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Stem Cell Research & Therapy May 2020Advances in regenerative medicine with stem cells have led to clinical trials. Dental/oral tissues are emerging as promising cellular sources of human mesenchymal stem... (Review)
Review
BACKGROUND
Advances in regenerative medicine with stem cells have led to clinical trials. Dental/oral tissues are emerging as promising cellular sources of human mesenchymal stem cells. Recently, dental tissue-derived cells have been used clinically due to their great potential, easy accessibility, and ability to be obtained via methods with low invasiveness. The aim of this study is to systematically assess the clinical effectiveness of dental cell-mediated therapies compared to current evidence-based methods in human patients.
METHODS
The electronic databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched up to December 2019 for clinical trials. Clinical trials with any intervention using stem cells/cells derived from dental tissue were included.
RESULTS
A total of 815 studies were identified by the electronic search, and 38 articles qualified for full-text evaluation. Finally, 20 studies (10 clinical trials using dental pulp-derived cells, 3 clinical trials using periodontal ligament-derived cells, and 7 studies using gingiva-derived cells) were included in this review. No clinical trials using dental follicle- or apical papilla-derived cells were selected in this review. Dental pulp-derived cells were used in clinical trials for bone regeneration, periodontitis, and dental pulp regeneration. All clinical trials using periodontal ligament-derived cells and gingiva-derived cells were conducted for periodontal disease treatment and gingival augmentation, respectively. Among the 20 selected studies, 16 showed clinical benefits of cell transplantation therapies. In addition, no study reported adverse events that may have been associated with cell transplantation.
CONCLUSIONS
These findings indicate that dental tissue-derived cells would be useful for cell-based regenerative medicine for various diseases.
Topics: Clinical Trials as Topic; Dental Pulp; Gingiva; Humans; Mesenchymal Stem Cells; Periodontal Ligament; Regenerative Medicine
PubMed: 32398041
DOI: 10.1186/s13287-020-01683-x -
Journal of Personalized Medicine Jan 2021Aging is characterized by a progressive decline or loss of physiological functions, leading to increased susceptibility to disease or death. Several aging hallmarks,... (Review)
Review
Aging is characterized by a progressive decline or loss of physiological functions, leading to increased susceptibility to disease or death. Several aging hallmarks, including genomic instability, cellular senescence, and mitochondrial dysfunction, have been suggested, which often lead to the numerous aging disorders. The periodontium, a complex structure surrounding and supporting the teeth, is composed of the gingiva, periodontal ligament, cementum, and alveolar bone. Supportive and protective roles of the periodontium are very critical to sustain life, but the periodontium undergoes morphological and physiological changes with age. In this review, we summarize the current knowledge of molecular and cellular physiological changes in the periodontium, by focusing on soft tissues including gingiva and periodontal ligament.
PubMed: 33477537
DOI: 10.3390/jpm11010058 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Feb 2024Bioactive materials are a type of biomaterials that can generate special biological or chemical reactions on the surface or interface of materials. These reactions can... (Review)
Review
Bioactive materials are a type of biomaterials that can generate special biological or chemical reactions on the surface or interface of materials. These reactions can impact the interaction between tissues and materials, stimulate cell activity, and guide tissue regeneration. In recent years, bioactive materials have been widely used in periodontal tissue regeneration. This review aims to consolidate the definition and characteristics of bioactive materials, as well as summarize their utilization in periodontal tissue regeneration. These findings shed new light on the application of bioactive materials in this field.
Topics: Tissue Engineering; Periodontium; Biocompatible Materials; Wound Healing
PubMed: 38369828
DOI: 10.13345/j.cjb.230234 -
BMC Oral Health Dec 2022Although Vanins are closely related to neutrophil regulation and response to oxidative stress, and play essential roles in inflammatory diseases with clinical...
BACKGROUND
Although Vanins are closely related to neutrophil regulation and response to oxidative stress, and play essential roles in inflammatory diseases with clinical significance, their contribution to periodontitis remains to be determined. This research was designed to assess the expression of Vanins in human gingiva, and to define the relationship between Vanins and periodontitis.
METHODS
Forty-eight patients with periodontitis and forty-two periodontal healthy individuals were enrolled for gingival tissue sample collection. Expression levels of VNN1, VNN2 and VNN3 were evaluated by RT-qPCR and validated in datasets GSE10334 and GSE16134. Western blot and immunohistochemistry identified specific proteins within gingiva. The histopathological changes in gingival sections were investigated using HE staining. Correlations between Vanins and clinical parameters, PD and CAL; between Vanins and inflammation, IL1B; and between Vanins and MPO in periodontitis were investigated by Spearman's correlation analysis respectively. Associations between VNN2 and indicators of neutrophil adherence and migration were further validated in two datasets.
RESULTS
Vanins were at higher concentrations in diseased gingival tissues in both RT-qPCR and dataset analysis (p < 0.01). Assessment using western blot and immunohistochemistry presented significant upregulations of VNN1 and VNN2 in periodontitis (p < 0.05). The higher expression levels of Vanins, the larger the observed periodontal parameters PD and CAL (p < 0.05), and IL1B (p < 0.001). Moreover, positive correlations existed between VNN2 and MPO, and between VNN2 and neutrophil-related indicators.
CONCLUSION
Our study demonstrated upregulation of Vanins in periodontitis and the potential contribution of VNN2 to periodontitis through neutrophils-related pathological processes.
Topics: Humans; Periodontitis; Gingiva; Neutrophils; Inflammation; Proteins
PubMed: 36527111
DOI: 10.1186/s12903-022-02583-7 -
International Journal of Oral Science Oct 2023X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and impaired mineralization...
X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and impaired mineralization of bone and teeth. The clinical manifestations of XLH include a high prevalence of dental abscesses and periodontal disease, likely driven by poorly formed structures of the dentoalveolar complex, including the alveolar bone, cementum, dentin, and periodontal ligament. Our previous studies have demonstrated that sclerostin antibody (Scl-Ab) treatment improves phosphate homeostasis, and increases long bone mass, strength, and mineralization in the Hyp mouse model of XLH. In the current study, we investigated whether Scl-Ab impacts the dentoalveolar structures of Hyp mice. Male and female wild-type and Hyp littermates were injected with 25 mg·kg of vehicle or Scl-Ab twice weekly beginning at 12 weeks of age and euthanized at 20 weeks of age. Scl-Ab increased alveolar bone mass in both male and female mice and alveolar tissue mineral density in the male mice. The positive effects of Scl-Ab were consistent with an increase in the fraction of active (nonphosphorylated) β-catenin, dentin matrix protein 1 (DMP1) and osteopontin stained alveolar osteocytes. Scl-Ab had no effect on the mass and mineralization of dentin, enamel, acellular or cellular cementum. There was a nonsignificant trend toward increased periodontal ligament (PDL) attachment fraction within the Hyp mice. Additional PDL fiber structural parameters were not affected by Scl-Ab. The current study demonstrates that Scl-Ab can improve alveolar bone in adult Hyp mice.
Topics: Mice; Male; Female; Animals; Familial Hypophosphatemic Rickets; Bone and Bones; Tooth; Periodontal Ligament
PubMed: 37813865
DOI: 10.1038/s41368-023-00252-1 -
Journal of Bone and Mineral Research :... Aug 2023Kangfuxin (KFX) shows potential in wound healing, but its role in socket healing is unclear. This research finds increased bone mass, mineralization, and collagen...
Kangfuxin (KFX) shows potential in wound healing, but its role in socket healing is unclear. This research finds increased bone mass, mineralization, and collagen deposition in KFX-treated mice. Mouse bone marrow mesenchymal stem cells, human periodontal ligament stem cells (hPDLSCs), and human dental pulp stem cells (hDPSCs) are treated with KFX under osteogenic induction. RNA-sequencing reveals upregulated chemokine-related genes, with a threefold increase in chemokine (C-C motif) ligand 2 (Ccl2). The conditioned medium (CM) of hPDLSCs and hDPSCs treated with KFX promotes endothelial cell migration and angiogenesis. Ccl2 knockdown abolishes CM-induced endothelial cell migration and angiogenesis, which can be reversed by recombinant CCL2 treatment. KFX-treated mice showed increased vasculature. In conclusion, KFX increases the expression of CCL2 in stem cells, promoting bone formation and mineralization in the extraction socket by inducing endothelial cell angiogenesis. © 2023 American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Animals; Mice; Periodontal Ligament; Up-Regulation; Chemokine CCL2; Stem Cells; Wound Healing; Osteogenesis; Cell Differentiation
PubMed: 37221128
DOI: 10.1002/jbmr.4860 -
Stem Cells and Development Aug 2019Teeth represent a fascinating area of study in regenerative medicine, because of their unique and complex developmental origin. Several types of mesenchymal stem cells... (Review)
Review
Teeth represent a fascinating area of study in regenerative medicine, because of their unique and complex developmental origin. Several types of mesenchymal stem cells (MSCs) have been characterized in the oral cavity, and those derived from the periodontal ligament (PDL) first isolated by our group in 2005, can be expanded in a xeno-free medium preserving morphological features and markers associated with pluripotency. These postnatal MSCs can be easily recovered by noninvasive procedures and cultured. This could facilitate the use of adult stem cells in human clinical regeneration therapy. In this review we summarize the results of our studies describing morphofunctional features, surface markers, and multilineage differentiation capacity in vitro of PDL MSCs obtained in our laboratories. In vivo characterization of PDL stem cell (PDLSC) location and heterogeneity are still lacking. However, we describe studies exploring the potential use of PDLSC to treat both periodontal diseases and regeneration of other tissues. These MSCs may have an advantage in possessing also angiogenetic, immunoregulatory, and anti-inflammatory properties. The secretome of such cells contains several interesting molecules mimicking the effects of the producer cells. We describe some recent studies from our group on the use of conditioned medium from PDL MSCs, and purified extracellular vesicles therein contained, in animal models of experimental autoimmune encephalomyelitis and their potential application to human disease.
Topics: Adult; Animals; Cell Differentiation; Cell Proliferation; Cells, Cultured; Humans; Periodontal Ligament; Regeneration; Regenerative Medicine; Stem Cell Transplantation; Stem Cells
PubMed: 31017047
DOI: 10.1089/scd.2019.0025 -
Cells Mar 2022The oral cavity is the gateway for microorganisms into your body where they disseminate not only to the directly connected respiratory and digestive tracts but also to... (Review)
Review
The oral cavity is the gateway for microorganisms into your body where they disseminate not only to the directly connected respiratory and digestive tracts but also to the many remote organs. Oral microbiota, travelling to the end of the intestine and circulating in our bodies through blood vessels, not only affect a gut microbiome profile but also lead to many systemic diseases. By gathering information accumulated from the era of focal infection theory to the age of revolution in microbiome research, we propose a pivotal role of "leaky gum", as an analogy of "leaky gut", to underscore the importance of the oral cavity in systemic health. The oral cavity has unique structures, the gingival sulcus (GS) and the junctional epithelium (JE) below the GS, which are rarely found anywhere else in our body. The JE is attached to the tooth enamel and cementum by hemidesmosome (HD), which is structurally weaker than desmosome and is, thus, vulnerable to microbial infiltration. In the GS, microbial biofilms can build up for life, unlike the biofilms on the skin and intestinal mucosa that fall off by the natural process. Thus, we emphasize that the GS and the JE are the weakest leaky point for microbes to invade the human body, making the leaky gum just as important as, or even more important than, the leaky gut.
Topics: Gastrointestinal Microbiome; Gingiva; Humans; Intestinal Mucosa; Microbiota; Mouth
PubMed: 35406643
DOI: 10.3390/cells11071079 -
International Journal of Molecular... Jun 2023Periodontal ligament fibroblasts (PdLFs) exert important functions in oral tissue and bone remodeling following mechanical forces, which are specifically applied during...
Periodontal ligament fibroblasts (PdLFs) exert important functions in oral tissue and bone remodeling following mechanical forces, which are specifically applied during orthodontic tooth movement (OTM). Located between the teeth and the alveolar bone, mechanical stress activates the mechanomodulatory functions of PdLFs including regulating local inflammation and activating further bone-remodeling cells. Previous studies suggested growth differentiation factor 15 (GDF15) as an important pro-inflammatory regulator during the PdLF mechanoresponse. GDF15 exerts its effects through both intracrine signaling and receptor binding, possibly even in an autocrine manner. The extent to which PdLFs are susceptible to extracellular GDF15 has not yet been investigated. Thus, our study aims to examine the influence of GDF15 exposure on the cellular properties of PdLFs and their mechanoresponse, which seems particularly relevant regarding disease- and aging-associated elevated GDF15 serum levels. Therefore, in addition to investigating potential GDF15 receptors, we analyzed its impact on the proliferation, survival, senescence, and differentiation of human PdLFs, demonstrating a pro-osteogenic effect upon long-term stimulation. Furthermore, we observed altered force-related inflammation and impaired osteoclast differentiation. Overall, our data suggest a major impact of extracellular GDF15 on PdLF differentiation and their mechanoresponse.
Topics: Humans; Periodontal Ligament; Growth Differentiation Factor 15; Cells, Cultured; Cell Differentiation; Fibroblasts; Inflammation; Tooth Movement Techniques
PubMed: 37373159
DOI: 10.3390/ijms241210011 -
Journal of Applied Biomedicine Dec 2022Periodontal regenerative techniques are performed to accomplish the restitution of soft and hard teeth-supporting tissues that have been lost due to trauma or... (Review)
Review
Periodontal regenerative techniques are performed to accomplish the restitution of soft and hard teeth-supporting tissues that have been lost due to trauma or inflammatory disease. Periodontal membranes are used for these techniques to provide support and a framework for cell growth and tissue regeneration. They act as a temporary and selective barrier to cell proliferation. Easy clinical handling, biomechanical specifications, high biocompatibility, cell-occlusivity, and satisfactory bioresorption rate are essential properties a membrane needs to be effective. The creation and maintenance of a secluded space is also a fundamental rule in periodontal regenerative techniques. The use of barrier membranes in the field of restorative dentistry has progressed toward the use of minimally invasive approaches optimizing wound closure and limiting patient morbidity. This review intends to provide an overview of the major cellular events in the surgical wound and membrane surface. It was also performed to assess, from literature data, the pertinence of using non-resorbable and resorbable membranes for this regenerative purpose. Special attention will be given to collagen membranes.
Topics: Humans; Guided Tissue Regeneration, Periodontal; Membranes, Artificial; Collagen; Periodontal Ligament; Periodontics
PubMed: 36708721
DOI: 10.32725/jab.2022.020