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1
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Su W, Liao C, Liu X. Angiogenic and neurogenic potential of dental-derived stem cells for functional pulp regeneration: A narrative review. Int Endod J 2025; 58:391-410. [PMID: 39660369 DOI: 10.1111/iej.14180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 10/26/2024] [Accepted: 11/22/2024] [Indexed: 12/12/2024]
Abstract
BACKGROUND Dental pulp tissue engineering is expected to become an ideal treatment for irreversible pulpitis and apical periodontitis. However, angiogenesis and neurogenesis for functional pulp regeneration have not yet met the standard for large-scale clinical application, and need further research. OBJECTIVE This review focused on the potential mechanisms of angiogenesis and neurogenesis in pulp regeneration, including stem cell types, upstream and downstream regulatory molecules and cascade signalling pathways, thereby providing a theoretical basis and inspiring new ideas to improve the effectiveness of dental pulp tissue engineering. METHODS An electronic literature search was carried out using the keywords of 'pulp regeneration', 'stem cell transplantation', 'dental pulp stem cells', 'angiogenesis' and 'neurogenesis'. The resulting literature was screened and reviewed. RESULTS Stem cells used in dental pulp tissue engineering can be classified as dental-derived and non-dental-derived stem cells, amongst which dental pulp stem cells (DPSC) have achieved promising results in animal experiments and clinical trials. Multiple molecules and signalling pathways are involved in the process of DPSC-mediated angiogenic and neurogenetic regeneration. In order to promote angiogenesis and neurogenesis in pulp regeneration, feasible measures include the addition of growth factors, the modulation of transcription factors and signalling pathways, the use of extracellular vesicles and the modification of bioscaffold materials. CONCLUSION Dental pulp tissue engineering has had breakthroughs in preclinical and clinical studies in vivo. Overcoming difficulties in pulpal angiogenesis and neurogenesis, and achieving functional pulp regeneration will lead to a significant impact in endodontics.
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Affiliation(s)
- Wanting Su
- School of Stomatology, Jinan University, Guangzhou, China
| | - Chufang Liao
- School of Stomatology, Jinan University, Guangzhou, China
- Clinical Research Platform for Interdiscipline of Stomatology, Jinan University, Guangzhou, China
- Hospital of stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Xiangning Liu
- School of Stomatology, Jinan University, Guangzhou, China
- Clinical Research Platform for Interdiscipline of Stomatology, Jinan University, Guangzhou, China
- Hospital of stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, China
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Chen Y, Guo B, Zhang Y, Bao X, Li D, Lin J. Injectable hypoxia-preconditioned human exfoliated deciduous teeth stem cells encapsulated within GelMA-AMP microspheres for bone regeneration in periodontitis. Colloids Surf B Biointerfaces 2025; 247:114452. [PMID: 39689590 DOI: 10.1016/j.colsurfb.2024.114452] [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: 09/28/2024] [Revised: 11/21/2024] [Accepted: 12/09/2024] [Indexed: 12/19/2024]
Abstract
Periodontitis, an inflammatory and infectious disease resulting from dental plaque, affects tooth-supporting tissues and interconnects with various systemic conditions. Advancing periodontal tissue regeneration stands as pivotal in periodontitis treatment. Presently, odontogenic stem cells garner substantial interest for dental pulp functional tissue regeneration. Essential to stem cell delivery success is the design of suitable drug delivery vehicles. Hence, this research introduces novel injectable antimicrobial peptide-grafted methacryloyl gelatin (GelMA-AMP) microspheres, housing hypoxia-inducible factor (HIF-1α), ensuring sustained release to stimulate osteogenic differentiation of deciduous dental pulp stem cells (SHEDs). Through in vitro co-culturing and preparation of HIF-1α@GelMA-AMP@SHED cell spheres, they were injected and transplanted into periodontal pockets for periodontitis treatment. Results display microsphere sizes averaging 93.92 ± 6.00 μm, akin to human dental pulp, showcasing commendable cytocompatibility and in vitro antibacterial properties. Additionally, GelMA-AMP microspheres carrying HIF-1α enhance cell adhesion, proliferation, and extracellular matrix protein secretion. Notably, HIF-1α@GelMA-AMP@SHED microspheres were effective in reducing periodontal inflammation in vivo and promoting vascularization and tissue regeneration in the periodontal region. Consequently, the application potential of HIF-1α@GelMA-AMP@SHED hydrogel microspheres in periodontitis treatment appears promising.
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Affiliation(s)
- Yu Chen
- Department of Stomatology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Department of Stomatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510000, China
| | - Bing Guo
- Department of Stomatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510000, China
| | - Yanqing Zhang
- Department of Stomatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510000, China
| | - Xinyu Bao
- Department of Stomatology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Dan Li
- Department of Stomatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510000, China
| | - Jun Lin
- Department of Stomatology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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Yuliati Y, Mahdani FY, Margaretha SA, Yastuti WTP, Surboyo MDC, Aljunaid MA, Qaid HR, Ridwan RD, Diyatri I. The EGCG and α-Mangosteen Stimulate SHED-IL10 and SHED-LL37 Metabolite Concentration. Eur J Dent 2024; 18:138-142. [PMID: 37059448 PMCID: PMC10959608 DOI: 10.1055/s-0043-1761460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2023] Open
Abstract
OBJECTIVE Stem cells of human exfoliated deciduous teeth (SHED) metabolites are secreted molecules from SHED, namely cytokines, chemokines, and growth factors. The metabolite can be used in various regenerative therapy based on cell-free immunomodulatory potential effects, like interleukin 10 (IL-10) and LL37. This molecule can stimulate with epigallocatechin gallate (EGCG) and α-mangosteen and has been proven to have anti-inflammatory and antibacterial effects. This study aimed to identify the effect of EGCG and α-mangosteen to SHED metabolite, called SHED-IL10 and SHED-LL37, from six passages to obtain the optimum stimulation and able to use as periodontitis regeneration treatment. MATERIALS AND METHODS The six different passages of SHED were prepared in Dulbecco's modified Eagle medium and added with EGCG 80% (10 μM), EGCG 95% (10 μM), or α-mangosteen (10 μM). After a 24 hours incubation, each passage was measured with the metabolite concentration, SHED-IL10 and SHED-LL37, with human IL-10 and LL37 using enzyme-linked immunosorbent assay. Each different concentration was then analyzed statistically. RESULTS The addition of EGCG 95% is able to stimulate the SHED-IL10 optimum concentration in passage 1 (p < 0.01). But, in the different conditions, the addition of EGCG 80%, EGCG 95%, and α-mangosteen was able to stimulate the SHED-LL37 optimum concentration in passage 2 (p < 0.001). CONCLUSION The addition of EGCG and α-mangosteen can stimulate the SHED-IL10 and SHED-LL37 concentrations. These two metabolites are promising as regenerative therapy through anti-inflammatory and antibacterial properties.
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Affiliation(s)
- Yuliati Yuliati
- Doctoral Program, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
- Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Fatma Yasmin Mahdani
- Oral Medicine Study Program, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
- Department of Oral Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Sellyn Angelina Margaretha
- Bachelor of Dental Science Program. Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | | | | | - Mohammed Ahmed Aljunaid
- Doctoral Program, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
- Department of Oral and Dental Medicine, Faculty of Medicine, Taiz University, Taiz, Yemen
- Faculty of Oral and Dental Medicine, Al-Saeed University, Taiz, Yemen
| | - Huda Rashad Qaid
- Doctoral Program, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
- Faculty of Oral and Dental Medicine, Al-Saeed University, Taiz, Yemen
| | - Rini Devijanti Ridwan
- Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Indeswati Diyatri
- Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
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Santilli F, Fabrizi J, Santacroce C, Caissutti D, Spinello Z, Candelise N, Lancia L, Pulcini F, Delle Monache S, Mattei V. Analogies and Differences Between Dental Stem Cells: Focus on Secretome in Combination with Scaffolds in Neurological Disorders. Stem Cell Rev Rep 2024; 20:159-174. [PMID: 37962698 PMCID: PMC10799818 DOI: 10.1007/s12015-023-10652-9] [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] [Accepted: 11/02/2023] [Indexed: 11/15/2023]
Abstract
Mesenchymal stem cells (MSCs) are well known for their beneficial effects, differentiation capacity and regenerative potential. Dental-derived MSCs (DSCs) are more easily accessible and have a non-invasive isolation method rather than MSCs isolated from other sources (umbilical cord, bone marrow, and adipose tissue). In addition, DSCs appear to have a relevant neuro-regenerative potential due to their neural crest origin. However, it is now known that the beneficial effects of MSCs depend, at least in part, on their secretome, referring to all the bioactive molecules (neurotrophic factors) released in the conditioned medium (CM) or in the extracellular vesicles (EVs) in particular exosomes (Exos). In this review, we described the similarities and differences between various DSCs. Our focus was on the secretome of DSCs and their applications in cell therapy for neurological disorders. For neuro-regenerative purposes, the secretome of different DSCs has been tested. Among these, the secretome of dental pulp stem cells and stem cells from human exfoliated deciduous teeth have been the most widely studied. Both CM and Exos obtained from DSCs have been shown to promote neurite outgrowth and neuroprotective effects as well as their combination with scaffold materials (to improve their functional integration in the tissue). For these reasons, the secretome obtained from DSCs in combination with scaffold materials may represent a promising tissue engineering approach for neuroprotective and neuro-regenerative treatments.
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Affiliation(s)
- Francesca Santilli
- Biomedicine and Advanced Technologies Rieti Center, "Sabina Universitas", Via A.M. Ricci 35/A, 02100, Rieti, Italy
| | - Jessica Fabrizi
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Costantino Santacroce
- Biomedicine and Advanced Technologies Rieti Center, "Sabina Universitas", Via A.M. Ricci 35/A, 02100, Rieti, Italy
| | - Daniela Caissutti
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Zaira Spinello
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Niccolò Candelise
- National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 29900161, Rome, Italy
| | - Loreto Lancia
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy
| | - Fanny Pulcini
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy
| | - Simona Delle Monache
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy.
| | - Vincenzo Mattei
- Dipartimento di Scienze della Vita, della Salute e delle Professioni Sanitarie, Link Campus University, Via del Casale di San Pio V 44, 00165, Rome, Italy.
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Tyagi A, Shetty J, Shetty S, Kumar BM, Shetty AV, Nair MR. Antibacterial and Immunomodulatory Properties of Stem Cells from Human Exfoliated Deciduous Teeth: An In Vitro Study. Int J Clin Pediatr Dent 2023; 16:240-246. [PMID: 38268633 PMCID: PMC10804301 DOI: 10.5005/jp-journals-10005-2683] [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] [Indexed: 01/26/2024] Open
Abstract
Stem cells from human exfoliated deciduous teeth (SHED) provide an important autologous source for stem cell-based regenerative therapies with their easy acquisition and multipotency. However, the understanding of their antibacterial and immunomodulatory properties is limited. This in vitro research aims to determine whether SHED inhibits the growth of Streptococcus mutans (S. mutans) and Enterococcus faecalis (E. faecalis), as well as whether or not it has immunomodulatory effects by measuring interleukins (ILs)-2 and -6 levels. SHEDs were derived from the pulp of deciduous teeth that had undergone up to two-thirds of their roots' resorption. Isolated SHEDs were characterized on their morphological features, viability, assessment of surface markers, and in vitro induction into osteocytes and adipocytes. SHED was tested for its antibacterial efficacy against S. mutans and E. faecalis using a colony-forming units (CFU) assay. Lastly, we checked the cytokine levels by enzyme-linked immune sorbent assay (ELISA) for assessing the immunomodulatory properties of SHED. The results showed that the established SHED had fibroblastic morphology with higher viability. The ability to differentiate into osteocytes and adipocytes, as well as the expression of stem cell-specific markers, demonstrated their potential and flexibility under in vitro settings. SHED demonstrated antibacterial characteristics by significantly (p < 0.05) lowering S. mutans CFU, whereas E. faecalis CFU was either unaffected by or just slightly affected by the cells. SHED also helped keep inflammatory indicators, including IL-2 and IL-6, at stable levels when compared to the control. The results indicate that SHED may aid in preventing or reducing an infection due to its antibacterial activity and may provide immunomodulatory activities by controlling the production of cytokines. How to cite this article Tyagi A, Shetty J, Shetty S, et al. Antibacterial and Immunomodulatory Properties of Stem Cells from Human Exfoliated Deciduous Teeth: An In Vitro Study. Int J Clin Pediatr Dent 2023;16(S-3):S240-S246.
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Affiliation(s)
- Akanksha Tyagi
- Department of Pedodontics and Preventive Dentistry, A B Shetty Memorial Institute of Dental Sciences, NITTE (Deemed to be University), Mangaluru, Karnataka, India
| | - Jayaprakasha Shetty
- Department of Centre for Stem Cell Research and Regenerative Medicine, K S Hegde Medical Academy, NITTE (Deemed to be University), Mangaluru, Karnataka, India
| | - Shriya Shetty
- Department of Microbiology, K S Hegde Medical Academy, NITTE (Deemed to be University), Mangaluru, Karnataka, India
| | - Basavarajappa Mohana Kumar
- Department of Centre for Stem Cell Research and Regenerative Medicine, K S Hegde Medical Academy, NITTE (Deemed to be University), Mangaluru, Karnataka, India
| | - Alandur Veena Shetty
- Department of Microbiology, K S Hegde Medical Academy, NITTE (Deemed to be University), Mangaluru, Karnataka, India
| | - Manju Raman Nair
- Department of Pedodontics and Preventive Dentistry, A B Shetty Memorial Institute of Dental Sciences, NITTE (Deemed to be University), Mangaluru, Karnataka, India
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Fawzy El-Sayed KM, Rudert A, Geiken A, Tölle J, Mekhemar M, Dörfer CE. Toll-like receptor expression profile of stem/progenitor cells from human exfoliated deciduous teeth. Int J Paediatr Dent 2023; 33:607-614. [PMID: 37158295 DOI: 10.1111/ipd.13080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 03/31/2023] [Accepted: 05/05/2023] [Indexed: 05/10/2023]
Abstract
BACKGROUND Stem/progenitor cells from human exfoliated deciduous teeth (SHED) show remarkable pluripotent, regenerative, and immunological capacities. During in vivo regenerative processes, there could be the presence of SHED in the surrounding inflammatory microenvironment, through toll-like receptors (TLRs). AIM The aim of this paper was to present a characteristic TLR expression profile on SHED for the first time. DESIGN Cells were harvested from extracted primary teeth (n = 10), anti-STRO-1 immunomagnetically sorted and cultivated, through colony-forming units (CFUs). SHED were examined for mesenchymal stem/progenitor cell traits, including the expression of clusters of differentiation (CDs) 14, 34, 45, 73, 90, 105, and 146, and their multilineage differentiation aptitude. TLRs 1-10 expression was investigated for SHED in uninflamed and inflamed (25 ng/mL IL-1β, 103 U/mL IFN-γ, 50 ng/mL TNF-α, and 3 × 103 U/mL IFN-α; SHED-i) microenvironmental conditions. RESULTS SHED were negative for CDs 14, 34, and 45, but were positive for CDs 73, 90, 105, and 146, and demonstrated characteristic multilineage differentiation. In an uninflamed microenvironment, SHED expressed TLRs 1, 2, 3, 4, 6, 8, 9, and 10. The inflammatory microenvironment downregulated TLR7 significantly on gene level and upregulated TLR8 on gene and protein levels (p < .05; Wilcoxon signed-rank test). CONCLUSION There appears to be a unique TLR expression profile on SHED, which could modulate their immunological and regenerative abilities in oral tissue engineering approaches.
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Affiliation(s)
- Karim M Fawzy El-Sayed
- Conservative Dentistry and Periodontology Department, Christian Albrechts University, Kiel, Germany
- Oral Medicine and Periodontology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt
- Stem Cells and Tissue Engineering Unit, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Antonia Rudert
- Conservative Dentistry and Periodontology Department, Christian Albrechts University, Kiel, Germany
| | - Antje Geiken
- Conservative Dentistry and Periodontology Department, Christian Albrechts University, Kiel, Germany
| | - Johannes Tölle
- Conservative Dentistry and Periodontology Department, Christian Albrechts University, Kiel, Germany
| | - Mohamed Mekhemar
- Conservative Dentistry and Periodontology Department, Christian Albrechts University, Kiel, Germany
| | - Christof E Dörfer
- Conservative Dentistry and Periodontology Department, Christian Albrechts University, Kiel, Germany
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Ren X, Zhuang H, Zhang Y, Zhou P. Cerium oxide nanoparticles-carrying human umbilical cord mesenchymal stem cells counteract oxidative damage and facilitate tendon regeneration. J Nanobiotechnology 2023; 21:359. [PMID: 37789395 PMCID: PMC10546722 DOI: 10.1186/s12951-023-02125-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 09/21/2023] [Indexed: 10/05/2023] Open
Abstract
BACKGROUND Tendon injuries have a high incidence and limited treatment options. Stem cell transplantation is essential for several medical conditions like tendon injuries. However, high local concentrations of reactive oxygen species (ROS) inhibit the activity of transplanted stem cells and hinder tendon repair. Cerium oxide nanoparticles (CeONPs) have emerged as antioxidant agents with reproducible reducibility. RESULTS In this study, we synthesized polyethylene glycol-packed CeONPs (PEG-CeONPs), which were loaded into the human umbilical cord mesenchymal stem cells (hUCMSCs) to counteract oxidative damage. H2O2 treatment was performed to evaluate the ROS scavenging ability of PEG-CeONPs in hUCMSCs. A rat model of patellar tendon defect was established to assess the effect of PEG-CeONPs-carrying hUCMSCs in vivo. The results showed that PEG-CeONPs exhibited excellent antioxidant activity both inside and outside the hUCMSCs. PEG-CeONPs protect hUCMSCs from senescence and apoptosis under excessive oxidative stress. Transplantation of hUCMSCs loaded with PEG-CeONPs reduced ROS levels in the tendon injury area and facilitated tendon healing. Mechanistically, NFκB activator tumor necrosis factor α and MAPK activator dehydrocrenatine, reversed the therapeutic effect of PEG-CeONPs in hUCMSCs, indicating that PEG-CeONPs act by inhibiting the NFκB and MAPK signaling pathways. CONCLUSIONS The carriage of the metal antioxidant oxidase PEG-CeONPs maintained the ability of hUCMSCs in the injured area, reduced the ROS levels in the microenvironment, and facilitated tendon regeneration. The data presented herein provide a novel therapeutic strategy for tendon healing and new insights into the use of stem cells for disease treatment.
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Affiliation(s)
- Xunshan Ren
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China
| | - Huangming Zhuang
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yuelong Zhang
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China
| | - Panghu Zhou
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China.
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Sugiaman VK, Djuanda R, Pranata N, Naliani S, Demolsky WL. Tissue Engineering with Stem Cell from Human Exfoliated Deciduous Teeth (SHED) and Collagen Matrix, Regulated by Growth Factor in Regenerating the Dental Pulp. Polymers (Basel) 2022; 14:polym14183712. [PMID: 36145860 PMCID: PMC9503223 DOI: 10.3390/polym14183712] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 08/25/2022] [Accepted: 09/02/2022] [Indexed: 11/16/2022] Open
Abstract
Maintaining dental pulp vitality and preventing tooth loss are two challenges in endodontic treatment. A tooth lacking a viable pulp loses its defense mechanism and regenerative ability, making it more vulnerable to severe damage and eventually necessitating extraction. The tissue engineering approach has drawn attention as an alternative therapy as it can regenerate dentin-pulp complex structures and functions. Stem cells or progenitor cells, extracellular matrix, and signaling molecules are triad components of this approach. Stem cells from human exfoliated deciduous teeth (SHED) are a promising, noninvasive source of stem cells for tissue regeneration. Not only can SHEDs regenerate dentin-pulp tissues (comprised of fibroblasts, odontoblasts, endothelial cells, and nerve cells), but SHEDs also possess immunomodulatory and immunosuppressive properties. The collagen matrix is a material of choice to provide structural and microenvironmental support for SHED-to-dentin pulp tissue differentiation. Growth factors regulate cell proliferation, migration, and differentiation into specific phenotypes via signal-transduction pathways. This review provides current concepts and applications of the tissue engineering approach, especially SHEDs, in endodontic treatment.
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Affiliation(s)
- Vinna K Sugiaman
- Department of Oral Biology, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Rudy Djuanda
- Department of Conservative Dentistry and Endodontic, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Natallia Pranata
- Department of Oral Biology, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Silvia Naliani
- Department of Prosthodontics, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
| | - Wayan L Demolsky
- Department of Oral Biology, Faculty of Dentistry, Maranatha Christian University, Bandung 40164, Indonesia
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Bar JK, Lis-Nawara A, Grelewski PG. Dental Pulp Stem Cell-Derived Secretome and Its Regenerative Potential. Int J Mol Sci 2021; 22:ijms222112018. [PMID: 34769446 PMCID: PMC8584775 DOI: 10.3390/ijms222112018] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 11/02/2021] [Accepted: 11/04/2021] [Indexed: 12/11/2022] Open
Abstract
The therapeutic potential of the dental pulp stem (DSC) cell-derived secretome, consisting of various biomolecules, is undergoing intense research. Despite promising in vitro and in vivo studies, most DSC secretome-based therapies have not been implemented in human medicine because the paracrine effect of the bioactive factors secreted by human dental pulp stem cells (hDPSCs) and human exfoliated deciduous teeth (SHEDs) is not completely understood. In this review, we outline the current data on the hDPSC- and SHED-derived secretome as a potential candidate in the regeneration of bone, cartilage, and nerve tissue. Published reports demonstrate that the dental MSC-derived secretome/conditional medium may be effective in treating neurodegenerative diseases, neural injuries, cartilage defects, and repairing bone by regulating neuroprotective, anti-inflammatory, antiapoptotic, and angiogenic processes through secretome paracrine mechanisms. Dental MSC-secretomes, similarly to the bone marrow MSC-secretome activate molecular and cellular mechanisms, which determine the effectiveness of cell-free therapy. Many reports emphasize that dental MSC-derived secretomes have potential application in tissue-regenerating therapy due to their multidirectional paracrine effect observed in the therapy of many different injured tissues.
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10
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Bhandary M, Rao S, Shetty AV, Kumar BM, Hegde AM, Chhabra R. Comparison of stem cells from human exfoliated deciduous posterior teeth with varying levels of root resorption. Stem Cell Investig 2021; 8:15. [PMID: 34527730 DOI: 10.21037/sci-2020-039] [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: 08/26/2020] [Accepted: 05/17/2021] [Indexed: 12/21/2022]
Abstract
Background Stem cells from human exfoliated deciduous teeth (SHED) are regarded as an attractive cell source for tissue regeneration. However, the effect of different levels of root resorption on the characteristics of SHED remains less understood. Thus, the tooth source that is most suitable for the isolation of SHEDs needs to be determined. To compare cellular and biological characteristics of stem cells from human exfoliated deciduous posterior teeth with varying levels of root resorption. Methods The pulp was obtained from the deciduous posterior teeth depending on the level of root resorption, and isolated SHEDs were grouped as follows: Teeth with 0 to 1/3rd root resorption as SHEDs (G1) and 1/3rd to 2/3rd root resorption as SHEDs (G2). Teeth were also collected from >2/3rd root resorption status, but failed to establish primary culture of SHED as the availability of pulp tissue was too less. Later, isolated SHEDs were compared on their morphology, viability, growth kinetics, colony-forming ability, expression of cell surface markers and in vitro differentiation into osteocytes and adipocytes. Results No major differences were observed in terms of cellular morphology, viability, proliferation rate, colony-forming ability, cell surface markers expression, and mesenchymal lineage differentiation of SHEDs isolated from posterior teeth with 0 to 1/3rd and 1/3rd to 2/3rd root resorption. However, SHED from teeth with 0 to 1/3rd root resorption (G1) displayed relatively higher proliferation capacity and expression of selected markers. Conclusions Collectively, SHEDs (G1) and SHEDs (G2) showed comparable cellular and biological characteristics that enable their possible applications in regenerative therapies.
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Affiliation(s)
- Meghna Bhandary
- Department of Pediatric and Preventive Dentistry, A. B. Shetty Memorial Institute of Dental Sciences, Nitte University (Deemed to be University), Mangaluru, India
| | - Shama Rao
- Nitte University Centre for Stem Cell Research and Regenerative Medicine, K. S. Hegde Medical Academy, Nitte University (Deemed to be University), Mangaluru, India
| | - Alandur Veena Shetty
- Nitte University Centre for Stem Cell Research and Regenerative Medicine, K. S. Hegde Medical Academy, Nitte University (Deemed to be University), Mangaluru, India
| | - Basavarajappa Mohana Kumar
- Nitte University Centre for Stem Cell Research and Regenerative Medicine, K. S. Hegde Medical Academy, Nitte University (Deemed to be University), Mangaluru, India
| | - Amitha Mahesh Hegde
- Department of Pediatric and Preventive Dentistry, A. B. Shetty Memorial Institute of Dental Sciences, Nitte University (Deemed to be University), Mangaluru, India
| | - Rachaita Chhabra
- Department of Pediatric and Preventive Dentistry, A. B. Shetty Memorial Institute of Dental Sciences, Nitte University (Deemed to be University), Mangaluru, India
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Bhandi S, Alkahtani A, Mashyakhy M, Abumelha AS, Albar NHM, Renugalakshmi A, Alkahtany MF, Robaian A, Almeslet AS, Patil VR, Varadarajan S, Balaji TM, Reda R, Testarelli L, Patil S. Effect of Ascorbic Acid on Differentiation, Secretome and Stemness of Stem Cells from Human Exfoliated Deciduous Tooth (SHEDs). J Pers Med 2021; 11:jpm11070589. [PMID: 34206203 PMCID: PMC8304986 DOI: 10.3390/jpm11070589] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 06/16/2021] [Accepted: 06/20/2021] [Indexed: 12/23/2022] Open
Abstract
Stem cells from human exfoliated deciduous teeth (SHEDs) are considered a type of mesenchymal stem cells (MSCs) because of their unique origin from the neural crest. SHEDs can self-renewal and multi-lineage differentiation with the ability to differentiate into odontoblasts, osteoblast, chondrocytes, neuronal cells, hepatocytes, adipocytes, etc. They are emerging as an ideal source of MSCs because of their easy availability and extraordinary cell number. Ascorbic acid, or vitamin C, has many cell-based applications, such as bone regeneration, osteoblastic differentiation, or extracellular matrix production. It also impacts stem cell plasticity and the ability to sustain pluripotent activity. In this study, we evaluate the effects of ascorbic acid on stemness, paracrine secretion, and differentiation into osteoblast, chondrocytes, and adipocytes. SHEDs displayed enhanced multifaceted activity, which may have applications in regenerative therapy.
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Affiliation(s)
- Shilpa Bhandi
- Department of Restorative Dental Sciences, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia; (S.B.); (M.M.); (N.H.M.A.)
| | - Ahmed Alkahtani
- Department of Restorative Dental Sciences, Division of Endodontics, College of Dentistry, King Saud University, Riyadh 11451, Saudi Arabia; (A.A.); (M.F.A.)
| | - Mohammed Mashyakhy
- Department of Restorative Dental Sciences, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia; (S.B.); (M.M.); (N.H.M.A.)
| | - Abdulaziz S. Abumelha
- Department of Restorative Dental Sciences, College of Dentistry, King Khalid University, Abha 61421, Saudi Arabia;
| | - Nassreen Hassan Mohammad Albar
- Department of Restorative Dental Sciences, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia; (S.B.); (M.M.); (N.H.M.A.)
| | - Apathsakayan Renugalakshmi
- Department of Preventive Dental Sciences, Pedodontics Division, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia;
| | - Mazen F. Alkahtany
- Department of Restorative Dental Sciences, Division of Endodontics, College of Dentistry, King Saud University, Riyadh 11451, Saudi Arabia; (A.A.); (M.F.A.)
| | - Ali Robaian
- Department of Conservative Dental Sciences, College of Dentistry, Prince Sattam bin Abdulaziz University, Alkharj 11942, Saudi Arabia;
| | - Asma Saleh Almeslet
- Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, Riyadh Elm University, Riyadh 12611, Saudi Arabia;
| | | | - Saranya Varadarajan
- Department of Oral Pathology and Microbiology, Sri Venkateswara Dental College and Hospital, Chennai 600130, India;
| | - Thodur Madapusi Balaji
- Department of Periodontology, Tagore Dental College and Hospital, Chennai 600127, India;
| | - Rodolfo Reda
- Department of Oral and Maxillofacial Sciences, Sapienza University of Rome, 00161 Rome, Italy; (R.R.); (L.T.)
| | - Luca Testarelli
- Department of Oral and Maxillofacial Sciences, Sapienza University of Rome, 00161 Rome, Italy; (R.R.); (L.T.)
| | - Shankargouda Patil
- Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia
- Correspondence:
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12
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Inada E, Saitoh I, Kubota N, Iwase Y, Kiyokawa Y, Noguchi H, Yamasaki Y, Sato M. RNA analysis based on a small number of manually isolated fixed cells (RNA-snMIFxC) to profile stem cells from human deciduous tooth-derived dental pulp cells. Biol Proced Online 2021; 23:12. [PMID: 34116635 PMCID: PMC8194139 DOI: 10.1186/s12575-021-00149-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Accepted: 05/17/2021] [Indexed: 01/09/2023] Open
Abstract
Background Expression of stemness factors, such as octamer-binding transcription factor 3/4 (OCT3/4), sex determining region Y-box 2 (SOX2), and alkaline phosphatase (ALP) in human deciduous tooth-derived dental pulp cells (HDDPCs) can be assessed through fixation and subsequent immuno- or cytochemical staining. Fluorescence-activated cell sorting (FACS), a powerful system to collect cells of interest, is limited by the instrument cost and difficulty in handling. Magnetic-activated cell sorting is inexpensive compared to FACS, but is confined to cells with surface expression of the target molecule. In this study, a simple and inexpensive method was developed for the molecular analysis of immuno- or cytochemically stained cells with intracellular expression of a target molecule, through isolation of a few cells under a dissecting microscope using a mouthpiece-controlled micropipette. Results Two or more colored cells (~ 10), after staining with a chromogen such a 3,3′-diaminobenzidine, were successfully segregated from unstained cells. Expression of glyceraldehyde 3-phosphate dehydrogenase, a housekeeping gene, was discernible in all samples, while the expression of stemness genes (such as OCT3/4, SOX2, and ALP) was confined to positively stained cells. Conclusion These findings indicate the fidelity of these approaches in profiling cells exhibiting cytoplasmic or nuclear localization of stemness-specific gene products at a small-scale.
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Affiliation(s)
- Emi Inada
- Department of Pediatric Dentistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 890-8544, Japan
| | - Issei Saitoh
- Department of Pediatric Dentistry, Asahi University School of Dentistry, Gifu, 501-0296, Japan.,Division of Pediatric Dentistry, Graduate School of Medical and Dental Science, Niigata University, Niigata, 951-8514, Japan
| | - Naoko Kubota
- Department of Pediatric Dentistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 890-8544, Japan
| | - Yoko Iwase
- Division of Pediatric Dentistry, Graduate School of Medical and Dental Science, Niigata University, Niigata, 951-8514, Japan.,Department of Dentistry for the Disabled, Asahi University School of Dentistry, Gifu, 501-0296, Japan
| | - Yuki Kiyokawa
- Division of Pediatric Dentistry, Graduate School of Medical and Dental Science, Niigata University, Niigata, 951-8514, Japan
| | - Hirofumi Noguchi
- Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, 903-0215, Japan
| | - Youichi Yamasaki
- Department of Pediatric Dentistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 890-8544, Japan
| | - Masahiro Sato
- Department of Genome Medicine, National Center for Child Health and Development, 2-10-1, Tokyo, 157-8535, Japan. .,Section of Gene Expression Regulation, Frontier Science Research Center, Kagoshima University, Kagoshima, 890-8544, Japan.
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13
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Kornsuthisopon C, Manokawinchoke J, Sonpoung O, Osathanon T, Damrongsri D. Interleukin 15 participates in Jagged1-induced mineralization in human dental pulp cells. Arch Oral Biol 2021; 128:105163. [PMID: 34058721 DOI: 10.1016/j.archoralbio.2021.105163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 04/25/2021] [Accepted: 05/19/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVES Crosstalk between Notch and other cell signaling molecules has been implicated to regulate the osteogenic differentiation. Understanding the interaction between Notch and IL15 is essential to reveal molecular mechanism. Thus, the objective of the present study was to investigate whether IL15 participates in the Notch signaling-induced mineral deposition in human dental pulp cells (hDPs). METHODS hDPs were explanted from dental pulp tissues. To activate Notch signaling, the cells were seeded on Jagged1-immobilized surfaces. The mRNA expression was evaluated using real-time polymerase chain reaction. hDPs were treated with 5-50 ng/mL IL15. Cell viability and proliferation were determined using an MTT assay. Mineral deposition was examined using alizarin red s and Von Kossa staining. In some experiments, the cells were pretreated with a JAK inhibitor prior to stimulation. RESULTS Jagged1 induced IL15 and IL15RA expression in hDPs. IL15 treatment significantly increased mineral deposition at 14 d and upregulated ALP, OCN, OSX, ANKH, and ENPP1 mRNA expression. IL15-induced mineralization was attenuated by JAK inhibitor pretreatment. Further, JAK inhibitor pretreatment inhibited the effect of Jagged1 on hDP mineral deposition. CONCLUSION IL15 promoted the osteogenic differentiation in hDPs. Moreover, IL15 participated in the Jagged1-induced mineralization in hDPs.
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Affiliation(s)
- Chatvadee Kornsuthisopon
- Dental Stem Cell Biology Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Jeeranan Manokawinchoke
- Dental Stem Cell Biology Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Opor Sonpoung
- Oral Biology Research Center, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Thanaphum Osathanon
- Dental Stem Cell Biology Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand; Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Damrong Damrongsri
- Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand.
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Zhou YK, Zhu LS, Huang HM, Cui SJ, Zhang T, Zhou YH, Yang RL. Stem cells from human exfoliated deciduous teeth ameliorate concanavalin A-induced autoimmune hepatitis by protecting hepatocytes from apoptosis. World J Stem Cells 2020; 12:1623-1639. [PMID: 33505604 PMCID: PMC7789126 DOI: 10.4252/wjsc.v12.i12.1623] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 09/20/2020] [Accepted: 10/12/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide, which emphasizes the urgent need to identify novel treatments. Stem cells from human exfoliated deciduous teeth (SHED), which are easy to obtain in a non-invasive manner, show pronounced proliferative and immunomodulatory capacities. AIM To investigate the protective effects of SHED on concanavalin A (ConA)-induced hepatitis in mice, and to elucidate the associated regulatory mechanisms. METHODS We used a ConA-induced acute hepatitis mouse model and an in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis, as well as the associated underlying mechanisms. RESULTS SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3+, CD4+, tumor necrosis-alpha+, and interferon-gamma+ inflammatory cells. Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice. SHED infusion could therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations. Mechanistically, ConA upregulated tumor necrosis-alpha and interferon-gamma expression, which was activated by the nuclear factor-kappa B pathway to induce hepatocyte apoptosis, resulting in acute liver injury. SHED administration protected hepatocytes from ConA-induced apoptosis. CONCLUSION SHED alleviates ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway. Our findings could provide a potential treatment strategy for hepatitis.
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Affiliation(s)
- Yi-Kun Zhou
- Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | - Ling-Su Zhu
- Department of Orthodontics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Hua-Ming Huang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | - Sheng-Jie Cui
- Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | - Ting Zhang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | - Yan-Heng Zhou
- Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
| | - Rui-Li Yang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China.
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