RESUMO
Treatment for dental avulsion cases is early or late replantation of the traumatized teeth. Prognosis of the replanted tooth depends on the level of periodontal injury. Adipose tissue stem cells (ATSCs) were reported to improve periodontal ligament tissue (PDL) regeneration. Fibrin sealant (FS) contains thrombin and fibrinogen to form an adhesive fibrin clot routinely used in surgical procedures. Here, we aimed to investigate the effects of ATSCs + FS treatment on healing of PDL after tooth replantation in a rat model. After 60 min of extraction, maxillary central incisor teeth were replanted with ATSCs + FS. Two months later, the rats were sacrificed and hemimaxilla blocks were dissected out for histological analysis. The results showed that there was a significant improvement in histological findings of ATSCs + FS treated group compared to only FS treated and non-treated groups corresponding to reduced inflammatory resorption and increased new PDL formation. Furthermore, the ankylosis levels were lowered after ATSCs + FS treatment. Singular use of FS improved PDL healing moderately. Our results indicated that ATSCs + FS treatment improves PDL healing after tooth replantation suggesting a new therapeutic potential in the treatment of dental avulsion cases.
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OBJECTIVE: To transplant bone marrow-derived mesenchymal stem cells (MSCs) into the interpremaxillary suture after rapid maxillary expansion with the aim of increasing new bone formation in the suture. MATERIALS AND METHODS: Nineteen male Wistar rats were divided into two groups (control, n â=â 9; experimental, n â=â 10). Both groups were subjected to expansion for 5 days, and 50 cN of force was applied to the maxillary incisors with a helical spring. Pkh67(+) (green fluorescent dye)-labeled MSCs were applied to the interpremaxillary suture after force application into the interpremaxillary suture of rats. Bone formation in the sutural area was histomorphometrically evaluated, including the amount of new bone formation (µm(2)), number of osteoblasts, number of osteoclasts, and number of vessels. Mann-Whitney U-test was used for statistical evaluation at the P < .05 level. RESULTS: After 10 days of retention, Pkh67(+) can be detected in suture mostly in the injection site under fluorescence microscope. Histomorphometric analysis revealed that a single local injection of MSCs into the midpalatal suture increased the new bone formation in the suture by increasing the number of osteoblasts and new vessel formation, compared with controls injected with phosphate-buffered saline. CONCLUSIONS: This preclinical study might provide foundations for the underlying potential clinical use of MSCs after maxillary expansion. Given the fact that MSCs are currently in use in clinical trials, this approach might be a feasible treatment strategy to accelerate new bone tissue formation in midpalatal suture and to shorten the treatment period for patients undergoing maxillary expansion reinforcement.
Assuntos
Maxila/anatomia & histologia , Transplante de Células-Tronco Mesenquimais/métodos , Osteogênese/fisiologia , Técnica de Expansão Palatina , Animais , Contagem de Células , Técnicas de Cultura de Células , Suturas Cranianas/anatomia & histologia , Suturas Cranianas/irrigação sanguínea , Corantes Fluorescentes , Masculino , Maxila/irrigação sanguínea , Microscopia de Fluorescência , Neovascularização Fisiológica/fisiologia , Compostos Orgânicos , Desenho de Aparelho Ortodôntico , Fios Ortodônticos , Osteoblastos/citologia , Osteoclastos/citologia , Técnica de Expansão Palatina/instrumentação , Ratos , Ratos WistarRESUMO
Bone morphogenetic proteins (BMPs) initiate, promote, and maintain odontogenesis and osteogenesis. In this study, we studied the effect of bone morphogenic protein 2 (BMP 2) and bone morphogenic protein 7 (BMP 7) as differentiation inducers in tooth and bone regeneration. We compared the effect of BMP 2 and BMP 7 on odontogenic and osteogenic differentiation of human tooth germ stem cells (hTGSCs). Third molar-derived hTGSCs were characterized with mesenchymal stem cell surface markers by flow cytometry. BMP 2 and BMP 7 were transfected into hTGSCs and the cells were seeded onto six-well plates. One day after the transfection, hTGSCs were treated with odontogenic and osteogenic mediums for 14 days. For confirmation of odontogenic and osteogenic differentiation, mRNA levels of BMP2, BMP 7, collagen type 1 (COL1A), osteocalsin (OCN), and dentin sialophosphoprotein (DSPP) genes were measured by quantitative real-time PCR. In addition to this, immunocytochemistry was performed by odontogenic and osteogenic antibodies and mineralization obtained by von Kossa staining. Our results showed that the BMP 2 and BMP 7 both promoted odontogenic and osteogenic differentiation of hTGSCs. Data indicated that BMP 2 treatment and BMP 7 treatment induce odontogenic differentiation without affecting each other, whereas they induce osteogenic differentiation by triggering expression of each other. These findings provide a feasible tool for tooth and bone tissue engineering.
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Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 7/genética , Odontogênese/genética , Osteogênese/genética , Células-Tronco/metabolismo , Germe de Dente/metabolismo , Adolescente , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 7/metabolismo , Calcificação Fisiológica , Diferenciação Celular , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Dente Molar/citologia , Dente Molar/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sialoglicoproteínas/genética , Sialoglicoproteínas/metabolismo , Células-Tronco/citologia , Germe de Dente/citologia , TransfecçãoRESUMO
OBJECTIVE: The aim of this study was to compare the cytotoxic effects of endodontic cements on human tooth germ stem cells (hTGSCs). MTA Fillapex, a mineral trioxide aggregate (MTA)-based, salicylate resin containing root canal sealer, was compared with iRoot SP, a bioceramic sealer, and AH Plus Jet, an epoxy resin-based root canal sealer. MATERIAL AND METHODS: To evaluate cytotoxicity, all materials were packed into Teflon rings (4 mmµ3 mm) and co-cultured with hTGSCs with the aid of 24-well Transwell permeable supports, which had a pore size of 0.4 µm. Coverslips were coated with MTA Fillapex, iRoot SP and AH Plus Jet and each coverslip was placed onto the bottom of one well of a six-well plate for scanning electron microscopy (SEM) analysis. Before the cytotoxicity and SEM analysis, all samples were stored at 37ºC and at 95% humidity and 5% CO2 for 24 hours to set. The cellular viability was analyzed using MTS test (3-(4,5-dimethyl-thiazol-2-yl)-5-(3-carboxy-methoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium). The cytotoxic effects and SEM visualization of the tested materials were analyzed at 24-hour, 72-hour, one-week and two-week periods. RESULTS: On the 1st day, only MTA Fillapex caused cytotoxicity compared to negative control (NC) group (p<0.008). No significant difference was observed between the other tested materials at this period (p>0.05). After 14 days of incubation with the test materials, MTA Fillapex exhibited significantly higher cytotoxicity compared with iRoot SP, AH Plus Jet and the NC group (P<0.008). In the SEM analysis, the highest levels of cell attachment were observed for iRoot SP and the control group. After 24 hours, MTA Fillapex reduced the number of cells attached to the surface. CONCLUSIONS: Within the limitations of this study, sealers exerted different cytotoxic effects on hTGSCs. Although all materials have exerted cellular toxicity, iRoot SP and AH Plus Jet may promote better attachment to hTGSCs.
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Compostos de Cálcio/toxicidade , Cimentos Dentários/toxicidade , Silicatos/toxicidade , Células-Tronco/efeitos dos fármacos , Germe de Dente/citologia , Compostos de Alumínio/toxicidade , Materiais Biocompatíveis/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Combinação de Medicamentos , Resinas Epóxi/toxicidade , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Óxidos/toxicidade , Materiais Restauradores do Canal Radicular/toxicidade , Estatísticas não Paramétricas , Propriedades de Superfície/efeitos dos fármacos , Fatores de TempoRESUMO
The use of stem-cell-based therapies in regenerative medicine and in the treatment of disorders such as Parkinson, Alzheimer's disease, diabetes, spinal cord injuries, and cancer has been shown to be promising. Among all stem cells, mesenchymal stem cells (MSCs) were reported to have anti-apoptotic, immunomodulatory, and angiogenic effects which are attributed to the restorative capacity of these cells. Human tooth germ stem cells (HTGSCs) having mesenchymal stem cell characteristics have been proven to exert high proliferation and differentiation capacity. Unlike bone-marrow-derived MSCs, HTGSCs can be easily isolated, expanded, and cryopreserved, which makes them an alternative stem cell source. Regardless of their sources, the stem cells are exposed to physical and chemical stresses during cryopreservation, hindering their therapeutic capacity. Amelioration of the side effects of cryopreservation on MSCs seems to be a priority in order to maximize the therapeutic efficacy of these cells. In this study, we tested the effect of Pluronic 188 (F68) on HTGSCs during long-term cryopreservation and repeated freezing and defrosting cycles. Our data revealed that F68 has a protective role on survival and differentiation of HTGSCs in long-term cryopreservation.
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Criopreservação/métodos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Poloxâmero/farmacologia , Germe de Dente/citologia , Adolescente , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ácidos Graxos/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismoRESUMO
INTRODUCTION: The major challenge in dental pulp engineering is to make a successful combination of stem cells and biomaterials with the aim of providing the differentiation of stem cells into odontogenic cell types. Among biomaterials, some types of pluronics have been reported to increase bone formation of stem cells. The effect of these pluronics on odontogenic differentiation has not been addressed yet. This study aimed to examine the effect of pluronics F68, F127, and P85 on odontogenic differentiation of stem cells derived from third molar tooth germs of young adults. METHODS: Human tooth germ stem cells (hTGSCs) were induced to differentiate into odontogenic cells in the presence of different concentrations of pluronics. Differentiation efficiency was assessed by quantitative real-time polymerase chain reaction for determining expression messenger RNA levels and by immunocytostaining for determining the protein expression of odontogenic markers (ie, dentin sialoprotein, dentin matrix protein 1, bone morphogenic protein 2, bone morphogenic protein 7) by measuring alkaline phosphatase enzyme activity and lastly by von Kossa staining for determining mineralization. RESULTS: The results revealed for the first time that F68 has a great potential to boost odontogenic differentiation of hTGSCs. P85 was found to reduce cell viability during differentiation. F127 was nontoxic to hTGSCs but did not have any effect on differentiation. CONCLUSIONS: The positive effect of F68 on odontogenic differentiation might enable more efficient pulp regeneration. Yet, the exact mechanism of how F68 alters the differentiation pattern of hTGSCs remains to be investigated in the future studies.
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Odontogênese/efeitos dos fármacos , Poloxaleno/farmacologia , Poloxâmero/farmacologia , Células-Tronco/efeitos dos fármacos , Germe de Dente/citologia , Adolescente , Fosfatase Alcalina/análise , Fosfatase Alcalina/efeitos dos fármacos , Proteína Morfogenética Óssea 2/análise , Proteína Morfogenética Óssea 2/efeitos dos fármacos , Proteína Morfogenética Óssea 7/análise , Proteína Morfogenética Óssea 7/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Técnicas de Cultura de Células , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/análise , Colágeno Tipo I/efeitos dos fármacos , Cadeia alfa 1 do Colágeno Tipo I , Proteínas da Matriz Extracelular/análise , Proteínas da Matriz Extracelular/efeitos dos fármacos , Humanos , Dente Serotino/citologia , Fosfoproteínas/análise , Fosfoproteínas/efeitos dos fármacos , Sialoglicoproteínas/análise , Sialoglicoproteínas/efeitos dos fármacosRESUMO
OBJECTIVE: The aim of this study was to compare the cytotoxic effects of endodontic cements on human tooth germ stem cells (hTGSCs). MTA Fillapex, a mineral trioxide aggregate (MTA)-based, salicylate resin containing root canal sealer, was compared with iRoot SP, a bioceramic sealer, and AH Plus Jet, an epoxy resin-based root canal sealer. MATERIAL AND METHODS: To evaluate cytotoxicity, all materials were packed into Teflon rings (4 mmµ3 mm) and co-cultured with hTGSCs with the aid of 24-well Transwell permeable supports, which had a pore size of 0.4 µm. Coverslips were coated with MTA Fillapex, iRoot SP and AH Plus Jet and each coverslip was placed onto the bottom of one well of a six-well plate for scanning electron microscopy (SEM) analysis. Before the cytotoxicity and SEM analysis, all samples were stored at 37ºC and at 95% humidity and 5% CO2 for 24 hours to set. The cellular viability was analyzed using MTS test (3-(4,5-dimethyl-thiazol-2-yl)-5-(3-carboxy-methoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium). The cytotoxic effects and SEM visualization of the tested materials were analyzed at 24-hour, 72-hour, one-week and two-week periods. RESULTS: On the 1st day, only MTA Fillapex caused cytotoxicity compared to negative control (NC) group (p<0.008). No significant difference was observed between the other tested materials at this period (p>0.05). After 14 days of incubation with the test materials, MTA Fillapex exhibited significantly higher cytotoxicity compared with iRoot SP, AH Plus Jet and the NC group (P<0.008). In the SEM analysis, the highest levels of cell attachment were observed for iRoot SP and the control group. After 24 hours, MTA Fillapex reduced the number of cells attached to the surface. CONCLUSIONS: Within the limitations of this study, sealers exerted different cytotoxic effects on hTGSCs. Although all materials ...
Assuntos
Humanos , Compostos de Cálcio/toxicidade , Cimentos Dentários/toxicidade , Silicatos/toxicidade , Células-Tronco/efeitos dos fármacos , Germe de Dente/citologia , Compostos de Alumínio/toxicidade , Materiais Biocompatíveis/toxicidade , Células Cultivadas , Sobrevivência Celular/efeitos dos fármacos , Combinação de Medicamentos , Resinas Epóxi/toxicidade , Teste de Materiais , Microscopia Eletrônica de Varredura , Óxidos/toxicidade , Materiais Restauradores do Canal Radicular/toxicidade , Estatísticas não Paramétricas , Propriedades de Superfície/efeitos dos fármacos , Fatores de TempoRESUMO
Bone-marrow-derived mesenchymal stem cells (MSCs) demonstrate neuro-protective effects in several disease models. By producing growth-factors, cytokines and chemokines, they promote survival of neurons in damaged brain areas. Alternative MSC sources, such as human tooth germ stem cells (hTGSCs), have been investigated for their neuro-protective properties. They ameliorate effects of neuro-toxic agents by paracrine mechanisms, however these secreted bio-active molecules are not yet characterized. Therefore, the current study aimed to provide a detailed analysis of the secretome of hTGSCs. Brain cells were exposed to various toxic materials, including Alzheimer's ß-amyloid peptide (ß-AP) and 6-hydroxy-dopamine (6-OHDA). When co-cultured with hTGSCs, the activity of a number of anti-oxidant enzymes (catalase, glutathione-s-transferase, glutathione-peroxidase, superoxide-dismutase) was increased and neuronal death/apoptosis was subsequently reduced. The composition of the secreted bio-active materials is influenced by various pre-existing factors such as oxygen and glucose deprivation and the age of cells (passage number). This report reveals for the first time that the neuro-protective secretome of hTGSCs and the micro-environment of cells have a mutual and dynamic impact on one another.
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Meio Ambiente , Células-Tronco/fisiologia , Germe de Dente/fisiologia , Adolescente , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Proteínas Reguladoras de Apoptose/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Quimiocinas/metabolismo , Criança , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Dente Serotino/fisiologia , Neovascularização Fisiológica/fisiologia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/patologia , Fármacos Neuroprotetores/metabolismo , Neurotoxinas/antagonistas & inibidores , Neurotoxinas/toxicidade , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Reação em Cadeia da Polimerase em Tempo Real , Células-Tronco/metabolismo , Germe de Dente/metabolismoRESUMO
INTRODUCTION: Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder characterized by immune dysregulation because of a mutation in cathepsin c gene, resulting in hyperkeratosis of the palms, soles, elbows, and knees combined with premature loss of the primary and permanent dentitions. Periodontal tissue abnormalities in PLS patients were reported previously. However, less is known about dental pulp tissue derived cells of PLS patients. This study aimed to show stem cell potential of PLS dental pulp stem cells (DPSCs) and provide new evidence regarding the pathophysiology of the disease. METHODS: DPSCs were characterized by using flow cytometry and immunocytochemistry. They were also induced to differentiate into adipogenic, osteogenic, chondrogenic, odontogenic, and myogenic cells. RESULTS: The results revealed that PLS DPSCs are stained positive for mesenchymal stem cells surface markers CD29, CD73, CD90, CD105, and CD166. PLS DPSCs were able to differentiate into adipogenic, osteogenic, chondrogenic, and odontogenic cell types properly. PLS DPSCs expressed embryonic stem cell markers Oct4, Sox2, cMYc, and Klf4 and showed similar proliferation rate compared with DPSCs isolated from healthy young controls. Interestingly, it was found that unlike the healthy DPSCs, PLS DPSCs are not able to form myotubes with correct morphology. CONCLUSIONS: These data are being reported for the first time; therefore, they might provide new insights to the pathology of the disease. Our results suggest that the PLS DPSCs might be an autologous stem cell source for PLS patients for cellular therapy of alveolar bone defects and other dental tissue abnormalities observed in PLS.
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Polpa Dentária/citologia , Células-Tronco Mesenquimais/citologia , Doença de Papillon-Lefevre/patologia , 5'-Nucleotidase/análise , Adipogenia/fisiologia , Antígenos CD/análise , Adesão Celular/fisiologia , Moléculas de Adesão Celular Neuronais/análise , Diferenciação Celular/fisiologia , Proliferação de Células , Separação Celular/métodos , Condrogênese/fisiologia , Endoglina , Proteínas Fetais/análise , Citometria de Fluxo/métodos , Proteínas Ligadas por GPI/análise , Humanos , Imuno-Histoquímica , Integrina beta1/análise , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/análise , Células-Tronco Mesenquimais/classificação , Desenvolvimento Muscular/fisiologia , Fibras Musculares Esqueléticas/patologia , Fator 3 de Transcrição de Octâmero/análise , Odontogênese/fisiologia , Osteogênese/fisiologia , Proteínas Proto-Oncogênicas c-myc/análise , Receptores de Superfície Celular/análise , Fatores de Transcrição SOXB1/análise , Antígenos Thy-1/análise , Dedos de ZincoRESUMO
Alzheimer's dementia (AD) is a degenerative brain disorder characterized mainly by cholinergic failure, but other neuro-transmitters are also deficient especially at late stages of the disease. Misfolded ß-amyloid peptide has been identified as a causative agent, however inflammatory changes also play a pivotal role. Even though the most prominent pathology is seen in the cognitive functions, specific abnormalities of the central nervous system (CNS) are also reflected in the periphery, particularly in the immune responses of the body. The aim of this study was to characterize the dopaminergic and serotonergic systems in AD, which are also markedly disrupted along with the hallmark acetyl-choline dysfunction. Peripheral blood mono-nuclear cells (PBMCs) from demented patients were judged against comparison groups including individuals with late-onset depression (LOD), as well as non-demented and non-depressed subjects. Cellular sub-populations were evaluated by mono-clonal antibodies against various cell surface receptors: CD4/CD8 (T-lymphocytes), CD19 (B-lymphocytes), CD14 (monocytes), and CD56 (natural-killer (NK)-cells). The expressions of dopamine D(3) and D(4), as well as serotonin 5-HT(1A), 5-HT(2A), 5-HT(2B) and 5-HT(2C) were also assessed. There were no significant differences among the study groups with respect to the frequency of the cellular sub-types, however a unique profound increase in 5-HT(2C) receptor exclusively in NK-cells was observed in AD. The disease-specific expression of 5-HT(2C), as well as the NK-cell cyto-toxicity, has been linked with cognitive derangement in dementia. These changes not only corroborate the existence of bi-directional communication between the immune system and the CNS, but also elucidate the role of inflammatory activity in AD pathology, and may serve as potential biomarkers for less invasive and early diagnostic purposes as well.
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Doença de Alzheimer/metabolismo , Células Matadoras Naturais/metabolismo , Receptor 5-HT2C de Serotonina/biossíntese , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Depressão/metabolismo , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Receptores de Dopamina D3/biossíntese , Receptores de Dopamina D4/biossíntese , Receptores de Serotonina/biossínteseRESUMO
OBJECT: Chordomas are locally aggressive bone tumors known to arise from the remnants of the notochord. Because chordomas are rare, molecular studies aimed at developing new therapies are scarce and new approaches are needed. Chordoma cells and cancer stem-like cells share similar characteristics, including self-renewal, differentiation, and resistance to chemotherapy. Therefore, it seems possible that chordomas might contain a subpopulation of cancer stem-like cells. The aim of this study is to determine whether cancer stem-like cells might be present in chordomas. METHODS: In this study, the authors used gene expression analysis for common cancer stem-like cellmarkers, including c-myc, SSEA-1, oct4, klf4, sox2, nanog, and brachyury, and compared chordoma cells and tissues with nucleus pulposus tissues (disc degenerated nontumorigenic tissues). Differentiation through agents such as all-trans retinoic acid and osteogenic differentiation medium was induced to the chordoma cells. Additionally, U-CH1 cells were sorted via magnetic cell sorting for stem cell markers CD133 and CD15. After separation, positive and negative cells for these markers were grown in a nonadherent environment, soft agar, to determine whether the presence of these cancer stem-like cells might be responsible for initiating chordoma. The results were compared with those of untreated cells in terms of migration, proliferation, and gene expression by using reverse transcriptase polymerase chain reaction. RESULTS: The results indicate that chordoma cells might be differentiating and committing into an osteogenic lineage when induced with the osteogenic differentiation agent. Chordoma cells that are induced with retinoic acid showed slower migration and proliferation rates when compared with the untreated cells. Chordoma cells that were found to be enriched by cancer stem-like cell markers, namely CD133 and CD15, were able to live in a nonadherent soft agar medium, demonstrating a self-renewal capability. To the authors' knowledge, this is the first time that cancer stem-like cell markers were also found to be expressed in chordoma cells and tissues. CONCLUSIONS: Cancer stem-like cell detection might be an important step in determining the recurrent and metastatic characteristics of chordoma. This finding may lead to the development of new approaches toward treatments of chordomas.
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Cordoma/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias da Medula Espinal/patologia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Sobrevivência Celular/genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Criança , Cordoma/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Fator 4 Semelhante a Kruppel , Masculino , Pessoa de Meia-Idade , Neoplasias da Medula Espinal/genética , Adulto JovemRESUMO
BACKGROUND: Boric acid is widely used in biology, but its body weight reducing effect is not researched. METHODS: Twenty mice were divided into two equal groups. Control group mice drank standard tap water, but study group mice drank 0.28mg/250ml boric acid added tap water over five days. Total body weight changes, major organ histopathology, blood biochemistry, urine and feces analyses were compared. RESULTS: Study group mice lost body weight mean 28.1% but in control group no weight loss and also weight gained mean 0.09% (p<0.001). Total drinking water and urine outputs were not statistically different. Cholesterol, LDL, AST, ALT, LDH, amylase and urobilinogen levels were statistically significantly high in the study group. Other variables were not statistically different. No histopathologic differences were detected in evaluations of all resected major organs. CONCLUSION: Low dose oral boric acid intake cause serious body weight reduction. Blood and urine analyses support high glucose, lipid and middle protein catabolisms, but the mechanism is unclear.
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Ácidos Bóricos/farmacologia , Redução de Peso/efeitos dos fármacos , Administração Oral , Animais , Ácidos Bóricos/administração & dosagem , CamundongosRESUMO
OBJECT: Chordoma is a rare type of malignant bone tumor and is known to arise from the remnants of the notochord. Resistance to chemotherapy makes the treatment of chordoma difficult; therefore, new approaches need to be developed to cure this disease. Differentiation therapy, using various differentiating agents, is attracting oncologists as a common therapeutic method to treat other tumors. Based on forcing cells to mature into other lineages, differentiation therapy might be an available method to treat chordomas in addition to conventional therapies. METHODS: In this study a chordoma cell line, U-CH1, was exposed to several chemotherapeutic agents including vincristine, doxorubicin, cisplatin, etoposide, fludarabine, methotrexate, nilotinib, and imatinib mesylate under appropriate conditions. The first group of U-CH1 cells was exposed to drugs only and the second group of cells was exposed to the simultaneous treatment of 1 µM all-trans retinoic acid (ATRA) and chemotherapeutic agents in differentiation therapy. The efficacy of the differentiation method was assessed by measuring the viability of U-CH1 cells. RESULTS: Vincristine, doxorubicin, etoposide, cisplatin, and fludarabine, each at a concentration of 10 µM, decreased the number of chordoma cells when given alone down to 11%, 0%, 30%, 67%, and 3%, respectively. Etoposide and cisplatin, each at a concentration of 10 µM, reduced the percentage of viable chordoma cells in a more effective way when given with 1 µM ATRA simultaneously, reducing the number of viable cells to 14% and 9%, respectively. On the other hand, imatinib and nilotinib, each at a concentration of 3 µM, as well as 10 µM methotrexate, showed no decrease in the number of cancer cells. CONCLUSIONS: The results suggest that chordoma cells may be treated using the differentiation method in a more effective way than when they are treated with chemotherapeutic agents alone. This new approach may be an alternative method to conventional therapies in the treatment of chordoma.
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Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Cordoma/tratamento farmacológico , Cordoma/patologia , Antibióticos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Benzamidas , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Linhagem da Célula/efeitos dos fármacos , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Etoposídeo/farmacologia , Humanos , Mesilato de Imatinib , Metotrexato/farmacologia , Piperazinas/farmacologia , Pirimidinas/farmacologia , Vidarabina/análogos & derivados , Vidarabina/farmacologia , Vincristina/farmacologiaRESUMO
INTRODUCTION: Biocompatibility of pulp capping materials is important for successful use in dentistry. These materials should be nontoxic and permissive for proliferation and induction of odontogenic differentiation of pulp cells. The aim of our study was to evaluate the effects of enamel matrix derivative (EMD), mineral trioxide aggregate (MTA), and calcium hydroxide-containing cement (DYCAL) on proliferation and odontogenic differentiation of human tooth germ stem cells (hTGSCs) in which cells belonging to both pulp tissue and dental follicle exist. METHODS: The 96-well plates, 24-well plates, and special chamber slides were coated with biomaterials for cell proliferation, differentiation, and scanning electron microscopy analysis. Odontogenic differentiation of hTGSCs was evaluated by analyzing mRNA expression of dentin sialophosphoprotein (DSPP) by real-time polymerase chain reaction expression analysis, measurement of alkaline phosphatase activity, and visualization of calcium depositions by von Kossa staining. RESULTS: Our results demonstrate that EMD is the best material in terms of inducing differentiation and proliferation of hTGSCs. DYCAL was found to be toxic to hTGSCs; however, EMD-coated DYCAL showed less toxicity. EMD-coated MTA was not efficient at inducing proliferation and differentiation. CONCLUSIONS: Pulp capping materials come in direct contact with dental pulp cells; thus, they require comprehensive evaluation of interactions between cells and biomaterials. Therefore, we cultured hTGSCs, capable of odontogenic differentiation, on pulp capping materials directly. Our results suggest that combination of capping materials with EMD would increase the quality of capping by increasing biocompatibility of capping materials.
Assuntos
Compostos de Alumínio/farmacologia , Materiais Biocompatíveis/farmacologia , Compostos de Cálcio/farmacologia , Hidróxido de Cálcio/farmacologia , Cimentos Dentários/farmacologia , Proteínas do Esmalte Dentário/farmacologia , Óxidos/farmacologia , Agentes de Capeamento da Polpa Dentária e Pulpectomia/farmacologia , Silicatos/farmacologia , Células-Tronco/efeitos dos fármacos , Germe de Dente/efeitos dos fármacos , Adolescente , Fosfatase Alcalina/análise , Biomarcadores/análise , Calcificação Fisiológica/efeitos dos fármacos , Cálcio/análise , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/análise , Polpa Dentária/citologia , Saco Dentário/citologia , Combinação de Medicamentos , Proteínas da Matriz Extracelular/análise , Imunofluorescência , Humanos , Microscopia Eletrônica de Varredura , Minerais/farmacologia , Osteogênese/efeitos dos fármacos , Fosfoproteínas/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sialoglicoproteínas/análise , Germe de Dente/citologiaRESUMO
Aflatoxins (Aspergillus flavus toxins) are one of the natural toxic molecules which are produced by a group of fungi called Aspergillus. Foods and drinks contaminated with aflatoxins cause global health and environmental problems. Today in many developing countries, these toxins are leading cause of some liver cancers and serious gastrointestinal problems. Aflatoxins, which are well known to be mutagenic, carcinogenic, hepatotoxic, and immunosuppressive, exert inhibitory effects on biological processes including DNA synthesis, DNA-dependent RNA synthesis, DNA repair, and protein synthesis. Aflatoxins B(1) (AFB(1)) is the most widespread oxidative agent of the aflatoxins. Numerous diverse compounds and extracts have been reported to reduce the aflatoxins induced oxidative stress in the body. Most of these inhibitors including phenylpropanoids, terpenoids, alkaloids, and vitamins are originally derived from plants. Among these, being essential biomolecules, vitamins are used as coenzymes in very significant biological reactions. They also function as nonenzymatic antioxidative agents protecting the cells from oxidative stress-induced toxicity and transformation. This chapter reviews the mechanism of AFB(1)-induced oxidative stress and focuses on the protective effects of vitamins A, C, and E on reducing this stress.