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International Journal of Molecular... Jun 2023Teeth include mesenchymal stem cells (MSCs), which are multipotent cells that promote tooth growth and repair. Dental tissues, specifically the dental pulp and the... (Review)
Review
Teeth include mesenchymal stem cells (MSCs), which are multipotent cells that promote tooth growth and repair. Dental tissues, specifically the dental pulp and the dental bud, constitute a relevant source of multipotent stem cells, known as dental-derived stem cells (d-DSCs): dental pulp stem cells (DPSCs) and dental bud stem cells (DBSCs). Cell treatment with bone-associated factors and stimulation with small molecule compounds are, among the available methods, the ones who show excellent advantages promoting stem cell differentiation and osteogenesis. Recently, attention has been paid to studies on natural and non-natural compounds. Many fruits, vegetables, and some drugs contain molecules that can enhance MSC osteogenic differentiation and therefore bone formation. The purpose of this review is to examine research work over the past 10 years that has investigated two different types of MSCs from dental tissues that are attractive targets for bone tissue engineering: DPSCs and DBSCs. The reconstruction of bone defects, in fact, is still a challenge and therefore more research is needed; the articles reviewed are meant to identify compounds useful to stimulate d-DSC proliferation and osteogenic differentiation. We only consider the results of the research which is encouraging, assuming that the mentioned compounds are of some importance for bone regeneration.
Topics: Osteogenesis; Bone Regeneration; Cell Differentiation; Mesenchymal Stem Cells; Stem Cells; Dental Pulp; Cells, Cultured; Cell Proliferation
PubMed: 37373044
DOI: 10.3390/ijms24129897 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Jun 2022Regenerative endodontic therapy (RET) utilizing tissue engineering approach can promote the regeneration of pulp-dentin complex to restore pulp vascularization,... (Review)
Review
Regenerative endodontic therapy (RET) utilizing tissue engineering approach can promote the regeneration of pulp-dentin complex to restore pulp vascularization, neuralization, immune function and tubular dentin, therefore the regenerated pulp-dentin complex will have normal function. Multiple factors may significantly affect the efficacy of RET, including stem cells, biosignaling molecules and biomaterial scaffolds. Stem cells derived from dental tissues (such as dental pulp stem cells) exhibit certain advantages in RET. Combined application of multiple signaling molecules and activation of signal transduction pathways such as Wnt/β-catenin and BMP/Smad play pivotal roles in enhancing the potential of stem cell migration, proliferation, odontoblastic differentiation, and nerve and blood vessel regeneration. Biomaterials suitable for RET include naturally-derived materials and artificially synthetic materials. Artificially synthetic materials should imitate natural tissues for biomimetic modification in order to realize the temporal and spatial regulation of pulp-dentin complex regeneration. The realization of pulp-dentin complex regeneration depends on two strategies: stem cell transplantation and stem cell homing. Stem cell homing strategy does not require the isolation and culture of stem cells , so is better for clinical application. However, in order to achieve the true regeneration of pulp-dentin complex, problems related to improving the success rate of stem cell homing and promoting their proliferation and differentiation need to be solved. This article reviews the influencing factors of pulp-dentin complex regeneration and related biological strategies, and discusses the future research direction of RET, to provide reference for clinical translation and application of RET.
Topics: Biocompatible Materials; Cell Differentiation; Dental Pulp; Dentin; Stem Cells; Tissue Engineering; beta Catenin
PubMed: 36207838
DOI: 10.3724/zdxbyxb-2022-0046 -
Biomolecules Mar 2024Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not... (Review)
Review
Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not allow for genuine structural regeneration and functional reconstruction of the pulp-dentin complex. In recent years, with the development of tissue engineering and regenerative medicine, research on stem cell-based regenerative endodontic therapy (RET) has achieved satisfactory preliminary results, significantly enhancing its clinical translational prospects. As one of the crucial paracrine effectors, the roles and functions of exosomes in pulp-dentin complex regeneration have gained considerable attention. Due to their advantages of cost-effectiveness, extensive sources, favorable biocompatibility, and high safety, exosomes are considered promising therapeutic tools to promote dental pulp regeneration. Accordingly, in this article, we first focus on the biological properties of exosomes, including their biogenesis, uptake, isolation, and characterization. Then, from the perspectives of cell proliferation, migration, odontogenesis, angiogenesis, and neurogenesis, we aim to reveal the roles and mechanisms of exosomes involved in regenerative endodontics. Lastly, immense efforts are made to illustrate the clinical strategies and influencing factors of exosomes applied in dental pulp regeneration, such as types of parental cells, culture conditions of parent cells, exosome concentrations, and scaffold materials, in an attempt to lay a solid foundation for exploring and facilitating the therapeutic strategy of exosome-based regenerative endodontic procedures.
Topics: Regenerative Endodontics; Exosomes; Dental Pulp; Regeneration; Regenerative Medicine
PubMed: 38540750
DOI: 10.3390/biom14030330 -
Cells Mar 2020We developed a novel dentin-pulp-like organoid. It has both stem-cell and odontoblast characteristics using a mesenchymal cell lineage of human dental-pulp stem cells...
We developed a novel dentin-pulp-like organoid. It has both stem-cell and odontoblast characteristics using a mesenchymal cell lineage of human dental-pulp stem cells (hDPSCs). The mixture of hDPSCs and Matrigel was transferred into the maintenance medium (MM) and divided into four different groups according to how long they were maintained in the odontogenic differentiation medium (ODM). All organoids were harvested at 21 days and analyzed to find the optimal differentiation condition. To assess the re-fabrication of dentin-pulp-like organoid, after dissociation of the organoids, it was successfully regenerated. Additionally, its biological activity was confirmed by analyzing changes of relevant gene expression and performing a histology analysis after adding Biodentine into the ODM. The organoid was cultured for 11 days in the ODM (ODM 11) had the most features of both stem cells and differentiated cells (odontoblasts) as confirmed by relevant gene expression and histology analyses. Micro-computed tomography and an electron microscope also showed mineralization and odontoblastic differentiation. Finally, ODM 11 demonstrated a biologically active response to Biodentine treatment. In conclusion, for the first time, we report the fabrication of a dentin-pulp-like organoid using mesenchymal stem cells. This organoid has potential as a future therapeutic strategy for tooth regeneration.
Topics: Cell Differentiation; Dental Pulp; Humans; Mesenchymal Stem Cells; Organoids; Stem Cells
PubMed: 32155898
DOI: 10.3390/cells9030642 -
Current Issues in Molecular Biology May 2021The role of inflammatory mediators in dental pulp is unique. The local environment of pulp responds to any changes in the physiology that are highly fundamental, like... (Review)
Review
The role of inflammatory mediators in dental pulp is unique. The local environment of pulp responds to any changes in the physiology that are highly fundamental, like odontoblast cell differentiation and other secretory activity. The aim of this review is to assess the role of cathelicidins based on their capacity to heal wounds, their immunomodulatory potential, and their ability to stimulate cytokine production and stimulate immune-inflammatory response in pulp and periapex. Accessible electronic databases were searched to find studies reporting the role of cathelicidins in pulpal inflammation and regeneration published between September 2010 and September 2020. The search was performed using the following databases: Medline, Scopus, Web of Science, SciELO and PubMed. The electronic search was performed using the combination of keywords "cathelicidins" and "dental pulp inflammation". On the basis of previous studies, it can be inferred that LL-37 plays an important role in odontoblastic cell differentiation and stimulation of antimicrobial peptides. Furthermore, based on these outcomes, it can be concluded that LL-37 plays an important role in reparative dentin formation and provides signaling for defense by activating the innate immune system.
Topics: Cathelicidins; Cell Differentiation; Dental Pulp; Humans; Immunomodulation; Inflammation; Odontoblasts; Wound Healing
PubMed: 34068275
DOI: 10.3390/cimb43010010 -
Biomedical Journal Jun 2021Neurotrophic factors play important roles in neuron survival, growth and differentiation. In the present research, the expression of multiple neurotrophins and their...
Neurotrophic factors play important roles in neuron survival, growth and differentiation. In the present research, the expression of multiple neurotrophins and their effects on cell migration were studied in the dental pulp stem cells (DPSCs). Human DPSCs from five patients were cultured. Expression of neurotrophins and their receptors were evaluated by PCR, immunofluorescent staining and ELISA. Scratch assay was performed in the presence or absence of neurotrophic factors. Level of phosphorylated-ERK was evaluated with Western blotting. Neurotrophins were expressed at various levels in the DPSCs. Treatment of 100 ng/ml BDNF or NT4/5 accelerated wound healing in scratch assay and elevated the expression of phosphorylated-ERK. The work indicated that neurotrophins promoted human DPSCs migration in vitro.
Topics: Brain-Derived Neurotrophic Factor; Cell Differentiation; Cell Movement; Cell Survival; Cells, Cultured; Dental Pulp; Humans
PubMed: 32330678
DOI: 10.1016/j.bj.2020.03.010 -
Aging Cell Mar 2024Once tooth development is complete, odontoblasts and their progenitor cells in the dental pulp play a major role in protecting tooth vitality from external stresses....
Once tooth development is complete, odontoblasts and their progenitor cells in the dental pulp play a major role in protecting tooth vitality from external stresses. Hence, understanding the homeostasis of the mature pulp populations is just as crucial as understanding that of the young, developing ones for managing age-related dentinal damage. Here, it is shown that loss of Cpne7 accelerates cellular senescence in odontoblasts due to oxidative stress and DNA damage accumulation. Thus, in Cpne7-null dental pulp, odontoblast survival is impaired, and aberrant dentin is extensively formed. Intraperitoneal or topical application of CPNE7-derived functional peptide, however, alleviates the DNA damage accumulation and rescues the pathologic dentin phenotype. Notably, a healthy dentin-pulp complex lined with metabolically active odontoblasts is observed in 23-month-old Cpne7-overexpressing transgenic mice. Furthermore, physiologic dentin was regenerated in artificial dentinal defects of Cpne7-overexpressing transgenic mice. Taken together, Cpne7 is indispensable for the maintenance and homeostasis of odontoblasts, while promoting odontoblastic differentiation of the progenitor cells. This research thereby introduces its potential in oral disease-targeted applications, especially age-related dental diseases involving dentinal loss.
Topics: Mice; Animals; Aging, Premature; Dental Pulp; Cellular Senescence; Odontoblasts; Cell Differentiation; Mice, Transgenic
PubMed: 38105557
DOI: 10.1111/acel.14061 -
European Journal of Paediatric Dentistry Dec 2020Dental pulp regeneration: An overview of the current approaches. Regenerative Endodontic Procedures (REPs) are biologically based procedures aimed at restoring the... (Review)
Review
Dental pulp regeneration: An overview of the current approaches. Regenerative Endodontic Procedures (REPs) are biologically based procedures aimed at restoring the damaged structures and physiological functions of the pulp-dentine complex. Clinically, two strategies have been proposed so far to induce REP: cell transplantation and cell homing. REPs success relies primarily on the clinical and biological conditions of the tooth; therefore, cell homing strategies will not be consistently successful in every condition. Root canal treatment remains the standard of care for mature teeth with necrotic pulps and closed apex.
Topics: Child; Dental Pulp; Dental Pulp Necrosis; Endodontics; Humans; Regeneration; Root Canal Therapy
PubMed: 33337912
DOI: 10.23804/ejpd.2020.21.04.14 -
The Chinese Journal of Dental Research 2020To investigate the role of microbiota in dentine formation and the characteristics of dental pulp stem cells (DPSCs) in mouse incisors.
OBJECTIVE
To investigate the role of microbiota in dentine formation and the characteristics of dental pulp stem cells (DPSCs) in mouse incisors.
METHODS
The influence of microbiota on dentine was detected via microcomputed tomography (microCT), microhardness testing and haematoxylin-eosin (HE) staining in incisors from germ-free (GF), specific pathogen-free (SPF) and conventionalised (ConvD) mice. Cell Counting Kit-8 (CCK-8) assay, alizarin red staining and expression of dentine sialophosphoprotein (DSPP), alkaline phosphatase (ALP) and bone sialoprotein (BSP) via real-time polymerase chain reaction (PCR) were used to evaluate the biological characteristics of DPSCs derived from mice of different microbiota status.
RESULTS
MicroCT showed that the incisors in the GF and ConvD groups had comparable dentine thickness to those in the SPF group. Microhardness testing showed a lower dentine hardness value in GF incisors compared to SPF, while HE staining showed that GF incisors exhibited thicker predentine than SPF incisors. There was no difference between the ConvD and SPF groups. DPSCs from GF mice showed no significant difference in proliferation rate to SPF and ConvD DPSCs. DPSCs from GF mice formed less mineral deposition and expressed lower levels of osteo-/odontogenic differentiation-related genes including ALP, BSP and DSPP than SPF and ConvD DPSCs. The absence of microbiota in GF mice resulted in a lower dentine hardness value, thicker predentine and impaired osteo-/odontogenic differentiation capacity.
CONCLUSION
The absence of microbiota impaired the dentine mineralisation and osteo-/odontogenic differentiation abilities of DPSCs.
Topics: Animals; Cell Differentiation; Cell Proliferation; Cells, Cultured; Dental Pulp; Dentin; Mice; Microbiota; Stem Cells; X-Ray Microtomography
PubMed: 32974617
DOI: 10.3290/j.cjdr.a45221 -
International Endodontic Journal Jun 2022The aim of this study was to investigate the effect of type 2 diabetes (T2D) on clinically normal dental pulp tissue by using special stains and immunohistochemistry...
AIM
The aim of this study was to investigate the effect of type 2 diabetes (T2D) on clinically normal dental pulp tissue by using special stains and immunohistochemistry (IHC) to determine the morphology of the coronal pulp and distribution of immune markers in non-T2D and T2D groups.
METHODOLOGY
Ethics approval for this in vitro pilot study was obtained from the University of Otago Human Ethics Committee (16/069). Twenty extracted permanent molar teeth diagnosed as having clinically normal pulp status were collected. Ten teeth were from participants with well-controlled T2D and ten from participants without diabetes (non-T2D). Each tooth was sectioned transversely at the cemento-enamel junction before the crowns were decalcified and embedded in paraffin. Sections were stained with haematoxylin and eosin, Massons trichrome, and van Gieson stains for histological and morphological evaluation. IHC using anti-CD4, anti-CD68 and anti-CD83 and anti-IL1β, anti-IL6, anti-IL17, anti-TNF-α, anti-TLR2, anti-TLR4 and anti-FOXP3 identified proteins of interest. Qualitative and semi-quantitative analyses evaluated the morphology of the dental pulp and protein expression. Data analyses were performed with GraphPad Prism, using Student's t-test and multiple regression using SPSS at p < .05.
RESULTS
Special stains demonstrated morphological differences in the T2D dental pulp compared with non-T2D. Qualitative analysis indicated that the pulp in the T2D samples was consistently less cellular, less vascular, showed evidence of thickened blood vessel walls, increased pulp calcification and collagen deposition. Semi-quantitative analysis of IHC samples showed the T2D pulp had significantly increased expression of macrophage and dendritic cell markers CD68 (p < .001) and CD83 (p = .04), and there was significantly greater expression of inflammatory cytokines IL1β (p = .01), IL6 (p < .0001), IL17 (p < .0001) and TNF-α (p = .01). T2D samples showed a significant increase in markers of innate inflammation, TLR2 (p < .001) and TLR4 (p < .001) and decreased expression of regulatory T-cell marker, FOXP3 (p = .01). Multiple regression showed that age-corrected differences were statistically significant.
CONCLUSION
Preliminary findings suggest that T2D may exert a similar response in the pulp to complications in other body sites. Hyperglycaemia is associated with changes in the morphology of the clinically normal dental pulp with altered immune cell and cytokine expression.
Topics: Biomarkers; Dental Pulp; Diabetes Mellitus, Type 2; Humans; Pilot Projects; Tooth; Tumor Necrosis Factor Inhibitors
PubMed: 35322881
DOI: 10.1111/iej.13732