferative ability and lower osteogenesis than PDLSCs. Moreover, UCMSCs exhibited a higher apoptotic rate, hTERT expression, and relative telomerase length. The immunomodulatory function of adipose-derived stem cells and BMSCs was comparable to PDLSCs. Gingival mesenchymal stem cells showed less sensitivity to long-term culture. Both pure and mixed gingival cells had lower osteogenic ability compared to PDLSCs. Comparison of dental pulp stem cells (DPSCs) with PDLSCs regarding proliferation rate, osteo/adipogenesis, and immunomodulatory properties was contradictory; however, in vivo bone formation of DPSCs seemed to be lower than PDLSCs. CONCLUSION In light of the performed comparative studies, PDLSCs showed comparable results to stem cells derived from other sources; however, further in vivo studies are needed to determine the actual pros and cons of stem cells in comparison to each other.
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Affiliation(s)
- Zeinab Kadkhoda
- Department of Periodontology, School of Dentistry, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Parisa Motie
- Student Research Committee, School of Dentistry, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Maryam Rezaei Rad
- Dental Research Center, Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sadra Mohaghegh
- Student Research Committee, School of Dentistry, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Farnaz Kouhestani
- Department of Periodontics, School of Dentistry, Bushehr University of Medical Sciences, Tehran, Iran
| | - Saeed Reza Motamedian
- Dentofacial Deformities Research Center, Research Institute of Dental Sciences, Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Bai X, Cao R, Wu D, Zhang H, Yang F, Wang L. Dental Pulp Stem Cells for Bone Tissue Engineering: A Literature Review. Stem Cells Int 2023; 2023:7357179. [PMID: 37868704 PMCID: PMC10586346 DOI: 10.1155/2023/7357179] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 06/03/2023] [Accepted: 09/19/2023] [Indexed: 10/24/2023] Open
Abstract
Bone tissue engineering (BTE) is a promising approach for repairing and regenerating damaged bone tissue, using stem cells and scaffold structures. Among various stem cell sources, dental pulp stem cells (DPSCs) have emerged as a potential candidate due to their multipotential capabilities, ability to undergo osteogenic differentiation, low immunogenicity, and ease of isolation. This article reviews the biological characteristics of DPSCs, their potential for BTE, and the underlying transcription factors and signaling pathways involved in osteogenic differentiation; it also highlights the application of DPSCs in inducing scaffold tissues for bone regeneration and summarizes animal and clinical studies conducted in this field. This review demonstrates the potential of DPSC-based BTE for effective bone repair and regeneration, with implications for clinical translation.
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Affiliation(s)
- Xiaolei Bai
- Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Ruijue Cao
- Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Danni Wu
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Huicong Zhang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Fan Yang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Linhong Wang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
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A Simplified and Effective Approach for the Isolation of Small Pluripotent Stem Cells Derived from Human Peripheral Blood. Biomedicines 2023; 11:biomedicines11030787. [PMID: 36979766 PMCID: PMC10045871 DOI: 10.3390/biomedicines11030787] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 02/24/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023] Open
Abstract
Pluripotent stem cells are key players in regenerative medicine. Embryonic pluripotent stem cells, despite their significant advantages, are associated with limitations such as their inadequate availability and the ethical dilemmas in their isolation and clinical use. The discovery of very small embryonic-like (VSEL) stem cells addressed the aforementioned limitations, but their isolation technique remains a challenge due to their small cell size and their efficiency in isolation. Here, we report a simplified and effective approach for the isolation of small pluripotent stem cells derived from human peripheral blood. Our approach results in a high yield of small blood stem cell (SBSC) population, which expresses pluripotent embryonic markers (e.g., Nanog, SSEA-3) and the Yamanaka factors. Further, a fraction of SBSCs also co-express hematopoietic markers (e.g., CD45 and CD90) and/or mesenchymal markers (e.g., CD29, CD105 and PTH1R), suggesting a mixed stem cell population. Finally, quantitative proteomic profiling reveals that SBSCs contain various stem cell markers (CD9, ITGA6, MAPK1, MTHFD1, STAT3, HSPB1, HSPA4), and Transcription reg complex factors (e.g., STAT5B, PDLIM1, ANXA2, ATF6, CAMK1). In conclusion, we present a novel, simplified and effective isolating process that yields an abundant population of small-sized cells with characteristics of pluripotency from human peripheral blood.
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Liu C, Sharpe P, Volponi AA. Applications of regenerative techniques in adult orthodontics. FRONTIERS IN DENTAL MEDICINE 2023. [DOI: 10.3389/fdmed.2022.1100548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Management of the growing adult orthodontic patient population must contend with challenges particular to orthodontic treatment in adults. These include a limited rate of tooth movement, increased incidence of periodontal complications, higher risk of iatrogenic root resorption and pulp devitalisation, resorbed edentulous ridges, and lack of growth potential. The field of regenerative dentistry has evolved numerous methods of manipulating cellular and molecular processes to rebuild functional oral and dental tissues, and research continues to advance our understanding of stem cells, signalling factors that stimulate repair and extracellular scaffold interactions for the purposes of tissue engineering. We discuss recent findings in the literature to synthesise our understanding of current and prospective approaches based on biological repair that have the potential to improve orthodontic treatment outcomes in adult patients. Methods such as mesenchymal stem cell transplantation, biomimetic scaffold manipulation, and growth factor control may be employed to overcome the challenges described above, thereby reducing adverse sequelae and improving orthodontic treatment outcomes in adult patients. The overarching goal of such research is to eventually translate these regenerative techniques into clinical practice, and establish a new gold standard of safe, effective, autologous therapies.
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Yi Y, Liu Y, Men Y, Wang J, Zhao H. Advances in periodontal stem cells and the regulating niche: From in vitro to in vivo. Genesis 2022; 60:e23494. [PMID: 35894656 DOI: 10.1002/dvg.23494] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 06/20/2022] [Accepted: 07/06/2022] [Indexed: 02/05/2023]
Abstract
Periodontium possesses stem cell populations for its self-maintenance and regeneration, and has been proved to be an optimal stem cell source for tissue engineering. In vitro studies have shown that stem cells can be isolated from periodontal ligament, alveolar bone marrow and gingiva. In recent years, more studies have focused on identification of periodontal stem cells in vivo. Multiple genetic markers, including Gli1, Prx1, Axin2, αSMA, and LepR, were identified with the lineage tracing approaches. Characteristics, functions, and regulatory mechanisms of specific populations expressing one of these markers have been investigated. In vivo studies also revealed that periodontal stem cells can be regulafrted by different niche and mechanisms including intercellular interactions, ECM and multiple secreted factors. In this review, we summarized the current knowledge of in vitro characteristics and in vivo markers of periodontal stem cells, and discussed the specific regulating niche.
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Affiliation(s)
- Yating Yi
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.,Chinese Institute for Brain Research, Beijing, China
| | - Yinghong Liu
- Jinjiang Dental Clinic, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Yi Men
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Jun Wang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Hu Zhao
- Chinese Institute for Brain Research, Beijing, China
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Behm C, Zhao Z, Andrukhov O. Immunomodulatory Activities of Periodontal Ligament Stem Cells in Orthodontic Forces-Induced Inflammatory Processes: Current Views and Future Perspectives. FRONTIERS IN ORAL HEALTH 2022; 3:877348. [PMID: 35601817 PMCID: PMC9114308 DOI: 10.3389/froh.2022.877348] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 04/13/2022] [Indexed: 12/25/2022] Open
Abstract
Orthodontic tooth movement (OTM) is induced by applying active mechanical forces, causing a local non-infectious inflammatory response in the periodontal ligament (PDL). As a prerequisite for OTM, the inflammation status is associated with increased levels of various cytokines and involves the interaction between immune cells and periodontal ligament stem cells (hPDLSCs). It is well established that hPDLSCs respond to orthodontic forces in several ways, such as by secreting multiple inflammatory factors. Another essential feature of hPDLSCs is their immunomodulatory activities, which are executed through cytokine (e.g., TNF-α and IL-1β)-induced production of various soluble immunomediators (e.g., indoleamine-2,3-dioxygenase-1, tumor necrosis factor-inducible gene 6 protein, prostaglandin E2) and direct cell-to-cell contact (e.g., programmed cell death ligand 1, programmed cell death ligand 2). It is well known that these immunomodulatory abilities are essential for local periodontal tissue homeostasis and regeneration. So far, only a handful of studies provides first hints that hPDLSCs change immunological processes during OTM via their immunomodulatory activities. These studies demonstrate the pro-inflammatory aspect of immunomodulation by hPDLSCs. However, no studies exist which investigate cytokine and cell-to-cell contact mediated immunomodulatory activities of hPDLSCs. In this perspective article, we will discuss the potential role of the immunomodulatory potential of hPDLSCs in establishing and resolving the OTM-associated non-infectious inflammation and hence its potential impact on periodontal tissue homeostasis during OTM.
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Affiliation(s)
- Christian Behm
- Competence Center Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
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Okić-Đorđević I, Obradović H, Kukolj T, Petrović A, Mojsilović S, Bugarski D, Jauković A. Dental mesenchymal stromal/stem cells in different microenvironments— implications in regenerative therapy. World J Stem Cells 2021; 13:1863-1880. [PMID: 35069987 PMCID: PMC8727232 DOI: 10.4252/wjsc.v13.i12.1863] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/15/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Current research data reveal microenvironment as a significant modifier of physical functions, pathologic changes, as well as the therapeutic effects of stem cells. When comparing regeneration potential of various stem cell types used for cytotherapy and tissue engineering, mesenchymal stem cells (MSCs) are currently the most attractive cell source for bone and tooth regeneration due to their differentiation and immunomodulatory potential and lack of ethical issues associated with their use. The microenvironment of donors and recipients selected in cytotherapy plays a crucial role in regenerative potential of transplanted MSCs, indicating interactions of cells with their microenvironment indispensable in MSC-mediated bone and dental regeneration. Since a variety of MSC populations have been procured from different parts of the tooth and tooth-supporting tissues, MSCs of dental origin and their achievements in capacity to reconstitute various dental tissues have gained attention of many research groups over the years. This review discusses recent advances in comparative analyses of dental MSC regeneration potential with regards to their tissue origin and specific microenvironmental conditions, giving additional insight into the current clinical application of these cells.
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Affiliation(s)
- Ivana Okić-Đorđević
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Hristina Obradović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Tamara Kukolj
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Anđelija Petrović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Slavko Mojsilović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Diana Bugarski
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Aleksandra Jauković
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
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Pagella P, de Vargas Roditi L, Stadlinger B, Moor AE, Mitsiadis TA. A single-cell atlas of human teeth. iScience 2021; 24:102405. [PMID: 33997688 PMCID: PMC8099559 DOI: 10.1016/j.isci.2021.102405] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/29/2021] [Accepted: 04/06/2021] [Indexed: 12/31/2022] Open
Abstract
Teeth exert fundamental functions related to mastication and speech. Despite their great biomedical importance, an overall picture of their cellular and molecular composition is still missing. In this study, we have mapped the transcriptional landscape of the various cell populations that compose human teeth at single-cell resolution, and we analyzed in deeper detail their stem cell populations and their microenvironment. Our study identified great cellular heterogeneity in the dental pulp and the periodontium. Unexpectedly, we found that the molecular signatures of the stem cell populations were very similar, while their respective microenvironments strongly diverged. Our findings suggest that the microenvironmental specificity is a potential source for functional differences between highly similar stem cells located in the various tooth compartments and open new perspectives toward cell-based dental therapeutic approaches.
Dental atlas of the pulp and periodontal tissues of human teeth Identification of three common MSC subclusters between dental pulp and periodontium Dental pulp and periodontal MSCs are similar, and their niches diverge
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Affiliation(s)
- Pierfrancesco Pagella
- Orofacial Development and Regeneration, Faculty of Medicine, Institute of Oral Biology, Center of Dental Medicine, University of Zurich, Plattenstrasse 11, 8032 Zurich, Switzerland
| | | | - Bernd Stadlinger
- Clinic of Cranio-Maxillofacial and Oral Surgery, University of Zurich, Zurich, Switzerland
| | - Andreas E. Moor
- Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
- Corresponding author
| | - Thimios A. Mitsiadis
- Orofacial Development and Regeneration, Faculty of Medicine, Institute of Oral Biology, Center of Dental Medicine, University of Zurich, Plattenstrasse 11, 8032 Zurich, Switzerland
- Corresponding author
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14
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Zha K, Li X, Yang Z, Tian G, Sun Z, Sui X, Dai Y, Liu S, Guo Q. Heterogeneity of mesenchymal stem cells in cartilage regeneration: from characterization to application. NPJ Regen Med 2021; 6:14. [PMID: 33741999 PMCID: PMC7979687 DOI: 10.1038/s41536-021-00122-6] [Citation(s) in RCA: 107] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 02/01/2021] [Indexed: 01/31/2023] Open
Abstract
Articular cartilage is susceptible to damage but hard to self-repair due to its avascular nature. Traditional treatment methods are not able to produce satisfactory effects. Mesenchymal stem cells (MSCs) have shown great promise in cartilage repair. However, the therapeutic effect of MSCs is often unstable partly due to their heterogeneity. Understanding the heterogeneity of MSCs and the potential of different types of MSCs for cartilage regeneration will facilitate the selection of superior MSCs for treating cartilage damage. This review provides an overview of the heterogeneity of MSCs at the donor, tissue source and cell immunophenotype levels, including their cytological properties, such as their ability for proliferation, chondrogenic differentiation and immunoregulation, as well as their current applications in cartilage regeneration. This information will improve the precision of MSC-based therapeutic strategies, thus maximizing the efficiency of articular cartilage repair.
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Affiliation(s)
- Kangkang Zha
- Medical School of Chinese PLA, Beijing, China
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
| | - Xu Li
- Musculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Zhen Yang
- Medical School of Chinese PLA, Beijing, China
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
| | - Guangzhao Tian
- Medical School of Chinese PLA, Beijing, China
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
| | - Zhiqiang Sun
- Medical School of Chinese PLA, Beijing, China
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
| | - Xiang Sui
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China
| | - Yongjing Dai
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China
| | - Shuyun Liu
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China.
| | - Quanyi Guo
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China.
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15
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Hakki SS, Bozkurt BS, Hakki EE, Karaoz E, Unlu A, Kayis SA. SDF-1 modulates periodontal ligament-Mesenchymal Stem Cells (pdl-MSCs). J Periodontal Res 2021; 56:774-781. [PMID: 33733508 DOI: 10.1111/jre.12876] [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: 10/19/2020] [Revised: 02/21/2021] [Accepted: 02/26/2021] [Indexed: 12/01/2022]
Abstract
BACKGROUND/OBJECTIVES In this in vitro study, the effects of Stromal cell-derived factor-1 (SDF-1) was evaluated on the periodontal ligament-Mesenchymal Stem Cells (pdl-MSCs) functions. MATERIAL AND METHODS Real-time cell analyzer-single plate (RTCA-SP) was employed for proliferation, and RTCA-dual purpose (DP) was utilized for pdl-MSCs migration potential treated with different SDF-1 concentrations (0, 0.1, 1, 10, 100, 200, and 400 ng/ml). Based on the dose-response findings, 10 ng/ml SDF-1 was used for further mRNA experiments. RNAs isolated at 6 and 24 h were checked using quantitative RT-PCR for mineralized tissue-associated genes including type I collagen (COL I), osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor 2 (Runx2). cRNA was synthesized for 6 h, and whole-genome array analysis was performed for over 47.000 probes. Data were subjected to quantile normalization before analysis. RESULTS Increased proliferation and migration were observed in pdl-MSCs treated with 0.1, 1, and 10 ng/ml SDF-1. Increased COL I was observed at both time points: 6 and 24 h. While there was no significant change for OCN, OPN, and Runx2 at 6 h, SDF-1 up-regulated OCN and OPN, but down-regulated Runx2 mRNA expressions at 24 h. IL-8 and ESM1 genes were differentially expressed over twofold when the pdl-MSCs were exposed to SDF-1 at whole-genome array analysis. IL-8 induction was confirmed with RT-PCR. CONCLUSION Findings of this study displayed that SDF-1 modulated pdl-MSCs which were important for periodontal regeneration, inducing migration and proliferation, and regulating extracellular matrix synthesis in favor of the formation of new attachment.
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Affiliation(s)
- Sema S Hakki
- Faculty of Dentistry, Department of Periodontology, Selcuk University, Konya, Turkey.,Research Center of Dental Faculty, Selcuk University, Konya, Turkey
| | - Buket S Bozkurt
- Research Center of Dental Faculty, Selcuk University, Konya, Turkey.,Faculty of Dentistry, Research Lab of Faculty of Dentistry, Hacettepe University, Ankara, Turkey
| | - Erdogan E Hakki
- Faculty of Agriculture, Department of Soil Science and Plant Nutrition, Molecular Genetics & Biotechnology Laboratories Konya, Selcuk University, Konya, Turkey
| | - Erdal Karaoz
- Faculty of Medicine, Department of Histology & Embryology, Istinye University, İstanbul, Turkey.,Center for Stem Cell and Tissue Engineering Research & Practice, Istinye University, İstanbul, Turkey.,Center for Regenerative Medicine and Stem Cell Manufacturing (LivMedCell), Liv Hospital, İstanbul, Turkey
| | - Ali Unlu
- Faculty of Medicine, Department of Biochemistry, Selcuk University, Konya, Turkey
| | - Seyit Ali Kayis
- Faculty of Medicine, Department of Biostatistics, Bolu Abant İzzet Baysal University, Bolu, Turkey
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16
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Dynamic proteomic profiling of human periodontal ligament stem cells during osteogenic differentiation. Stem Cell Res Ther 2021; 12:98. [PMID: 33536073 PMCID: PMC7860046 DOI: 10.1186/s13287-020-02123-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 12/25/2020] [Indexed: 01/07/2023] Open
Abstract
Background Human periodontal ligament stem cells (hPDLSCs) are ideal seed cells for periodontal regeneration. A greater understanding of the dynamic protein profiles during osteogenic differentiation contributed to the improvement of periodontal regeneration tissue engineering. Methods Tandem Mass Tag quantitative proteomics was utilized to reveal the temporal protein expression pattern during osteogenic differentiation of hPDLSCs on days 0, 3, 7 and 14. Differentially expressed proteins (DEPs) were clustered and functional annotated by Gene Ontology (GO) terms. Pathway enrichment analysis was performed based on the Kyoto Encyclopedia of Genes and Genomes database, followed by the predicted activation using Ingenuity Pathway Analysis software. Interaction networks of redox-sensitive signalling pathways and oxidative phosphorylation (OXPHOS) were conducted and the hub protein SOD2 was validated with western blotting. Results A total of 1024 DEPs were identified and clustered in 5 distinctive clusters representing dynamic tendencies. The GO enrichment results indicated that proteins with different tendencies show different functions. Pathway enrichment analysis found that OXPHOS was significantly involved, which further predicted continuous activation. Redox-sensitive signalling pathways with dynamic activation status showed associations with OXPHOS to various degrees, especially the sirtuin signalling pathway. SOD2, an important component of the sirtuin pathway, displays a persistent increase during osteogenesis. Data are available via ProteomeXchange with identifier PXD020908. Conclusion This is the first in-depth dynamic proteomic analysis of osteogenic differentiation of hPDLSCs. It demonstrated a dynamic regulatory mechanism of hPDLSC osteogenesis and might provide a new perspective for research on periodontal regeneration. Graphical abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s13287-020-02123-6.
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Berbéri A, Sabbagh J, Bou Assaf R, Ghassibe-Sabbagh M, Al-Nemer F, El Majzoub R, Fayyad-Kazan M, Badran B. Comparing the osteogenic potential of schneiderian membrane and dental pulp mesenchymal stem cells: an in vitro study. Cell Tissue Bank 2021; 22:409-417. [PMID: 33386464 DOI: 10.1007/s10561-020-09887-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 12/04/2020] [Indexed: 10/22/2022]
Abstract
Mesenchymal stem cells, being characterized by high self-renewal capacity and multi-lineage differentiation potential, are widely used in regenerative medicine especially for repair of bone defects in patients with poor bone regenerative capacity. In this study, we aimed to compare the osteogenic potential of human maxillary schneiderian sinus membrane (hMSSM)-derived stem cells versus permanent teeth dental pulp stem cells (DPSCs). Both cells types were cultivated in osteogenic and non-osteogenic inductive media. Alkaline phosphatase (ALP) activity assay and quantitative real-time PCR analysis were carried out to assess osteogenic differentiation. We showed that ALP activity and osteoblastic markers transcription levels were more striking in hMSSM-derived stem cells than DPSCs. Our results highlight hMSSM-derived stem cells as a recommended stem cell type for usage during bone tissue regenerative therapy.
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Affiliation(s)
- Antoine Berbéri
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Lebanese University, Rafic Hariri Campus, POBox 5208-116, Beirut, Lebanon.
| | - Joseph Sabbagh
- Department of Restorative Dentistry and Endodontics, Faculty of Dental Medicine, Lebanese University, Beirut, Lebanon
| | - Rita Bou Assaf
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Lebanese University, Rafic Hariri Campus, POBox 5208-116, Beirut, Lebanon
| | - Michella Ghassibe-Sabbagh
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon
| | - Fatima Al-Nemer
- Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath, Beirut, Lebanon
| | - Rania El Majzoub
- School of Pharmacy (Department of Biomedical Sciences), Lebanese International University, Mazraa, 146404, Lebanon
| | - Mohammad Fayyad-Kazan
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon. .,Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath, Beirut, Lebanon.
| | - Bassam Badran
- Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath, Beirut, Lebanon
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18
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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.
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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
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19
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Lin YS, Wang FZ, Lei XJ, He JM. [Comparative study with the effect of stromal cell derived factor-1 on osteogenic differentiation of human healthy and inflammatory periodontal ligament stem cells]. HUA XI KOU QIANG YI XUE ZA ZHI = HUAXI KOUQIANG YIXUE ZAZHI = WEST CHINA JOURNAL OF STOMATOLOGY 2019; 37:469-475. [PMID: 31721491 DOI: 10.7518/hxkq.2019.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
OBJECTIVE This study aims to compare the osteogenic differentiation capability of stem cells derived from human inflammatory periodontal ligament tissues (iPDLSCs) with those of stem cells derived from healthy periodontal ligament tissues (hPDLSCs). Both types of tissues were induced by stromal cell derived factor (SDF-1) in vitro. METHODS iPDLSCs and hPDLSCs were primarily cultured by tissue digestion method and purified by limited dilution cloning. The cells were passaged and identified by stem cell surface marker expression through flow cytometry. Then, we used thiazolyl blue tetrazolium bromide to detect and compare the proliferation capabilities of the iPDLSCs and hPDLSCs. Express of bone volumes were detected by alizarin red staining after SDF-1 was added to the cells. Using alkaline phosphatase, we evaluated the osteogenic differentiation capability of the cells induced by SDF-1. The expression levels of the osteogenesis-related genes of the cells induced by SDF-1 were determined by reverse transcription-polymerase chain reaction. RESULTS After purification, both iPDLSCs and hPDLSCs expressed stem cell markers. hPDLCSs had a higher proliferation capability than iPDLSCs. Osteogenesis-related genes had higher expression levels in the cells induced by SDF-1 than in those without induction (P<0.05). SDF-1 at 50 and 200 ng·mL⁻¹ concentration greatly affected the differen-tiation capabilities of iPDLSCs and hPDLSCs respectively. CONCLUSIONS iPDLSCs and hPDLSCs had osteogenic differentia-tion capability. The level of osteogenic differentiation in normal and inflamed periodontal ligament stem cells increases after SDF-1 induction.
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Affiliation(s)
- Yong-Sheng Lin
- Key Laboratory of Oral Diseases of Gansu Provincial, Key Laboratory of Stomatology of State Ethnic Affairs Commission, Northwest Minzu University, Lanzhou 730030, China
| | - Feng-Zhi Wang
- Dept. of Oral Medicine, Hainan Stomatological Hospital, Hainan 570100, China
| | - Xiao-Jing Lei
- Dept. of Oral Medicine, Hainan Stomatological Hospital, Hainan 570100, China
| | - Jian-Min He
- Dept. of Stomatology, Gansu Provincial Hospital, Lanzhou 730000, China
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20
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Winning L, El Karim IA, Lundy FT. A Comparative Analysis of the Osteogenic Potential of Dental Mesenchymal Stem Cells. Stem Cells Dev 2019; 28:1050-1058. [DOI: 10.1089/scd.2019.0023] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Affiliation(s)
- Lewis Winning
- The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland
| | - Ikhlas A. El Karim
- The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland
| | - Fionnuala T. Lundy
- The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland
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21
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Head to Knee: Cranial Neural Crest-Derived Cells as Promising Candidates for Human Cartilage Repair. Stem Cells Int 2019; 2019:9310318. [PMID: 30766608 PMCID: PMC6350557 DOI: 10.1155/2019/9310318] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 11/04/2018] [Accepted: 12/06/2018] [Indexed: 12/13/2022] Open
Abstract
A large array of therapeutic procedures is available to treat cartilage disorders caused by trauma or inflammatory disease. Most are invasive and may result in treatment failure or development of osteoarthritis due to extensive cartilage damage from repeated surgery. Despite encouraging results of early cell therapy trials that used chondrocytes collected during arthroscopic surgery, these approaches have serious disadvantages, including morbidity associated with cell harvesting and low predictive clinical outcomes. To overcome these limitations, adult stem cells derived from bone marrow and subsequently from other tissues are now considered as preferred sources of cells for cartilage regeneration. Moreover, with new evidence showing that the choice of cell source is one of the most important factors for successful cell therapy, there is growing interest in neural crest-derived cells in both the research and clinical communities. Neural crest-derived cells such as nasal chondrocytes and oral stem cells that exhibit chondrocyte-like properties seem particularly promising in cartilage repair. Here, we review the types of cells currently available for cartilage cell therapy, including articular chondrocytes and various mesenchymal stem cells, and then highlight recent developments in the use of neural crest-derived chondrocytes and oral stem cells for repair of cartilage lesions.
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22
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Kukolj T, Trivanović D, Mojsilović S, Okić Djordjević I, Obradović H, Krstić J, Jauković A, Bugarski D. IL-33 guides osteogenesis and increases proliferation and pluripotency marker expression in dental stem cells. Cell Prolif 2018; 52:e12533. [PMID: 30430681 PMCID: PMC6430470 DOI: 10.1111/cpr.12533] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 08/03/2018] [Accepted: 08/28/2018] [Indexed: 12/12/2022] Open
Abstract
Objectives Soluble IL‐33 (interleukin (IL)‐1‐like cytokine) acts as endogenous alarm signal (alarmin). Since alarmins, besides activating immune system, act to restore tissue homeostasis, we investigated whether IL‐33 exerts beneficial effects on oral stem cell pull. Materials and Methods Clonogenicity, proliferation, differentiation and senescence of stem cells derived from human periodontal ligament (PDLSCs) and dental pulp (DPSCs) were determined after in vitro exposure to IL‐33. Cellular changes were detected by flow cytometry, Western blot, immunocytochemistry and semiquantitative RT‐PCR. Results IL‐33 stimulated proliferation, clonogenicity and expression of pluripotency markers, OCT‐4, SOX‐2 and NANOG, but it inhibited ALP activity and mineralization in both PDLSCs and DPSCs. Higher Ki67 expression and reduced β‐galactosidase activity in IL‐33‐treated cells were demonstrated, whereas these trends were more conspicuous in osteogenic medium. However, after 7‐day IL‐33 pretreatment, differentiation capacity of IL‐33‐pretreated cells was retained, and increased ALP activity was observed in both cell types. Results showed that IL‐33 regulates NF‐κB and β‐catenin signalling, indicating the association of these molecules with changes observed in IL‐33‐treated PDLSCs and DPSCs, particularly their proliferation, pluripotency‐associated marker expression and osteogenesis. Conclusions IL‐33 treatment impairs osteogenesis of PDLSCs and DPSCs, while increases their clonogenicity, proliferation and pluripotency marker expression. After exposure to IL‐33, osteogenic capacity of cells stayed intact. NF‐κB and β‐catenin are implicated in the effects achieved by IL‐33 in PDLSCs and DPSCs.
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Affiliation(s)
- Tamara Kukolj
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Drenka Trivanović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Slavko Mojsilović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Ivana Okić Djordjević
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Hristina Obradović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Jelena Krstić
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Jauković
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Diana Bugarski
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
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23
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Li G, Han N, Zhang X, Yang H, Cao Y, Wang S, Fan Z. Local Injection of Allogeneic Stem Cells from Apical Papilla Enhanced Periodontal Tissue Regeneration in Minipig Model of Periodontitis. BIOMED RESEARCH INTERNATIONAL 2018; 2018:3960798. [PMID: 30112386 PMCID: PMC6077668 DOI: 10.1155/2018/3960798] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 06/03/2018] [Accepted: 06/21/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Discovering suitable seeding cells and simple application technique will be beneficial for MSC-mediated treatment of periodontitis. Stem cells from apical papilla (SCAPs) might be the candidate seeding cell for the periodontal tissues regeneration based on their origin and characters. In this research, we investigated the effect of SCAPs on periodontal tissue regeneration in swine by local injection. METHODS We established experimental periodontitis model in miniature pigs and then treated them with SCAPs by local injection. Clinical assessments, computed tomography (CT) scanning, histologic examination, and quantitative measurements were used to evaluate the effect of periodontal tissues regeneration. RESULTS At 12 weeks after injection, clinical assessments showed that probing depth, gingival recession, and attachment loss values were 5.44±0.77 mm versus 7.33±1.0 mm (p<0.01), 2.33±0.33 mm versus 2.11±0.69 mm (p>0.05), and 7.78±0.84 mm versus 9.44±1.07 mm (p<0.01) in SCAPs group and 0.9% NaCl group, respectively. CT scan results showed a significant increase of 12.86 mm3 alveolar bone regeneration in SCAPs group compared with 0.9% NaCl group. In addition, histopathology results demonstrated remarkable regeneration in SCAPs group, whereas regeneration of periodontal tissue was hardly found in 0.9% NaCl group. CONCLUSION Local injection of SCAPs could effectively restore tissue defects brought about by periodontitis in the swine model. Thus, SCAPs, as an easily accessible dental-deriving stem cell, may serve as an alternative application for periodontitis treatment.
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Affiliation(s)
- Guoqing Li
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China
- Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China
| | - Nannan Han
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China
- Department of Periodontology, Capital Medical University School of Stomatology, Beijing 100050, China
| | - Xiuli Zhang
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China
- Department of Periodontology, Capital Medical University School of Stomatology, Beijing 100050, China
| | - Haoqing Yang
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China
| | - Yangyang Cao
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China
| | - Songlin Wang
- Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China
- Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, No.10 Xitoutiao Youanmen, Fengtai District, Beijing 100069, China
| | - Zhipeng Fan
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, No. 4 Tiantanxili, Dongcheng District, Beijing 100050, China
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A High-Resolution Proteomic Landscaping of Primary Human Dental Stem Cells: Identification of SHED- and PDLSC-Specific Biomarkers. Int J Mol Sci 2018; 19:ijms19010158. [PMID: 29304003 PMCID: PMC5796107 DOI: 10.3390/ijms19010158] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 12/25/2017] [Accepted: 12/29/2017] [Indexed: 02/06/2023] Open
Abstract
Dental stem cells (DSCs) have emerged as a promising tool for basic research and clinical practice. A variety of adult stem cell (ASC) populations can be isolated from different areas within the dental tissue, which, due to their cellular and molecular characteristics, could give rise to different outcomes when used in potential applications. In this study, we performed a high-throughput molecular comparison of two primary human adult dental stem cell (hADSC) sub-populations: Stem Cells from Human Exfoliated Deciduous Teeth (SHEDs) and Periodontal Ligament Stem Cells (PDLSCs). A detailed proteomic mapping of SHEDs and PDLSCs, via employment of nano-LC tandem-mass spectrometry (MS/MS) revealed 2032 identified proteins in SHEDs and 3235 in PDLSCs. In total, 1516 proteins were expressed in both populations, while 517 were unique for SHEDs and 1721 were exclusively expressed in PDLSCs. Further analysis of the recorded proteins suggested that SHEDs predominantly expressed molecules that are involved in organizing the cytoskeletal network, cellular migration and adhesion, whereas PDLSCs are highly energy-producing cells, vastly expressing proteins that are implicated in various aspects of cell metabolism and proliferation. Applying the Rho-GDI signaling pathway as a paradigm, we propose potential biomarkers for SHEDs and for PDLSCs, reflecting their unique features, properties and engaged molecular pathways.
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Khoshhal M, Amiri I, Gholami L. Comparison of in vitro properties of periodontal ligament stem cells derived from permanent and deciduous teeth. J Dent Res Dent Clin Dent Prospects 2017; 11:140-148. [PMID: 29184628 PMCID: PMC5666212 DOI: 10.15171/joddd.2017.026] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Accepted: 07/29/2017] [Indexed: 12/15/2022] Open
Abstract
Background. Stem cells have contributed to the development of tissue-engineered-based regenerative periodontal therapies. In order to find the best stem cell sources for such therapies, the biologic properties of stem cells isolated from periodontal ligaments (PDL) of deciduous (DePDLSC) and permanent (PePDLSC) teeth were comparatively evaluated. Methods. PDL stem cells were isolated from six sound fully erupted premolars and six deciduous canines of healthy subjects. In vitro biologic characteristics such as colony formation, viability, stem cell marker identification and osteogenic differentiation (using alkaline phosphatase analysis and Alizarin red staining) were comparatively assessed using one-way ANOVA and post hoc Tukey tests using SPSS 13.0. Results. Stem cell populations isolated from both groups were CD105+ and CD90+ and CD45‒. No statistically significant differences were found in stem cell markers, colony formation and viability. Both groups were capable of osteogenic differentiation. However, alkaline phosphatase activity test showed a statistically significant difference, with PePDLSC exhibiting higher alkaline phosphatase activity (P=0.000). No statistically significant difference was seen in quantitative alizarine red staining (P=0.559). Conclusion. Mesenchymal stem cells of PDL could successfully be isolated from permanent and deciduous teeth. A minor difference was observed in the osteogenic properties of the two cell types, which might affect their future clinical applications.
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Affiliation(s)
- Masoumeh Khoshhal
- Dental Implant Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Iraj Amiri
- Department of Anatomy and Embryology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Leila Gholami
- Department of Periodontology, Faculty of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran
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Otero L, Carrillo N, Calvo-Guirado J, Villamil J, Delgado-Ruíz R. Osteogenic potential of platelet-rich plasma in dental stem-cell cultures. Br J Oral Maxillofac Surg 2017. [DOI: 10.1016/j.bjoms.2017.05.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Manokawinchoke J, Nattasit P, Thongngam T, Pavasant P, Tompkins KA, Egusa H, Osathanon T. Indirect immobilized Jagged1 suppresses cell cycle progression and induces odonto/osteogenic differentiation in human dental pulp cells. Sci Rep 2017; 7:10124. [PMID: 28860516 PMCID: PMC5578993 DOI: 10.1038/s41598-017-10638-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 08/14/2017] [Indexed: 12/22/2022] Open
Abstract
Notch signaling regulates diverse biological processes in dental pulp tissue. The present study investigated the response of human dental pulp cells (hDPs) to the indirect immobilized Notch ligand Jagged1 in vitro. The indirect immobilized Jagged1 effectively activated Notch signaling in hDPs as confirmed by the upregulation of HES1 and HEY1 expression. Differential gene expression profiling using an RNA sequencing technique revealed that the indirect immobilized Jagged1 upregulated genes were mainly involved in extracellular matrix organization, disease, and signal transduction. Downregulated genes predominantly participated in the cell cycle, DNA replication, and DNA repair. Indirect immobilized Jagged1 significantly reduced cell proliferation, colony forming unit ability, and the number of cells in S phase. Jagged1 treated hDPs exhibited significantly higher ALP enzymatic activity, osteogenic marker gene expression, and mineralization compared with control. Pretreatment with a γ-secretase inhibitor attenuated the Jagged1-induced ALP activity and mineral deposition. NOTCH2 shRNA reduced the Jagged1-induced osteogenic marker gene expression, ALP enzymatic activity, and mineral deposition. In conclusion, indirect immobilized Jagged1 suppresses cell cycle progression and induces the odonto/osteogenic differentiation of hDPs via the canonical Notch signaling pathway.
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Affiliation(s)
- Jeeranan Manokawinchoke
- Excellence Center in Regenerative Dentistry, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
- Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Praphawi Nattasit
- Excellence Center in Regenerative Dentistry, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Tanutchaporn Thongngam
- Excellence Center in Regenerative Dentistry, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Prasit Pavasant
- Excellence Center in Regenerative Dentistry, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
- Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Kevin A Tompkins
- Office of Research Affairs, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Hiroshi Egusa
- Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, 980-8575, Japan
| | - Thanaphum Osathanon
- Excellence Center in Regenerative Dentistry, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand.
- Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand.
- Craniofacial Genetics and Stem Cells Research Group, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand.
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Pettersson LF, Kingham PJ, Wiberg M, Kelk P. In Vitro Osteogenic Differentiation of Human Mesenchymal Stem Cells from Jawbone Compared with Dental Tissue. Tissue Eng Regen Med 2017; 14:763-774. [PMID: 30603526 PMCID: PMC6171664 DOI: 10.1007/s13770-017-0071-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 07/07/2017] [Accepted: 07/11/2017] [Indexed: 12/26/2022] Open
Abstract
Autologous bone transplantation is the current gold standard for reconstruction of jawbone defects. Bone regeneration using mesenchymal stem cells (MSC) is an interesting alternative to improve the current techniques, which necessitate a second site of surgery resulting in donor site morbidity. In this study, we compared the osteogenic ability of jawbone MSC (JB-MSC) with MSC from tissues with neural crest origin, namely, the dental pulp, apical papilla and periodontal ligament. All four types of MSC were isolated from the same patient (n = 3 donors) to exclude inter-individual variations. The MSC growth and differentiation properties were characterized. The osteogenic differentiation potential in each group of cells was assessed quantitatively to determine if there were any differences between the cell types. All cells expressed the MSC-associated surface markers CD73, CD90, CD105, and CD146 and were negative for CD11b, CD19, CD34, CD45 and HLA-DR. All cell types proliferated at similar rates, exhibited similar clonogenic activity and could differentiate into adipocytes and osteoblasts. An alkaline phosphatase assay, OsteoImage™ assay for mineralization and qRT-PCR measuring the genes runx2, ALP and OCN, indicated that there were no significant differences in the osteogenic differentiation ability between the various MSCs. In conclusion, we show that from a small segment of jawbone it is possible to isolate sufficient quantities of MSC and that these cells can easily be expanded and differentiated into osteoblasts. JB-MSC appear to be good candidates for future bone regeneration applications in the craniofacial region.
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Affiliation(s)
- Linda F Pettersson
- 1Department of Integrative Medical Biology, Section for Anatomy, Umeå University, 90187 Umeå, Sweden.,3Department of Odontology, Section for Oral and Maxillofacial Surgery, Umeå University, 90187 Umeå, Sweden
| | - Paul J Kingham
- 1Department of Integrative Medical Biology, Section for Anatomy, Umeå University, 90187 Umeå, Sweden
| | - Mikael Wiberg
- 1Department of Integrative Medical Biology, Section for Anatomy, Umeå University, 90187 Umeå, Sweden.,2Department of Surgical and Perioperative Sciences, Section for Hand and Plastic Surgery, Umeå University, 90185 Umeå, Sweden
| | - Peyman Kelk
- 1Department of Integrative Medical Biology, Section for Anatomy, Umeå University, 90187 Umeå, Sweden
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D'Alimonte I, Mastrangelo F, Giuliani P, Pierdomenico L, Marchisio M, Zuccarini M, Di Iorio P, Quaresima R, Caciagli F, Ciccarelli R. Osteogenic Differentiation of Mesenchymal Stromal Cells: A Comparative Analysis Between Human Subcutaneous Adipose Tissue and Dental Pulp. Stem Cells Dev 2017; 26:843-855. [DOI: 10.1089/scd.2016.0190] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Iolanda D'Alimonte
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy
- Department of Aging Research Center and Translational Medicine (CeSI-MeT), University of Chieti-Pescara, Chieti, Italy
- StemTeCh Group, Chieti, Italy
| | - Filiberto Mastrangelo
- Unit of Dentistry, IRCCS San Raffaele Scientific Institute, Vita e Salute University, Milano, Italy
| | - Patricia Giuliani
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy
| | - Laura Pierdomenico
- Department of Medicine and Aging Science, University of Chieti-Pescara, Chieti, Italy
- Department of Aging Research Center and Translational Medicine (CeSI-MeT), University of Chieti-Pescara, Chieti, Italy
- StemTeCh Group, Chieti, Italy
| | - Marco Marchisio
- Department of Medicine and Aging Science, University of Chieti-Pescara, Chieti, Italy
- Department of Aging Research Center and Translational Medicine (CeSI-MeT), University of Chieti-Pescara, Chieti, Italy
- StemTeCh Group, Chieti, Italy
| | - Mariachiara Zuccarini
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy
- Department of Aging Research Center and Translational Medicine (CeSI-MeT), University of Chieti-Pescara, Chieti, Italy
| | - Patrizia Di Iorio
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy
| | - Raimondo Quaresima
- Department of Civil Engineering, Architecture and Environment, University of L'Aquila, L'Aquila, Italy
| | - Francesco Caciagli
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy
| | - Renata Ciccarelli
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy
- Department of Aging Research Center and Translational Medicine (CeSI-MeT), University of Chieti-Pescara, Chieti, Italy
- StemTeCh Group, Chieti, Italy
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Kim BB, Kim M, Park YH, Ko Y, Park JB. Short-term application of dexamethasone on stem cells derived from human gingiva reduces the expression of RUNX2 and β-catenin. J Int Med Res 2017; 45:993-1006. [PMID: 28459354 PMCID: PMC5536397 DOI: 10.1177/0300060517701035] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Accepted: 03/01/2017] [Indexed: 12/21/2022] Open
Abstract
Objective Next-generation sequencing was performed to evaluate the effects of short-term application of dexamethasone on human gingiva-derived mesenchymal stem cells. Methods Human gingiva-derived stem cells were treated with a final concentration of 10-7 M dexamethasone and the same concentration of vehicle control. This was followed by mRNA sequencing and data analysis, gene ontology and pathway analysis, quantitative real-time polymerase chain reaction of mRNA, and western blot analysis of RUNX2 and β-catenin. Results In total, 26,364 mRNAs were differentially expressed. Comparison of the results of dexamethasone versus control at 2 hours revealed that 7 mRNAs were upregulated and 25 mRNAs were downregulated. The application of dexamethasone reduced the expression of RUNX2 and β-catenin in human gingiva-derived mesenchymal stem cells. Conclusion The effects of dexamethasone on stem cells were evaluated with mRNA sequencing, and validation of the expression was performed with qualitative real-time polymerase chain reaction and western blot analysis. The results of this study can provide new insights into the role of mRNA sequencing in maxillofacial areas.
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Affiliation(s)
- Bo-Bae Kim
- Department of Periodontics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Minji Kim
- Department of Periodontics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | | | - Youngkyung Ko
- Department of Periodontics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jun-Beom Park
- Department of Periodontics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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In vitro proliferation and osteogenic differentiation of endometrial stem cells and dental pulp stem cells. Cell Tissue Bank 2017; 18:239-247. [PMID: 28364342 DOI: 10.1007/s10561-017-9620-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 03/25/2017] [Indexed: 12/22/2022]
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Variation in human dental pulp stem cell ageing profiles reflect contrasting proliferative and regenerative capabilities. BMC Cell Biol 2017; 18:12. [PMID: 28148303 PMCID: PMC5288874 DOI: 10.1186/s12860-017-0128-x] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2016] [Accepted: 01/20/2017] [Indexed: 12/17/2022] Open
Abstract
Background Dental pulp stem cells (DPSCs) are increasingly being recognized as a viable cell source for regenerative medicine. Although significant variations in their ex vivo expansion are well-established, DPSC proliferative heterogeneity remains poorly understood, despite such characteristics influencing their regenerative and therapeutic potential. This study assessed clonal human DPSC regenerative potential and the impact of cellular senescence on these responses, to better understand DPSC functional behaviour. Results All DPSCs were negative for hTERT. Whilst one DPSC population reached >80 PDs before senescence, other populations only achieved <40 PDs, correlating with DPSCs with high proliferative capacities possessing longer telomeres (18.9 kb) than less proliferative populations (5–13 kb). High proliferative capacity DPSCs exhibited prolonged stem cell marker expression, but lacked CD271. Early-onset senescence, stem cell marker loss and positive CD271 expression in DPSCs with low proliferative capacities were associated with impaired osteogenic and chondrogenic differentiation, favouring adipogenesis. DPSCs with high proliferative capacities only demonstrated impaired differentiation following prolonged expansion (>60 PDs). Conclusions This study has identified that proliferative and regenerative heterogeneity is related to contrasting telomere lengths and CD271 expression between DPSC populations. These characteristics may ultimately be used to selectively screen and isolate high proliferative capacity/multi-potent DPSCs for regenerative medicine exploitation.
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Khurana R, Kudva PB, Husain SY. Comparative evaluation of the isolation and quantification of stem cells derived from dental pulp and periodontal ligament of a permanent tooth and to assess their viability and proliferation on a platelet-rich fibrin scaffold. J Indian Soc Periodontol 2017; 21:16-20. [PMID: 29386795 PMCID: PMC5767982 DOI: 10.4103/jisp.jisp_182_16] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2016] [Accepted: 10/09/2017] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The present study aims to comparatively evaluate the isolation and quantification of stem cells derived from dental pulp and periodontal ligament of a permanent tooth and to assess their viability and proliferation on a platelet-rich fibrin (PRF) scaffold. MATERIALS AND METHODS A total of 15 systemically healthy individuals between the age group of 15-25 years requiring third molar or orthodontic premolar extractions. Teeth were extracted atraumatically and transported to the laboratory. Stem cells were isolated from dental pulp and periodontal ligament. After attaining more than 90% confluency by the 7th day, these cells were tested for their viability and characterization. Stem cells were also incubated with PRF and viability was assessed on the 7th day. RESULTS The mean number of cell for dental pulp stem cells (DPSCs) and periodontal ligament stem cell (PDLSC) was statistically insignificant (P > 0.05). The mean live cell viability was compared between DPSC (98.07%) and PDLSC (98%). Both DPSC and PDLSC showed a high percentage of expression of CD73 markers, 30.40% and 29.80%, respectively. However, DPSCs and PDLSCs lacked expression of CD34 expressing only 3.47% and 3.53%, respectively. PRF membrane as a scaffold exhibited no cytotoxic effects on DPCS's or PDLSC's. The cell viability of cells cultured with PRF was statistically insignificant (P > 0.05) when compared to the cells cultured with culture media. CONCLUSION The study thus indicates that dental pulp and periodontal ligament are both rich sources of mesenchymal stem cells and can be successfully used for obtaining stem cells. PRF exhibits no cytotoxic effects on the cells and can be used in conjunction with dental stem cells.
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Affiliation(s)
- Rohit Khurana
- Department of Periodontology and Implantology, Jaipur Dental College, Jaipur, Rajasthan, India
| | - Praveen Bhasker Kudva
- Department of Periodontology and Implantology, Jaipur Dental College, Jaipur, Rajasthan, India
| | - Syed Yawer Husain
- Department of Dental Materials, RUHS-CDS and Stem Cell Research Lab, SMS Medical College, Jaipur, Rajasthan, India
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Liu L, Peng Z, Huang H, Xu Z, Wei X. Luteolin and apigenin activate the Oct-4/Sox2 signal via NFATc1 in human periodontal ligament cells. Cell Biol Int 2016; 40:1094-106. [PMID: 27449921 DOI: 10.1002/cbin.10648] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Accepted: 07/18/2016] [Indexed: 12/15/2022]
Abstract
Identifying small molecules to activate the Oct-4/Sox2-derived pluripotency network represents a hopeful and safe method to pluripotency without genetic manipulation. Luteolin and apigenin, two major bioactive flavonoids, enhance reprogramming efficiency and increase expression of Oct-4/Sox2/c-Myc, albeit the detailed mechanism regulating pluripotency in dental-derived cells remains unknown. In the present study, to elucidate the effect of luteolin/apigenin on pluripotency of periodontal ligament cells (PDLCs) through interaction with downstream signals, we examined cell cycle, proliferation, apoptosis, expression of Oct-4/Sox2/c-Myc, and multilineage differentiation of PDLCs with luteolin/apigenin treatment. Moreover, we profiled the differentially expressed pluripotency genes by PCR arrays. Our results demonstrated that luteolin/apigenin restrained cell proliferation, increased apoptosis, and arrested PDLCs in G2/M and S phase. Luteolin and apigenin activated expression of Oct-4, Sox2, and c-Myc in a time- and dose-dependent pattern, and repressed lineage-specific differentiation. PCR arrays profiled multiple signals in PDLCs with luteolin/apigenin treatment, among which NFATc1 was the major upregulated gene. Notably, blocking of the NFATc1 signal with INCA-6 significantly decreased mRNA and protein expression of Oct-4, Sox2, and c-Myc in PDLCs with luteolin/apigenin treatment, indicating that NFATc1 may act as an upstream modulator of Oct-4/Sox2 signal. Taken together, this study showed that luteolin and apigenin effectively maintain pluripotency of PDLCs through activation of Oct-4/Sox2 signal via NFATc1.
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Affiliation(s)
- Lu Liu
- Operative Dentistry and Endodontics, Guanghua School of Stomatology, Affiliated Stomatological Hospital, Guangdong Province Key Laboratory of Stomatology, Sun Yat-Sen University, 56 Lingyuan Xi Rd, Guangzhou, 510055, Guangdong, China
| | - Zhengjun Peng
- Operative Dentistry and Endodontics, Guanghua School of Stomatology, Affiliated Stomatological Hospital, Guangdong Province Key Laboratory of Stomatology, Sun Yat-Sen University, 56 Lingyuan Xi Rd, Guangzhou, 510055, Guangdong, China
| | - Haoquan Huang
- Operative Dentistry and Endodontics, Guanghua School of Stomatology, Affiliated Stomatological Hospital, Guangdong Province Key Laboratory of Stomatology, Sun Yat-Sen University, 56 Lingyuan Xi Rd, Guangzhou, 510055, Guangdong, China
| | - Zhezhen Xu
- Operative Dentistry and Endodontics, Guanghua School of Stomatology, Affiliated Stomatological Hospital, Guangdong Province Key Laboratory of Stomatology, Sun Yat-Sen University, 56 Lingyuan Xi Rd, Guangzhou, 510055, Guangdong, China
| | - Xi Wei
- Operative Dentistry and Endodontics, Guanghua School of Stomatology, Affiliated Stomatological Hospital, Guangdong Province Key Laboratory of Stomatology, Sun Yat-Sen University, 56 Lingyuan Xi Rd, Guangzhou, 510055, Guangdong, China.
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Xia Y, Tang HN, Wu RX, Yu Y, Gao LN, Chen FM. Cell Responses to Conditioned Media Produced by Patient-Matched Stem Cells Derived From Healthy and Inflamed Periodontal Ligament Tissues. J Periodontol 2015; 87:e53-63. [PMID: 26609694 DOI: 10.1902/jop.2015.150462] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Periodontal ligament stem cells (PDLSCs) derived from clinically compromised teeth with periodontitis are considered a readily accessible cell source, but their impaired stem cell functionalities, as observed in various in vitro and in vivo models, necessitate further investigation of these inflamed cells before their translation into therapeutic applications. In this study, the effects of conditioned media (CM) produced by stem cells derived from human healthy periodontal ligament tissues (H-PDLSCs) or inflamed periodontal ligament tissues (I-PDLSCs), referred to as H-CM and I-CM, respectively, on the biologic properties of H-PDLSCs and I-PDLSCs from the same donor are compared to explore the extent to which inflamed cells can be rescued by their extrinsic environment (i.e., by H-CM). METHODS H-CM and I-CM were prepared from in vitro cell cultures, and the cellular responses of H-PDLSCs and I-PDLSCs to patient-matched H-CM and I-CM were investigated in terms of colony-forming ability, cell proliferation, and adipogenic/osteogenic differentiation. RESULTS In H-CM and I-CM, H-PDLSCs and I-PDLSCs exhibited similar adipogenic potential. However, when incubated in I-CM, both cell types demonstrated an increased capacity to proliferate but a decreased capacity to differentiate into osteoblasts. Significantly, the impaired osteogenic differentiation of I-PDLSCs was partially rescued by incubation in H-CM under osteo-inducing conditions. CONCLUSION The CM of patient-matched H-PDLSCs and I-PDLSCs differed, and the impaired osteogenic differentiation of inflamed stem cells had the potential to be rescued, at least partially, for therapeutic use via changing the cell culture microenvironment in vitro.
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Affiliation(s)
- Yu Xia
- State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, P. R. China.,Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University
| | - Hao-Ning Tang
- State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, P. R. China.,Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University
| | - Rui-Xin Wu
- State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, P. R. China.,Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University
| | - Yang Yu
- State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, P. R. China.,Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University
| | - Li-Na Gao
- State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, P. R. China.,Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University
| | - Fa-Ming Chen
- State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, P. R. China.,Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University
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Morrison T, McAuley DF, Krasnodembskaya A. Mesenchymal stromal cells for treatment of the acute respiratory distress syndrome: The beginning of the story. J Intensive Care Soc 2015; 16:320-329. [PMID: 28979439 PMCID: PMC5606462 DOI: 10.1177/1751143715586420] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
In spite of decades of research, the acute respiratory distress syndrome (ARDS) continues to have an unacceptably high mortality and morbidity. Mesenchymal stromal cells (MSCs) present a promising candidate for the treatment of this condition and have demonstrated benefit in preclinical models. MSCs, which are a topic of growing interest in many inflammatory disorders, have already progressed to early phase clinical trials in ARDS. While a number of their mechanisms of effect have been elucidated, a better understanding of the complex actions of these cells may pave the way for MSC modifications, which might enable more effective translation into clinical practice.
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Grimm WD, Giesenhagen B, Hakki S, Schau I, Sirak S, Sletov A, Varga G, Vukovic MA, Widera D. Translational Research and Therapeutic Applications of Neural Crest-Derived Stem Cells in Regenerative Periodontology. ACTA ACUST UNITED AC 2015. [DOI: 10.1007/s40496-015-0067-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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