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Tissue Engineering. Part B, Reviews Apr 2019Animal models are essential for tissue regeneration studies. This review summarizes and discusses the small and large animal models, including mouse, ferret, dog, and... (Review)
Review
Animal models are essential for tissue regeneration studies. This review summarizes and discusses the small and large animal models, including mouse, ferret, dog, and miniswine that have been utilized to experiment and to demonstrate stem cell-mediated dental pulp tissue regeneration. We describe the models based on the location where the tissue regeneration is tested-either ectopic, semiorthotopic, or orthotopic. Developing and utilizing optimal animal models for both mechanistic and translational studies of pulp regeneration are of critical importance to advance this field.
Topics: Animals; Dental Pulp; Humans; Regeneration; Stem Cell Transplantation; Stem Cells; Tissue Engineering
PubMed: 30284967
DOI: 10.1089/ten.TEB.2018.0194 -
BioMed Research International 2020Dental pulp stem cells (DPSCs) are increasingly being advocated for regenerative medicine-based therapies. However, significant heterogeneity in the genotypic/phenotypic...
Dental pulp stem cells (DPSCs) are increasingly being advocated for regenerative medicine-based therapies. However, significant heterogeneity in the genotypic/phenotypic properties of DPSC subpopulations exist, influencing their therapeutic potentials. As most studies have established DPSC heterogeneity using 2D culture approaches, we investigated whether heterogeneous DPSC proliferative and contraction/remodelling capabilities were further evident within 3D type I collagen gels . DPSC subpopulations were isolated from human third molars and identified as high/low proliferative and multipotent/unipotent, following culture expansion and population doubling (PD) analysis. High proliferative/multipotent DPSCs, such as A3 (30 PDs and 80 PDs), and low proliferative/unipotent DPSCs, such as A1 (17 PDs), were cultured in collagen gels for 12 days, either attached or detached from the surrounding culture plastic. Collagen architecture and high proliferative/multipotent DPSC morphologies were visualised by Scanning Electron Microscopy and FITC-phalloidin/Fluorescence Microscopy. DPSC proliferation (cell counts), contraction (% diameter reductions), and remodelling (MMP-2/MMP-9 gelatin zymography) of collagen gels were also evaluated. Unexpectedly, no proliferation differences existed between DPSCs, A3 (30 PDs) and A1 (17 PDs), although A3 (80 PDs) responses were significantly reduced. Despite rapid detached collagen gel contraction with A3 (30 PDs), similar contraction rates were determined with A1 (17 PDs), although A3 (80 PDs) contraction was significantly impaired. Gel contraction correlated to distinct gelatinase profiles. A3 (30 PDs) possessed superior MMP-9 and comparable MMP-2 activities to A1 (17 PDs), whereas A3 (80 PDs) had significantly reduced MMP-2/MMP-9. High proliferative/multipotent DPSCs, A3 (30 PDs), further exhibited fibroblast-like morphologies becoming polygonal within attached gels, whilst losing cytoskeletal organization and fibroblastic morphologies in detached gels. This study demonstrates that heterogeneity exists in the gel contraction and MMP expression/activity capabilities of DPSCs, potentially reflecting differences in their abilities to degrade biomaterial scaffolds and regulate cellular functions in 3D environments and their regenerative properties overall. Thus, such findings enhance our understanding of the molecular and phenotypic characteristics associated with high proliferative/multipotent DPSCs.
Topics: Biocompatible Materials; Cell Proliferation; Cells, Cultured; Collagen Type I; Dental Pulp; Fibroblasts; Gels; Humans; Matrix Metalloproteinases; Stem Cells
PubMed: 32964026
DOI: 10.1155/2020/3034727 -
Advances in Dental Research Jul 2011For tissue engineering strategies, the choice of an appropriate scaffold is the first and certainly a crucial step. A vast variety of biomaterials is available: natural... (Review)
Review
For tissue engineering strategies, the choice of an appropriate scaffold is the first and certainly a crucial step. A vast variety of biomaterials is available: natural or synthetic polymers, extracellular matrix, self-assembling systems, hydrogels, or bioceramics. Each material offers a unique chemistry, composition and structure, degradation profile, and possibility for modification. The role of the scaffold has changed from passive carrier toward a bioactive matrix, which can induce a desired cellular behavior. Tailor-made materials for specific applications can be created. Recent approaches to generate dental pulp rely on established materials, such as collagen, polyester, chitosan, or hydroxyapatite. Results after transplantation show soft connective tissue formation and newly generated dentin. For dentin-pulp-complex engineering, aspects including vascularization, cell-matrix interactions, growth-factor incorporation, matrix degradation, mineralization, and contamination control should be considered. Self-assembling peptide hydrogels are an example of a smart material that can be modified to create customized matrices. Rational design of the peptide sequence allows for control of material stiffness, induction of mineral nucleation, or introduction of antibacterial activity. Cellular responses can be evoked by the incorporation of cell adhesion motifs, enzyme-cleavable sites, and suitable growth factors. The combination of inductive scaffold materials with stem cells might optimize the approaches for dentin-pulp complex regeneration.
Topics: Absorbable Implants; Biocompatible Materials; Biomechanical Phenomena; Calcification, Physiologic; Dental Pulp; Dentinogenesis; Equipment Design; Humans; Intercellular Signaling Peptides and Proteins; Neovascularization, Physiologic; Regeneration; Stem Cell Transplantation; Tissue Engineering; Tissue Scaffolds
PubMed: 21677088
DOI: 10.1177/0022034511405326 -
The International Journal of... Feb 1995Based on recent literature, the specific potential of mature pulp cells to differentiate into polarized cells able to elaborate reparative dentin is described. These... (Review)
Review
Based on recent literature, the specific potential of mature pulp cells to differentiate into polarized cells able to elaborate reparative dentin is described. These odontoblast-like cells are distinguished, by morphological criteria, from the other matrix-formative cells involved in non-specific defensive mechanisms of dental pulp. The suitable tissue conditions and the normal cascade of reparative events, allowing initiation of dentinogenesis in sites of amputated pulp, are presented. This is followed by a review of current observations on specific dentinogenic events, induced in various culture systems or in intrapulpal sites of mature teeth by artificial bio-molecules or bio-matrices. Data from these experiments are focused on the role of extracellular matrix molecules and growth factors in acquisition of the odontoblast-like cell phenotype and initiation of reparative dentinogenesis.
Topics: Animals; Cell Differentiation; Dental Pulp; Dentin; Dentinogenesis; Humans; Odontoblasts; Wound Healing
PubMed: 7626418
DOI: No ID Found -
International Journal of Environmental... Jan 2023This study examines 0.6 N-4.8 N as the maximum orthodontic force to be applied to dental pulp and apical NVB on intact and 1-8 mm reduced periodontal-ligament (PDL), in...
This study examines 0.6 N-4.8 N as the maximum orthodontic force to be applied to dental pulp and apical NVB on intact and 1-8 mm reduced periodontal-ligament (PDL), in connection with movement and ischemic, necrotic and resorptive risk. In addition, it examines whether the Tresca finite-element-analysis (FEA) criterion is more adequate for the examination of dental pulp and its apical NVB. Eighty-one (nine patients, with nine models for each patient) anatomically correct models of the periodontium, with the second lower-premolar reconstructed with its apical NVB and dental pulp were assembled, based on X-ray CBCT (cone-beam-computed-tomography) examinations and subjected to 0.6 N, 1.2 N, 2.4 N and 4.8 N of intrusion, extrusion, translation, rotation, and tipping. The Tresca failure criterion was applied, and the shear stress was assessed. Forces of 0.6 N, 1.2 N, and 2.4 N had negligible effects on apical NVB and dental pulp up to 8 mm of periodontal breakdown. A force of 4.8 N was safely applied to apical NVB on the intact periodontium only. Rotation and tipping seemed to be the most invasive movements for the apical NVB. For the dental pulp, only the translation and rotation movements seemed to display a particular risk of ischemia, necrosis, and internal orthodontic-resorption for both coronal (0-8 mm of loss) and radicular pulp (4-8 mm of loss), despite the amount of stress being lower than the MHP. The Tresca failure criterion seems more suitable than other criteria for apical NVB and dental pulp.
Topics: Humans; Bicuspid; Dental Pulp; Computer Simulation; Tooth Movement Techniques; Periodontium; Finite Element Analysis
PubMed: 36673936
DOI: 10.3390/ijerph20021179 -
European Journal of Paediatric Dentistry Dec 2018The literature on "dental stem cells" from 2002 to 2009 is composed of 936 works, mainly basic research articles, 159 reviews, 1 clinical study and only 6 case reports...
The literature on "dental stem cells" from 2002 to 2009 is composed of 936 works, mainly basic research articles, 159 reviews, 1 clinical study and only 6 case reports concerning endodontics and periodontology. After the year 2009 (1) the interest on this research topic has increased leading to 5177 new articles, including 757 reviews on different stem cell types, biomaterials and the possibility of "banking". The 46 clinical trials published in the last 9 years are clinical applications in periodontics and endodontics. However, still no definitive clinical guidelines are available (2,3). Regenerative therapy in endodontics, through the use of dental stem cells, is still an open question (4). The idea of healing the pulp instead of treating it by means of a conventional endodontic therapy is fascinating, but the current experimental protocol is limited to immature permanent teeth with pulp necrosis, which are a minority of endodontic treatments. Since 2005, with the first stem cell bank (Hiroshima University "Three Brackets") (5), attention has also been paid to the creation of private or university centres where it is possible to preserve autologous dental stem cells. In particular, due to the ease and natural availability, the interest is directed to SHED, Stem cells from Human Exfoliated Deciduous teeth (6). SHED are easy to collect, have excellent differentiation potential and, most importantly, are more cost-effective if compared with umbilical cord cells (5). For these reasons in 2008 the Norwegian Institute of Public Health and the University of Bergen started to collect and store the exfoliated teeth of 100,000 children. To date there are several collection centres in the northern emisphere: USA (Bioeden, Stem Save, Store a Tooth), Europe (Bergen, Future Health), India (Stemade biotech), Japan (Teeth Bank, Advanced Center of Tissue Engineering, Hiroshima University and Nogoya University), Taipai (Taipai Medical University), and recently China (National Dental Stem Cells Bank) (7). Dental stem cells are readily and easily available and are a promising resource not just in dentistry but for regenerative medicine in general (8). This is confirmed by the literature, since 25% of papers on stem cells involve the study and dissemination of research on dental tissues-derived stem cells. Currently there are only a few registered clinical trials for stem cell applications in dentistry and the results are still unavailable. To date, there are no dental treatments involving harvested stem cells but this is definitely an emerging science that might lead to important outcomes in the future.
Topics: Dental Care; Dental Pulp; Humans; Stem Cell Transplantation
PubMed: 30567439
DOI: 10.23804/ejpd.2018.19.04.1 -
European Cells & Materials Feb 2019Stem cells are essential for tissue homeostasis and regeneration throughout the lifespan of multicellular organisms. The decline in stem cell function during advanced... (Review)
Review
Stem cells are essential for tissue homeostasis and regeneration throughout the lifespan of multicellular organisms. The decline in stem cell function during advanced age is associated with a reduced regenerative potential of tissues that leads to an increased frequency of diseases. Age-related changes also occur in the dental pulp that represents a reliable model tissue, with high regenerative capability, for studying senescence mechanisms. However, little information is available concerning the effects of ageing on dental stem-cell function. In this mini-review, recent data on how the molecular and functional alterations that accumulate in stem cell populations during ageing result in modifications of dental pulp physiology are discussed. Changes that accumulate during ageing such as how reduction of pulp chamber volume, decreased vascular supply and modifications to the stem cell niches affect stem cell functions and, therefore, dental pulp regenerative potential in response to various stressful agents. Dental pulp cells from aged individuals are still metabolically active and secrete pro-inflammatory and matrix-degrading molecules. Furthermore, miRNAs and exosomes derived from dental pulp stem cells constitute an attractive source of nanovesicles for the treatment of age-related dental pathologies. Further investigation of the epigenetic alterations in dental pulp stem cells, accumulating during ageing, might reveal crucial information for potential stem cell-based therapeutic approaches in the elderly.
Topics: Aging; Animals; Dental Pulp; Exosomes; Humans; Inflammation; Stem Cells; Tooth
PubMed: 30805914
DOI: 10.22203/eCM.v037a11 -
Stem Cell Research & Therapy Feb 2018Human dental pulp stem cells (DPSCs), which have the ability to differentiate into multiple lineages, were recently identified. DPSCs can be collected readily from...
BACKGROUND
Human dental pulp stem cells (DPSCs), which have the ability to differentiate into multiple lineages, were recently identified. DPSCs can be collected readily from extracted teeth and are now considered to be a type of mesenchymal stem cell with higher clonogenic and proliferative potential than bone marrow stem cells (BMSCs). Meanwhile, the treatment of severe bone defects, such as fractures, cancers, and congenital abnormalities, remains a great challenge, and novel bone regenerative techniques are highly anticipated. Several studies have previously shown that 4-(4-methoxyphenyl)pyrido[40,30:4,5]thieno[2,3-b]pyridine-2-carboxamide (TH), a helioxanthin derivative, induces osteogenic differentiation of preosteoblastic and mesenchymal cells. However, the osteogenic differentiation activities of TH have only been confirmed in some mouse cell lines. Therefore, in this study, toward the clinical use of TH in humans, we analyzed the effect of TH on the osteogenic differentiation of DPSCs, and the in-vivo osteogenesis ability of TH-induced DPSCs, taking advantage of the simple transplantation system using cell-sheet technology.
METHODS
DPSCs were obtained from dental pulp of the wisdom teeth of five healthy patients (18-22 years old) and cultured in regular medium and osteogenic medium with or without TH. To evaluate osteogenesis of TH-induced DPSCs in vivo, we transplanted DPSC sheets into mouse calvaria defects.
RESULTS
We demonstrated that osteogenic conditions with TH induce the osteogenic differentiation of DPSCs more efficiently than those without TH and those with bone morphogenetic protein-2. However, regular medium with TH did not induce the osteogenic differentiation of DPSCs. TH induced osteogenesis in both DPSCs and BMSCs, although the gene expression pattern in DPSCs differed from that in BMSCs up to 14 days after induction with TH. Furthermore, we succeeded in bone regeneration in vivo using DPSC sheets with TH treatment, without using any scaffolds or growth factors.
CONCLUSIONS
Our results demonstrate that TH-induced DPSCs are a useful cell source for bone regenerative medicine, and the transplantation of DPSC sheets treated with TH is a convenient scaffold-free method of bone healing.
Topics: Animals; Bone Regeneration; Cell Differentiation; Cells, Immobilized; Dental Pulp; Heterografts; Humans; Lignans; Mice; Mice, Inbred NOD; Mice, SCID; Osteogenesis; Stem Cell Transplantation; Stem Cells
PubMed: 29391049
DOI: 10.1186/s13287-018-0783-7 -
PloS One 2021Bleaching is widely accepted for improving the appearance of discolored teeth; however, patient compliance is affected by bleaching-related complications, especially...
BACKGROUND
Bleaching is widely accepted for improving the appearance of discolored teeth; however, patient compliance is affected by bleaching-related complications, especially bleaching sensitivity. This study aimed to investigate the role of reactive oxygen species (ROS) in cytotoxicity and pain conduction activated by experimental tooth bleaching.
METHODS
Dental pulp stem cells with or without N-acetyl-L-cysteine (NAC), an ROS scavenger, were cultured on the dentin side of the enamel/dentin disc. Subsequently, 15% (90 min) and 40% (30 min) bleaching gels were painted on the enamel surface. Cell viability, intracellular ROS, Ca2+, adenosine triphosphate (ATP), and extracellular ATP levels were evaluated using the Cell Counting Kit-8 assay, 2',7'-dichlorodihydrofluorescein diacetate, CellROX, fura-3AM fluorescence assay, and ATP measurement kit. The rat incisor model was used to evaluate in vivo effects after 0, 1, 3, 7, and 30 days of bleaching. Changes in gene and protein expression of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNFα), transient receptor potential ankyrin 1 (TRPA1), and Pannexin1 (PANX1) in dental pulp stem cells and pulp tissue were detected through RT-PCR, western blotting, and immunofluorescence.
RESULTS
The bleaching gel suppressed dental pulp stem cell viability and extracellular ATP levels and increased intracellular ROS, Ca2+, and intracellular ATP levels. The mRNA and protein expression of IL-6, TNFα, TRPA1, and PANX1 were up-regulated in vitro and in vivo. Furthermore, the 40% gel had a stronger effect than the 15% gel, and NAC ameliorated the gel effects.
CONCLUSIONS
Our findings suggest that bleaching gels induce cytotoxicity and pain conduction in dental pulp stem cells via intracellular ROS, which may provide a potential therapeutic target for alleviating tooth bleaching nociception.
Topics: Adolescent; Adult; Animals; Blotting, Western; Cells, Cultured; Dental Enamel; Dental Pulp; Dentin; Female; Fluorescent Antibody Technique; Humans; Hydrogen Peroxide; Male; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Young Adult
PubMed: 34506603
DOI: 10.1371/journal.pone.0257221 -
Human Molecular Genetics Oct 2017Dental pulp stem cells (DPSC) are a relatively new alternative stem cell source for the study of neurogenetic disorders. DPSC can be obtained non-invasively and... (Review)
Review
Dental pulp stem cells (DPSC) are a relatively new alternative stem cell source for the study of neurogenetic disorders. DPSC can be obtained non-invasively and collected from long-distances remaining viable during transportation. These highly proliferative cells express stem cell markers and retain the ability to differentiate down multiple cell lineages including chondrocytes, adipocytes, osteoblasts, and multiple neuronal cell types. The neural crest origin of DPSC makes them a useful source of primary cells for modeling neurological disorders at the molecular level. In this brief review, we will discuss recent developments in DPSC research that highlight the molecular etiology of DPSC derived neurons and how they may contribute to our understanding of neurogenetic disorders.
Topics: Adipocytes; Adult Stem Cells; Cell Differentiation; Cell Lineage; Cell Proliferation; Cells, Cultured; Chondrocytes; Dental Pulp; Humans; Models, Biological; Neural Crest; Neurons; Osteoblasts
PubMed: 28582499
DOI: 10.1093/hmg/ddx208