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1.
Dent Mater ; 37(5): 816-831, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33676764

RESUMO

OBJECTIVES: The success of a dental implant system not only depends on appropriate osseointegration at the bone-implant interface, but also on robust soft-tissue integration (STI)/muco-integration at the transmucosal region. However, numerous studies have reported that the STI quality of conventional smooth and bio-inert titanium-based transmucosal components is significantly inferior to that of natural teeth, which may compromise the long-term success of implant restorations. In this review article, we discuss the structural and histological characteristics of peri-implant tissues; compare the roles of various cells residing in the transmucosal region and explore the material-based challenges that must be addressed to achieve early establishment and long-term maintenance of STI. METHODS: This extensive review article critically compares and contrasts the findings from articles published in the domain of 'soft-tissue integration around Ti dental implants'. RESULTS: Histological characteristics, including poorer epithelial attachment and absence of direct collagen-implant/abutment integration, are responsible for the inferior STI strength around dental implants/abutments. Furthermore, various cellular functions during STI establishment and maturation at the abutment-mucosa interface must be modulated to achieve early STI. Moreover, we discuss and detail the challenges of achieving robust STI, including the presence of oral bacterial milieu, as well as material and corrosion related issues. Finally, research challenges towards achieving and maintaining robust STI are discussed, targeting the future directions to enhance the long-term survival of implant restorations. SIGNIFICANCE: Based on its histological characteristics, STI on current implant/abutment surfaces is suboptimal compared to the periodontal attachment found at teeth, making implants potentially more susceptible to disease initiation and progression. To obtain stable STI at the trasmucosal region, it is essential for future studies to design customized implant systems, with enhanced surface bioactivity and tailorable therapeutic capacity, which can improve the long-term success of implant restorations, especially in compromised conditions.


Assuntos
Implantes Dentários , Dente Suporte , Implantação Dentária Endo-Óssea , Planejamento de Prótese Dentária , Osseointegração , Titânio
2.
J Clin Immunol ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33534079

RESUMO

Phosphoglucomutase 3 (PGM3) deficiency is a rare congenital disorder of glycosylation. Most of patients with autosomal recessive hypomorphic mutations in PGM3 encoding for phosphoglucomutase 3 present with eczema, skin and lung infections, elevated serum IgE, as well as neurological and skeletal features. A few PGM3-deficient patients suffer from a more severe disease with nearly absent T cells and severe skeletal dysplasia. We performed targeted next-generation sequencing on two kindred to identify the underlying genetic etiology of a severe combined immunodeficiency with developmental defect. We report here two novel homozygous missense variants (p.Gly359Asp and p.Met423Thr) in PGM3 identified in three patients from two unrelated kindreds with severe combined immunodeficiency, neurological impairment, and skeletal dysplasia. Both variants segregated with the disease in the two families. They were predicted to be deleterious by in silico analysis. PGM3 enzymatic activity was found to be severely impaired in primary fibroblasts and Epstein-Barr virus immortalized B cells from the kindred carrying the p.Met423Thr variant. Our findings support the pathogenicity of these two novel variants in severe PGM3 deficiency.

3.
Acta Biomater ; 124: 33-49, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33444803

RESUMO

Osseointegration at the bone-implant interface and soft tissue integration (STI) at the trans-mucosal region are crucial for the long-term success of dental implants, especially in compromised patient conditions. The STI quality of conventional smooth and bio-inert titanium-based implants is inferior to that of natural tissue (i.e. teeth), and hence various surface modifications have been suggested. This review article compares and contrasts the various modification strategies (physical, chemical and biological) utilized to enhance STI of Ti implants. It also details the STI challenges associated with conventional Ti-based implants, current surface modification strategies and cutting-edge nano-engineering solutions. The topographical, biological and therapeutic advances achievable via electrochemically anodized Ti implants with TiO2 nanotubes/nanopores are highlighted. Finally, the status and future directions of such nano-engineered implants is discussed, with emphasis on bridging the gap between research and clinical translation.

4.
J Appl Oral Sci ; 28: e20200170, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32997085

RESUMO

METHODOLOGY: Gingival conditions and tooth sensitivity of young patients with amelogenesis imperfecta lack in depth studies. This case-control study aimed to compare (1) the gingival inflammation, the presence of enamel defects, and tooth sensitivity in young patients with and without amelogenesis imperfecta and (2) to investigate if any difference exists between subtypes of amelogenesis imperfecta. We compared forty-two participants with amelogenesis imperfecta with forty-two controls matched for age, gender, and the number of examined sites. Based on interview, clinical examination, and intraoral photography, we collected data on periodontal conditions, enamel defects and the presence of tooth sensitivity. Comparison tests were performed to investigate if any difference existed between cases and controls; and among cases, between the different subtypes of amelogenesis imperfecta. We performed a post-hoc analysis for any significant difference observed. RESULTS: We observed more gingival inflammation, enamel defects and tooth sensitivity among cases (all p<0.05). Participants with hypocalcified amelogenesis imperfecta had more gingival inflammation, enamel defects, and tooth sensitivity than patients with the hypoplastic and hypomature subtypes (all p<0.05). After adjustment for dental plaque, gingival inflammation was associated with the presence of amelogenesis imperfecta (OR (95%CI) = 1.14 (1.05; 1.24). p<0.01). CONCLUSION: Gingival inflammation, enamel defect and tooth sensitivity are more frequently observed among young patients with amelogenesis imperfecta, and more specifically among children with the hypocalcified subtype.

5.
J Exp Med ; 217(11)2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-32812031

RESUMO

Epstein-Barr virus (EBV) preferentially infects epithelial cells and B lymphocytes and sometimes T and NK lymphocytes. Persistence of EBV-infected cells results in severe lymphoproliferative disorders (LPDs). Diagnosis of EBV-driven T or NK cell LPD and chronic active EBV diseases (CAEBV) is difficult, often requiring biopsies. Herein, we report a flow-FISH cytometry assay that detects cells expressing EBV-encoded small RNAs (EBERs), allowing rapid identification of EBV-infected cells among PBMCs. EBV-infected B, T, and/or NK cells were detectable in various LPD conditions. Diagnosis of CAEBV in 22 patients of Caucasian and African origins was established. All exhibited circulating EBV-infected T and/or NK cells, highlighting that CAEBV is not restricted to native American and Asian populations. Proportions of EBV-infected cells correlated with blood EBV loads. We showed that EBV-infected T cells had an effector memory activated phenotype, whereas EBV-infected B cells expressed plasma cell differentiation markers. Thus, this method achieves accurate and unambiguous diagnoses of different forms of EBV-driven LPD and represents a powerful tool to study their pathophysiological mechanisms.

6.
Science ; 369(6500): 202-207, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32647003

RESUMO

Immunodeficiency often coincides with hyperactive immune disorders such as autoimmunity, lymphoproliferation, or atopy, but this coincidence is rarely understood on a molecular level. We describe five patients from four families with immunodeficiency coupled with atopy, lymphoproliferation, and cytokine overproduction harboring mutations in NCKAP1L, which encodes the hematopoietic-specific HEM1 protein. These mutations cause the loss of the HEM1 protein and the WAVE regulatory complex (WRC) or disrupt binding to the WRC regulator, Arf1, thereby impairing actin polymerization, synapse formation, and immune cell migration. Diminished cortical actin networks caused by WRC loss led to uncontrolled cytokine release and immune hyperresponsiveness. HEM1 loss also blocked mechanistic target of rapamycin complex 2 (mTORC2)-dependent AKT phosphorylation, T cell proliferation, and selected effector functions, leading to immunodeficiency. Thus, the evolutionarily conserved HEM1 protein simultaneously regulates filamentous actin (F-actin) and mTORC2 signaling to achieve equipoise in immune responses.


Assuntos
Actinas/metabolismo , Citocinas/biossíntese , Síndromes de Imunodeficiência/genética , Transtornos Linfoproliferativos/genética , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Proteínas de Membrana/fisiologia , Fator 1 de Ribosilação do ADP/metabolismo , Linfócitos T CD4-Positivos/imunologia , Proliferação de Células , Humanos , Síndromes de Imunodeficiência/imunologia , Transtornos Linfoproliferativos/imunologia , Proteínas de Membrana/genética , Linhagem , Fosforilação , Família de Proteínas da Síndrome de Wiskott-Aldrich/química , Família de Proteínas da Síndrome de Wiskott-Aldrich/metabolismo
7.
Heliyon ; 6(6): e04246, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32617420

RESUMO

Background: Basic fibroblast growth factor (bFGF) regulates cell proliferation, migration, and differentiation in various cell types. The aim of the present study was to determine the bFGF target genes in stem cells isolated from human exfoliated deciduous teeth (SHEDs). Methods: Cells were isolated from pulp tissue obtained from exfoliated deciduous teeth. Mesenchymal stem cell surface markers and the differentiation potential toward adipogenic and neurogenic lineages were characterized. The bFGF-treated SHED transcriptome was examined using a high throughput RNA sequencing technique. The mRNA and protein expression of selected genes were evaluated using real-time polymerase chain reaction and immunofluorescence staining, respectively. Cell cycle analysis was performed by flow cytometry. The colony forming unit number was also examined. Results: The isolated cells expressed CD44, CD90, CD105, but not CD45. The upregulation of adipogenic and neurogenic marker genes was observed after culturing cells in the appropriate induction medium. Transcriptome analysis of the bFGF treated cells revealed that the upregulated genes were in the cell cycle related pathways, while the downregulated genes were in the extracellular matrix related pathways. Correspondingly, bFGF induced MKI67 mRNA expression and Ki67 protein expression. Furthermore, bFGF treatment significantly decreased the G0/G1, but increased the G2/M, population in SHEDs. Colony formation was markedly increased in the bFGF treated group and was attenuated by pretreating the cells with FGFR or PI3K inhibitors. Conclusion: bFGF controls cell cycle progression in SHEDs. Thus, it can be used to amplify cell number to obtain the amount of cells required for regenerative treatments.

9.
J. appl. oral sci ; 28: e20200170, 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS, BBO - Odontologia | ID: biblio-1134781

RESUMO

Abstract Gingival conditions and tooth sensitivity of young patients with amelogenesis imperfecta lack in depth studies. This case-control study aimed to compare (1) the gingival inflammation, the presence of enamel defects, and tooth sensitivity in young patients with and without amelogenesis imperfecta and (2) to investigate if any difference exists between subtypes of amelogenesis imperfecta. Methodology We compared forty-two participants with amelogenesis imperfecta with forty-two controls matched for age, gender, and the number of examined sites. Based on interview, clinical examination, and intraoral photography, we collected data on periodontal conditions, enamel defects and the presence of tooth sensitivity. Comparison tests were performed to investigate if any difference existed between cases and controls; and among cases, between the different subtypes of amelogenesis imperfecta. We performed a post-hoc analysis for any significant difference observed. Results We observed more gingival inflammation, enamel defects and tooth sensitivity among cases (all p<0.05). Participants with hypocalcified amelogenesis imperfecta had more gingival inflammation, enamel defects, and tooth sensitivity than patients with the hypoplastic and hypomature subtypes (all p<0.05). After adjustment for dental plaque, gingival inflammation was associated with the presence of amelogenesis imperfecta (OR (95%CI) = 1.14 (1.05; 1.24). p<0.01). Conclusion Gingival inflammation, enamel defect and tooth sensitivity are more frequently observed among young patients with amelogenesis imperfecta, and more specifically among children with the hypocalcified subtype.

10.
J Exp Med ; 216(12): 2800-2818, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31537641

RESUMO

Infection of T cells by Epstein-Barr virus (EBV) causes chronic active EBV infection (CAEBV) characterized by T cell lymphoproliferative disorders (T-LPD) of unclear etiology. Here, we identified two homozygous biallelic loss-of-function mutations in PIK3CD and TNFRSF9 in a patient who developed a fatal CAEBV. The mutation in TNFRSF9 gene coding CD137/4-1BB, a costimulatory molecule expressed by antigen-specific activated T cells, resulted in a complete loss of CD137 expression and impaired T cell expansion toward CD137 ligand-expressing cells. Isolated as observed in one sibling, CD137 deficiency resulted in persistent EBV-infected T cells but without clinical manifestations. The mutation in PIK3CD gene that encodes the catalytic subunit p110δ of the PI3K significantly reduced its kinase activity. Deficient T cells for PIK3CD exhibited reduced AKT signaling, while calcium flux, RAS-MAPK activation, and proliferation were increased, suggestive of an imbalance between the PLCγ1 and PI3K pathways. These skewed signals in T cells may sustain accumulation of EBV-infected T cells, a process controlled by the CD137-CD137L pathway, highlighting its critical role in immunity to EBV.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/deficiência , Infecções por Vírus Epstein-Barr/etiologia , Herpesvirus Humano 4/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/deficiência , Ativação Viral/genética , Ativação Viral/imunologia , Classe I de Fosfatidilinositol 3-Quinases/química , Suscetibilidade a Doenças , Infecções por Vírus Epstein-Barr/diagnóstico , Mutação em Linhagem Germinativa , Histocitoquímica , Homozigoto , Humanos , Imunofenotipagem , Mutação com Perda de Função , Ativação Linfocitária , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/metabolismo , Modelos Moleculares , Linhagem , Fosfolipase C gama/metabolismo , Conformação Proteica , Proteínas Proto-Oncogênicas c-akt , Proteínas Quinases S6 Ribossômicas/metabolismo , Análise de Sequência de DNA , Transdução de Sinais , Relação Estrutura-Atividade , Linfócitos T/virologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/química
11.
Am J Med Genet A ; 179(10): 1913-1981, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31468724

RESUMO

Dental anomalies occur frequently in a number of genetic disorders and act as major signs in diagnosing these disorders. We present definitions of the most common dental signs and propose a classification usable as a diagnostic tool by dentists, clinical geneticists, and other health care providers. The definitions are part of the series Elements of Morphology and have been established after careful discussions within an international group of experienced dentists and geneticists. The classification system was elaborated in the French collaborative network "TÊTECOU" and the affiliated O-Rares reference/competence centers. The classification includes isolated and syndromic disorders with oral and dental anomalies, to which causative genes and main extraoral signs and symptoms are added. A systematic literature analysis yielded 408 entities of which a causal gene has been identified in 79%. We classified dental disorders in eight groups: dental agenesis, supernumerary teeth, dental size and/or shape, enamel, dentin, dental eruption, periodontal and gingival, and tumor-like anomalies. We aim the classification to act as a shared reference for clinical and epidemiological studies. We welcome critical evaluations of the definitions and classification and will regularly update the classification for newly recognized conditions.


Assuntos
Terminologia como Assunto , Anormalidades Dentárias/classificação , Anormalidades Dentárias/genética , Dente/patologia , Pontos de Referência Anatômicos , Predisposição Genética para Doença , Humanos , Cooperação Internacional , Mucosa Bucal/patologia , Radiografia Panorâmica , Dente/diagnóstico por imagem , Anormalidades Dentárias/diagnóstico por imagem , Dente Supranumerário/diagnóstico por imagem
12.
Sleep Med ; 58: 123-129, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31146124

RESUMO

BACKGROUND: Sleep-disordered breathing (SDB), including obstructive sleep apnea syndrome, is often underestimated because it requires a burdensome test (ie, polysomnography) to ensure diagnosis. To improve polysomnography referral, it is of utmost importance to validate efficient alternative screening tools. This study aimed to provide a translation and a cross-cultural validation of the Pediatric Sleep Questionnaire (PSQ) into French to obtain an easy-to-use and reliable screening tool. The psychometric properties of the French version were also determined. METHODS: The process of cross-cultural adaptation was carried out following these steps: forward-backward translation, evaluation by an expert committee, and pretesting of the pre-final version. Reliability of the French-PSQ version was assessed by Cronbach's alpha coefficients and Spearman's correlation on a convenient sample of 201 children (aged between 2 and 17 years). Construct validity was determined by factor analysis of principal components. RESULTS: Internal consistency was within an adequate range for all subscales: 0.711 for snoring, 0.559 for sleepiness, 0.682 for behavioral problems, and 0.776 for the whole questionnaire. Spearman's correlation analysis comparing questionnaires administered two weeks apart showed good correlation coefficients for all subscales (snoring: 0.642, sleepiness: 0.846, behavioral problems: 0.780, and entire SRBD scale: 0.835). Factor analysis performed to assess the structure of the French-SRBD scale confirmed the same four factors described in the original questionnaire ("breathing," "behavior," "sleepiness," and "other"). CONCLUSION: The French version of the PSQ has been successfully cross-culturally adapted and showed good psychometric properties, suggesting that it is useful as a tool to screen sleep-disordered breathing in French-speaking children.


Assuntos
Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/fisiopatologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Adolescente , Criança , Pré-Escolar , Comparação Transcultural , Estudos Transversais , Análise Fatorial , Feminino , França/epidemiologia , Humanos , Masculino , Polissonografia/métodos , Prevalência , Comportamento Problema/psicologia , Psicometria/instrumentação , Reprodutibilidade dos Testes , Respiração , Síndromes da Apneia do Sono/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Sonolência , Ronco/epidemiologia , Inquéritos e Questionários , Tradução
13.
Stem Cells Int ; 2019: 9310318, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30766608

RESUMO

A large array of therapeutic procedures is available to treat cartilage disorders caused by trauma or inflammatory disease. Most are invasive and may result in treatment failure or development of osteoarthritis due to extensive cartilage damage from repeated surgery. Despite encouraging results of early cell therapy trials that used chondrocytes collected during arthroscopic surgery, these approaches have serious disadvantages, including morbidity associated with cell harvesting and low predictive clinical outcomes. To overcome these limitations, adult stem cells derived from bone marrow and subsequently from other tissues are now considered as preferred sources of cells for cartilage regeneration. Moreover, with new evidence showing that the choice of cell source is one of the most important factors for successful cell therapy, there is growing interest in neural crest-derived cells in both the research and clinical communities. Neural crest-derived cells such as nasal chondrocytes and oral stem cells that exhibit chondrocyte-like properties seem particularly promising in cartilage repair. Here, we review the types of cells currently available for cartilage cell therapy, including articular chondrocytes and various mesenchymal stem cells, and then highlight recent developments in the use of neural crest-derived chondrocytes and oral stem cells for repair of cartilage lesions.

14.
Front Oncol ; 9: 1374, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31921638

RESUMO

Background: B-cell acute lymphoblastic leukemia associated with t(5;14)(q31;q32); IGH-IL3 is an exceptional cause of eosinophilia. The IGH enhancer on 14q32 is juxtaposed to the IL3 gene on 5q31, leading to interleukin-3 overproduction and release of mature eosinophils in the blood. Clinical, biological and outcome data are extremely scarce in the literature. Except for eosinophilia, no relevant common feature has been highlighted in these patients. However, it has been classified as a distinct entity in the World Health Organization classification. Cases Presentation: Eight patients with t(5;14)(q31;q32) treated by French or Austrian protocols were retrospectively enrolled. Array comparative genomic hybridization, multiplex ligation-dependent probe amplification or genomic PCR search for IKZF1 deletion were performed in 7. Sixteen patients found through an exhaustive search in the literature were also analyzed. For those 24 patients, median age at diagnosis is 14.3 years with a male predominance (male to female ratio = 5). Eosinophilia-related symptoms are common (neurologic in 26%, thromboembolic in 26% or pulmonary in 50%). Median white blood cells count is high (72 × 109/L) and linked to eosinophilia (median: 32 × 109/L). Peripheral blasts are present at a low level or absent (median: 0 × 109/L; range: 0-37 × 109/L). Bone marrow morphology is marked by a low blast infiltration (median: 42%). We found an IKZF1 deletion in 5 out of 7 analyzable patients Outcome data are available for 14 patients (median follow-up: 28 months): 8 died and 6 are alive in complete remission. Some of these features are concordant with those seen in patients with other IGH-rearranged B-cell acute lymphoblastic leukemias: young age at onset, male sex, low blast count, high incidence of IKZF1 deletion and intermediate prognosis. Conclusion: Based on shared epidemiological and biological features, B-cell acute lymphoblastic leukemia with t(5;14)(q31;q32) is a peculiar subset of IGH-rearranged B-cell acute lymphoblastic leukemia with an intermediate prognosis and particular clinical features related to eosinophilia.

15.
R Soc Open Sci ; 5(10): 180864, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30473835

RESUMO

Interleukin 6 (IL-6) plays various roles including stem cell regulation. The present study investigated the effect of IL-6 on cell proliferation, colony forming unit ability, stem cell marker expression and differentiation ability in stem cells isolated from human exfoliated deciduous teeth (SHEDs). We reported that the isolated cells from dental pulp tissues for deciduous teeth expressed CD44, CD90 and CD105 but not CD45. These cells were able to differentiate into osteoblasts, adipocytes and neuronal-like cells. IL-6 treatment resulted in the significant increase of NANOG, SOX2 and REX1 mRNA expression. However, IL-6 had no effect on cell proliferation and colony forming unit ability. IL-6 did not alter adipogenic and neurogenic differentiation potency. IL-6 supplementation in osteogenic medium led to a significant increase of mineralization. Furthermore, IL-6 upregulated ALP, ANKH and PIT1 mRNA levels. In conclusion, IL-6 participates in the regulation of pluripotent marker expression and is also involved in mineralization process of SHEDs. Hence, IL-6 could be employed as a supplementary substance in culture medium to maintain stemness and to induce osteogenic induction in SHEDs for future regenerative cell therapy.

16.
BMC Oral Health ; 18(1): 108, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29907114

RESUMO

BACKGROUND: Hereditary enamel defect diseases are regrouped under the name "Amelogenesis Imperfecta" (AIH). Both dentitions are affected. Clinical expression is heterogeneous and varies between patients. Mutations responsible for this multigene disease may alter various genes and the inheritance can be either autosomal dominant or recessive, or X-linked. Until now, no therapeutic consensus has emerged for this rare disease. CASE PRESENTATION: The purpose of this article was to report treatments of AIH patients from childhood to early adulthood. Treatment of three patients of 3, 8 16 years old are described. Each therapeutic option was discussed according to patients' age and type of enamel alteration. Paediatric crowns and resin based bonding must be preferred in primary teeth. In permanent teeth, non-invasive or minimally invasive dentistry should be the first choice in order to follow a therapeutic gradient from the less invasive options to prosthodontic treatments. CONCLUSION: Functional and aesthetic issues require patients to be treated; this clinical care should be provided as early as possible to enable a harmonious growth of the maxillofacial complex and to prevent pain.


Assuntos
Amelogênese Imperfeita/terapia , Dente Decíduo/anormalidades , Adolescente , Criança , Pré-Escolar , Coroas , Colagem Dentária , Restauração Dentária Permanente , Dentição Permanente , Feminino , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Ortodontia Corretiva
17.
Biomaterials ; 172: 41-53, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29715594

RESUMO

Tissue engineering therapies using adult stem cells derived from neural crest have sought accessible tissue sources of these cells because of their potential pluripotency. In this study, the gingiva and oral mucosa and their associated stem cells were investigated. Biopsies of these tissues produce neither scarring nor functional problems and are relatively painless, and fresh tissue can be obtained readily during different chairside dental procedures. However, the embryonic origin of these cells needs to be clarified, as does their evolution from the perinatal period to adulthood. In this study, the embryonic origin of gingival fibroblasts were determined, including gingival stem cells. To do this, transgenic mouse models were used to track neural crest derivatives as well as cells derived from paraxial mesoderm, spanning from embryogenesis to adulthood. These cells were compared with ones derived from abdominal dermis and facial dermis. Our results showed that gingival fibroblasts are derived from neural crest, and that paraxial mesoderm is involved in the vasculogenesis of oral tissues during development. Our in vitro studies revealed that the neuroectodermal origin of gingival fibroblasts (or gingival stem cells) endows them with multipotential properties as well as a specific migratory and contractile phenotype which may participate to the scar-free properties of the oral mucosa. Together, these results illustrate the high regenerative potential of neural crest-derived stem cells of the oral mucosa, including the gingiva, and strongly support their use in cell therapy to regenerate tissues with impaired healing.


Assuntos
Mesoderma/metabolismo , Mucosa Bucal/efeitos dos fármacos , Crista Neural/metabolismo , Transplantes/metabolismo , Cicatrização/efeitos dos fármacos , Animais , Técnicas de Cultura de Células , Diferenciação Celular , Terapia Baseada em Transplante de Células e Tecidos/métodos , Fibroblastos/citologia , Fibroblastos/enzimologia , Gengiva/citologia , Humanos , Camundongos , Modelos Animais , Morfogênese , Mucosa Bucal/citologia , Células-Tronco Neurais/metabolismo , Regeneração
18.
PLoS One ; 13(1): e0190014, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29370163

RESUMO

BACKGROUND: Calcium silicate-based cements are biomaterials with calcium oxide and carbonate filler additives. Their properties are close to those of dentin, making them useful in restorative dentistry and endodontics. The aim of this study was to evaluate the in vitro biological effects of two such calcium silicate cements, Biodentine (BD) and Bioroot (BR), on dental stem cells in both direct and indirect contact models. The two models used aimed to mimic reparative dentin formation (direct contact) and reactionary dentin formation (indirect contact). An original aspect of this study is the use of an interposed thin agarose gel layer to assess the effects of diffusible components from the materials. RESULTS: The two biomaterials were compared and did not modify dental pulp stem cell (DPSC) proliferation. BD and BR showed no significant cytotoxicity, although some cell death occurred in direct contact. No apoptosis or inflammation induction was detected. A striking increase of mineralization induction was observed in the presence of BD and BR, and this effect was greater in direct contact. Surprisingly, biomineralization occurred even in the absence of mineralization medium. This differentiation was accompanied by expression of odontoblast-associated genes. Exposure by indirect contact did not stimulate the induction to such a level. CONCLUSION: These two biomaterials both seem to be bioactive and biocompatible, preserving DPSC proliferation, migration and adhesion. The observed strong mineralization induction through direct contact highlights the potential of these biomaterials for clinical application in dentin-pulp complex regeneration.


Assuntos
Materiais Dentários , Polpa Dentária/efeitos dos fármacos , Dentina/efeitos dos fármacos , Silicatos/farmacologia , Células-Tronco/efeitos dos fármacos , Materiais Biocompatíveis , Proliferação de Células/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Polpa Dentária/citologia , Polpa Dentária/metabolismo , Matriz Extracelular/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Microscopia Eletrônica de Varredura , Modelos Biológicos , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Células-Tronco/citologia , Células-Tronco/metabolismo
19.
Dent Mater ; 33(6): 743-751, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28465067

RESUMO

OBJECTIVES: Assessing the role of dentinal fluid proteins in trans-dentinal diffusion of free monomers in vitro. METHODS: An artificial pulp chamber (APC) topped human dentin disks was used. A simplified two-step etch-and-rinse adhesive was formulated with 2-hydroethyl-methacrylate (HEMA), Bisphenol-A-diglycidyl-methacrylate (BisGMA), using Camphorquinone/tertiary amine as initiators. Two extraction media were used: buffered saline (Control), buffered saline with 1% bovine serum albumin (BSA). Samples were acid-etched, rinsed, air dried. Simplified primer was used, adhesive applied then light cured with a LED curing. Monomer diffusion was assessed by reverse phase HPLC. RESULTS: Quantifiable amounts of HEMA were detected in both extraction media while BisGMA was present in quantifiable amounts in BSA medium only. Diffused monomers concentrations were significantly higher for both monomers in BSA extraction medium. SIGNIFICANCE: Albumin is sometimes referred to as taxi protein for its ability to bind and transport hydrophobic ligands. From our results, we hypothesized that albumin can also transport unbound monomers released from dental adhesive through the dentin barrier. However, dentinal fluid proteins like albumin could have significant effect on monomer diffusion through dentin to the dental pulp transporting highly hydrophobic molecules like BisGMA and enhancing diffusion of more hydrophilic ones like HEMA. These results demonstrate a new possible mechanism for cytotoxicity of resin monomers.


Assuntos
Albuminas/fisiologia , Bis-Fenol A-Glicidil Metacrilato , Cimentos Dentários , Adesivos Dentinários/farmacocinética , Dentina/metabolismo , Cimentos de Resina/farmacocinética , Condicionamento Ácido do Dente , Colagem Dentária , Humanos , Metacrilatos
20.
PLoS One ; 11(5): e0155450, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27196425

RESUMO

OBJECTIVES: The development of CAD-CAM techniques called for new materials suited to this technique and offering a safe and sustainable clinical implementation. The infiltration of resin in a ceramic network under high pressure and high temperature defines a new class of hybrid materials, namely polymer infiltrated ceramics network (PICN), for this purpose which requires to be evaluated biologically. We used oral stem cells (gingival and pulpal) as an in vitro experimental model. METHODS: Four biomaterials were grinded, immersed in a culture medium and deposed on stem cells from dental pulp (DPSC) and gingiva (GSC): Enamic (VITA®), Experimental Hybrid Material (EHM), EHM with initiator (EHMi) and polymerized Z100™ composite material (3M®). After 7 days of incubation; viability, apoptosis, proliferation, cytoskeleton, inflammatory response and morphology were evaluated in vitro. RESULTS: Proliferation was insignificantly delayed by all the tested materials. Significant cytotoxicity was observed in presence of resin based composites (MTT assay), however no detectable apoptosis and some dead cells were detected like in PICN materials. Cell morphology, major cytoskeleton and extracellular matrix components were not altered. An intimate contact appeared between the materials and cells. CLINICAL SIGNIFICANCE: The three new tested biomaterials did not exhibit adverse effects on oral stem cells in our experimental conditions and may be an interesting alternative to ceramics or composite based CAD-CAM blocks.


Assuntos
Materiais Biocompatíveis/química , Polpa Dentária/metabolismo , Gengiva/metabolismo , Polímeros/química , Resinas Sintéticas/química , Células-Tronco/citologia , Adipócitos/citologia , Apoptose , Diferenciação Celular , Proliferação de Células , Separação Celular , Sobrevivência Celular , Cerâmica , Meios de Cultura , Citometria de Fluxo , Temperatura Alta , Humanos , Inflamação , Microscopia Eletrônica de Varredura , Osteogênese , Fenolsulfonaftaleína/química , Pressão
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