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International Journal of Oral Science Oct 2022Maintaining the stemness of the transplanted stem cell spheroids in an inflammatory microenvironment is challenging but important in regenerative medicine. Direct...
Maintaining the stemness of the transplanted stem cell spheroids in an inflammatory microenvironment is challenging but important in regenerative medicine. Direct delivery of stem cells to repair periodontal defects may yield suboptimal effects due to the complexity of the periodontal inflammatory environment. Herein, stem cell spheroid is encapsulated by interfacial assembly of metal-phenolic network (MPN) nanofilm to form a stem cell microsphere capsule. Specifically, periodontal ligament stem cells (PDLSCs) spheroid was coated with Fe/tannic acid coordination network to obtain spheroid@[Fe-TA] microcapsules. The formed biodegradable MPN biointerface acted as a cytoprotective barrier and exhibited antioxidative, antibacterial and anti-inflammatory activities, effectively remodeling the inflammatory microenvironment and maintaining the stemness of PDLSCs. The stem cell microencapsulation proposed in this study can be applied to multiple stem cells with various functional metal ion/polyphenol coordination, providing a simple yet efficient delivery strategy for stem cell stemness maintenance in an inflammatory environment toward a better therapeutic outcome.
Topics: Anti-Bacterial Agents; Capsules; Cell Differentiation; Cell Encapsulation; Cells, Cultured; Ferric Compounds; Osteogenesis; Periodontal Ligament; Polyphenols; Stem Cells; Tannins
PubMed: 36216801
DOI: 10.1038/s41368-022-00198-w -
Journal of Periodontology May 2023The resolution of inflammation is an active process mediated by specialized lipid mediators called lipoxins and resolvins. Periodontal ligament fibroblasts (PDLFs) play...
BACKGROUND
The resolution of inflammation is an active process mediated by specialized lipid mediators called lipoxins and resolvins. Periodontal ligament fibroblasts (PDLFs) play a significant role in periodontal regeneration. The purpose of the current study was to determine the impact of resolvin D1 (RvD1) on human PDLF cell wound healing and proliferation, receptor expression (G-protein-coupled receptor 32 [GPR32] and formyl peptide receptor 2 [ALX/FPR2]), and cytokine expression and release.
METHODS
PDLFs were stimulated with interleukin-1β (IL-1β) (500 pg/ml) with and without RvD1 (100 nM). RvD1 receptor expression was determined by quantitative real-time polymerase chain reaction (qPCR), immunofluorescence microscopy, and fluorescence-activated cell sorting. Wound closure was measured by a scratch assay, and proliferation was determined by bromodeoxyuridine incorporation. Interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1, cyclooxygenase-2, matrix metalloproteinases-1, -2, and -3 (MMP-1, -2, and -3), tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1 and -2), prostaglandin E2, and osteoprotegerin (OPG) gene expression and production were measured using qPCR and Western blotting, multiplex immunoassay, and enzyme-linked immunosorbent assay.
RESULTS
PDLF expressed GPR32 and ALX/FPR2. RvD1 reversed IL-1β-induced inhibition of wound healing and proliferation of PDLF. IL-1β also induced the production of proinflammatory cytokines and MMPs. This effect was reversed by RvD1. RvD1 reversed IL-1β-induced inhibition of TIMP-1, TIMP-2, and OPG.
CONCLUSION
The data suggested that RvD1 has a pro-wound healing, proliferative, and anti-inflammatory impact on the PDLF that favors periodontal regeneration.
Topics: Humans; Tissue Inhibitor of Metalloproteinase-1; Periodontal Ligament; Inflammation; Docosahexaenoic Acids; Fibroblasts; Cytokines
PubMed: 36416879
DOI: 10.1002/JPER.22-0462 -
Frontiers in Immunology 2022Periapical lesions are infectious diseases that occur in the apical region of teeth. They result in the destruction of alveolar bone and are usually accompanied by... (Review)
Review
Periapical lesions are infectious diseases that occur in the apical region of teeth. They result in the destruction of alveolar bone and are usually accompanied by swelling, pain, and possible systemic impacts. A complex interaction between pathogens and the host immune system determines the development, progression, and outcome of periapical lesions. The lesions, if not treated promptly, may cause resorption of bone tissue, destruction of the periodontal ligament, and loss of the affected teeth, all of which can severely worsen the quality of life of patients, often at considerable economic cost to both patients and medical organizations. Macrophages are a group of heterogeneous cells that have many roles in the development of infections, destruction and reconstruction of bone tissues, and microbe-host interactions. However, the differential and comprehensive polarization of macrophages complicates the understanding of the regulatory mechanism of periapical lesion progression. This report provides a comprehensive review of recent advances in our knowledge of the potential role of macrophages in determining the turnover of human periapical lesions. For example, macrophage differentiation might indicate whether the lesions are stable or progressing while the extent of bacteria invasion could regulate the differentiation and function of macrophages involved in the periapical lesion. In addition, alternative strategies for the treatment of apical periodontitis are discussed.
Topics: Humans; Macrophages; Periapical Periodontitis; Periodontal Ligament; Quality of Life
PubMed: 36131939
DOI: 10.3389/fimmu.2022.949102 -
Medicina Oral : Organo Oficial de La... 2003For many years the diagnosis of Periodontal Disease has been based on clinical and radiographic methods. Other more recent methods have the objective of studying the... (Review)
Review
For many years the diagnosis of Periodontal Disease has been based on clinical and radiographic methods. Other more recent methods have the objective of studying the inflammatory response of the host. That way, immunologic and biological methods determine the free mediators in the periodontal infection. The components of the gingivo-crevicular liquid or fluid are used to identify or to diagnose the active disease, to anticipate the risk of acquiring the disease and to determine its progress. For it to be clinically useful important changes should be registered the way a specific site turns active or that a previously disease affected site improves its conditions as a result of periodontal therapy. The response of the neutrophillic granulocytes play an important role in the detection of Periodontal Disease. The unspecific defense system in the gingivo-crevicular fluid can be determined through cytokines and/or interleukines that serve to identify sites at risk on the patient. In Periodontal Disease, the cytokines are not only defense mediators of the gingival sulcus fluid, but are also an indicator of tissue destruction. The liberation of high levels of lysosomal enzymes by neutrophils, proteolytic enzymes as the collagenases, or intercytoplasmatic enzymes as dehydrogenase lactate and aspartate amino transferase can equally help monitor the progress of the Periodontal Disease.
Topics: Biomarkers; Enzymes; Gingival Crevicular Fluid; Humans; Periodontal Diseases; Periodontal Ligament
PubMed: 14595256
DOI: No ID Found -
Trends in Cell Biology Dec 2010Teeth exhibit limited repair in response to damage, and dental pulp stem cells probably provide a source of cells to replace those damaged and to facilitate repair. Stem... (Review)
Review
Teeth exhibit limited repair in response to damage, and dental pulp stem cells probably provide a source of cells to replace those damaged and to facilitate repair. Stem cells in other parts of the tooth, such as the periodontal ligament and growing roots, play more dynamic roles in tooth function and development. Dental stem cells can be obtained with ease, making them an attractive source of autologous stem cells for use in restoring vital pulp tissue removed because of infection, in regeneration of periodontal ligament lost in periodontal disease, and for generation of complete or partial tooth structures to form biological implants. As dental stem cells share properties with mesenchymal stem cells, there is also considerable interest in their wider potential to treat disorders involving mesenchymal (or indeed non-mesenchymal) cell derivatives, such as in Parkinson's disease.
Topics: Animals; Dental Pulp; Humans; Mesenchymal Stem Cells; Periodontal Ligament; Regeneration; Stem Cells; Tooth
PubMed: 21035344
DOI: 10.1016/j.tcb.2010.09.012 -
Stem Cell Research & Therapy Feb 2023Periodontitis is a high prevalence oral disease which damages both the hard and soft tissue of the periodontium, resulting in tooth mobility and even loss. Existing... (Review)
Review
Periodontitis is a high prevalence oral disease which damages both the hard and soft tissue of the periodontium, resulting in tooth mobility and even loss. Existing clinical treatment methods cannot fully achieve periodontal tissue regeneration; thus, due to the unique characteristics of mesenchymal stem cells (MSCs), they have become the focus of attention and may be the most promising new therapy for periodontitis. Accumulating evidence supports the view that the role of MSCs in regenerative medicine is mainly achieved by the paracrine pathway rather than direct proliferation and differentiation at the injured site. Various cells release lipid-enclosed particles known as extracellular vesicles (EVs), which are rich in bioactive substances. In periodontitis, EVs play a pivotal role in regulating the biological functions of both periodontal tissue cells and immune cells, as well as the local microenvironment, thereby promoting periodontal injury repair and tissue regeneration. As a cell-free therapy, MSCs-derived extracellular vesicles (MSC-EVs) have some preponderance on stability, immune rejection, ethical supervision, and other problems; therefore, they may have a broad clinical application prospect. Herein, we gave a brief introduction to MSC-EVs and focused on their mechanisms and clinical application in periodontal regeneration.
Topics: Humans; Extracellular Vesicles; Periodontium; Periodontitis; Periodontal Ligament; Mesenchymal Stem Cells
PubMed: 36782259
DOI: 10.1186/s13287-023-03242-6 -
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 -
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