Exosomes derived from mesenchymal stem cells (MSCs) have demonstrated regenerative potential for cell-free bone tissue engineering, nevertheless, certain challenges, including the confined ...therapeutic potency of exosomes and ineffective delivery method, are still persisted. Here, we confirmed that hypoxic precondition could induce enhanced secretion of exosomes from stem cells from human exfoliated deciduous teeth (SHEDs) via comprehensive proteomics analysis, and the corresponding hypoxic exosomes (H-Exo) exhibited superior potential in promoting cellular angiogenesis and osteogenesis via the significant up-regulation in focal adhesion, VEGF signaling pathway, and thyroid hormone synthesis. Then, we developed a platform technology enabling the effective delivery of hypoxic exosomes with sustained release kinetics to irregular-shaped bone defects via injection. This platform is based on a simple adsorbing technique, where exosomes are adsorbed onto the surface of injectable porous poly(lactide-co-glycolide) (PLGA) microspheres with bioinspired polydopamine (PDA) coating (PMS-PDA microspheres). The PMS-PDA microspheres could effectively adsorb exosomes, show sustained release of H-Exo for 21 days with high bioactivity, and induce vascularized bone regeneration in 5-mm rat calvarial defect. These findings indicate that the hypoxic precondition and PMS-PDA porous microsphere-based exosome delivery are efficient in inducing tissue regeneration, hence facilitating the clinical translation of exosome-based therapy.
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•Hypoxic precondition regulates the transcriptomics of SHEDs derived exosomes.•H-Exo exhibits enhanced angiogenesis and osteogenesis capacity.•PMS-PDA microspheres can effectively adsorb exosomes, and show sustained release of exosomes for 21 days.•PMS-PDA + H-Exo promotes vascularized bone regeneration in 5-mm rat calvarial defects.
OBJECTIVEIn this study, we aimed to investigate the effects of varying glucose concentrations on the proliferation and senescence of stem cells from human exfoliated deciduous teeth (SHED) compared ...to human bone marrow-derived mesenchymal stem cells (hBMSC), and preliminarily clarify the difference of glucose metabolism between SHED and hBMSC.DESIGNWe cultured SHED and hBMSC in the presence of increasing glucose concentrations to study the role of glucose in cell viability, proliferation, and senescence. Gene expression related to the stemness of mesenchymal stem cells was evaluated using real-time quantitative reverse transcription-polymerase chain reaction. In addition, glucose consumption, lactic acid production, oxidative phosphorylation, and glycolysis were measured to analyze glucose metabolism and expression of autophagy-related markers, including microtubule-associated proteins 1 A/1B light chain 3 B and p62.RESULTSWhile a high glucose level (4.5 g/L) promoted the proliferation of both SHED and hBMSC, it delayed senescence in SHED via autophagy inhibition but accelerated hBMSC senescence. In contrast to that in hBMSC, glycolysis in SHED was enhanced under the high-glucose culture condition.CONCLUSIONSThe glycometabolism of SHED and hBMSC differed, and a high glucose culture medium was more favorable for SHED.
Background/Aim: The determination of remaining dentin thickness (RDT) is quite critical in providing appropriate treatment indications especially in deciduous molars. The aim of this study was to ...investigate the accuracy of in vitro pre-operative radiographs before caries removal in RDT measurement. Material and Methods: This in vitro study was conducted with 30 lower deciduous second molars with deep approximal dentinal caries. Following the standardized digital radiographs were obtained, RDT was measured by determining the closest distance between the carious lesion and the pulp chamber on the computer software. After caries removal, the samples were sectioned in mesio-distal direction and photographed. RDT was measured on photographs similarly to radiographic measurements. In statistical analysis, Interclass Correlation Coefficient (ICC), Wilcoxon-Signed and Bland Altman Plot (BAP) tests were performed to determine the agreement and statistically difference. Results: The mean RDT value in photographs was found to be 10% higher than measured on radiographs. Although, correlation coefficient was within confidence interval, both RDT values showed good but not excellent agreement (correlation coefficient= 0.812). Also, BAP test did not demonstrate strong agreement. In descriptive statistics, significant difference was found between two measurements (p<0.05). Conclusions: Pre-operative radiological examination can not alone provide reliable results regarding the accurate determination depth of caries lesions. Clinicians should also consider operative diagnostic criteria for appropriate treatment options in deciduous teeth.
Background and purpose: In this study we aimed to identify the association between birth weight and first primary tooth eruption. Materials and methods: This retrospective cohort study was done in ...infants attending for 12 and 18 months vaccination in Qaemshahr health centers. Multi-stage cluster sampling was performed. Information, including birth weight, height, and head circumference were extracted from vaccination cards. Other information including feeding type, gestational age, type of delivery, and the time of first primary tooth eruption was also obtained. Pearson statistical test and linear regression model were applied to identify the relationship between first tooth eruption and other variables. Results: Data of 704 children were analyzed. The mean values for body weight, height and head circumference at birth were 3222 ± 554 g, 50.01± 2.75 cm, and 35.20 ± 2.23 cm, respectively. Pearson test showed a significant reverse relationship between the time of first teeth eruption and birth weight (r= -0.091, P= 0.01), height (r= -0.122, P= 0.006), and head circumference (r = -0.147, P= 0.002). Linear regression analysis showed a significant revers relationship between head circumference and time of first teeth eruption (B= -0.11, P= 0.02). Conclusion: In current study, after adjustment of confounding variables, head circumference remaind reveresly associated with time of first teeth eruption. It seems that some variables such as gentic factors along with environmental factors affect ttime of first teeth eruption.
Deciduous teeth cavities represent a frequent type of illness, which constitutes one of the most important dental health problems in pre-school children, caused by the direct implications and the ...possible consequences that it may have on permanent teeth. Even if a decrease in the incidence of dental cavities is registered in the industrialized countries of the world, when it comes to deciduous teeth, the frequency of the cavities is still high, at least for some certain social groups of the population. The purpose of the study is to collect current data on dental morbidity in the preschool population. There is not as much data concerning dental health in pre-school children as there is about school children, the reason being that preschoolar children are more difficult to consult. Material and Method: The study was conducted in a pediatric-clinic in Bucharest for a period of 5 years (ian. 01, 2013-dec. 31, 2018). The children included in the study are children who have had tooth decay. The number of children who participated in the study is 276. Results and Discussions: Of the 276 children studied, the highest incidence of tooth decay was for the age group between 3-4 years. This may signify, on one hand, a relatively high number of cavities at a young age, and on the other hand, the level of parental interest in dental care. Conclusions: The main conclusion of our study highlights the need to establish dental health education programs in both national and community level, where kindergartens and schools, have a great potential for influencing dental health care habits in children.
Objectives
The aim was to assess the diagnostic ability of the crown‐to‐root length ratio of the primary second molar and the position of the corresponding underlying premolar in estimating future ...anchoring teeth exfoliation during maxillary expansion.
Setting and Sample Population
Fifty‐four subjects (30 females, 24 males; 108 teeth) aged 8.2 ± 1.0 years that underwent palatal expansion.
Methods
The upper second premolar position of the corresponding expander anchoring primary molar was determined in relation to the ipsilateral first permanent molar half‐pulp chamber (HPC) line on panoramic radiographs. Subjective and objective (based on measurements) assessments of the crown‐to‐root length ratio of anchoring primary molars were performed. Exfoliation after the expansion was recorded over a retention period of 12 months. All the assessments were performed individually by three examiners at two 3‐week‐apart sessions, trained and calibrated before enrolment. The intra‐/inter‐examiner agreements were evaluated, and the diagnostic accuracy of the methods was calculated.
Results
All methods exhibited almost perfect intra‐ and at least substantial inter‐examiner agreement (Kappa >0.8 and ≥0.63, respectively). Good diagnostic accuracy was seen for the premolar position to the HPC line (0.7‐0.8), while the crown‐to‐root length ratio methods exhibited hardly sufficient accuracy. The diagnostic agreement of the methods was fair.
Conclusions
When primary molars are considered as anchoring teeth for maxillary expansion, the premolar position in relation to the HPC line appears to be the most valid and reliable method for predicting their stability. Despite high repeatability values, the crown‐to‐root length ratio needs a cut‐off point re‐definition to increase its predicting ability.
Several studies have demonstrated that mesenchymal stem cells can ameliorate the inflammation of allergic rhinitis (AR) and correct the Th1/Th2 immune imbalance.
This study was performed to explore ...the immunomodulation properties of stem cells from human exfoliated deciduous teeth (SHEDs) in the treatment of AR in vivo and in vitro. BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection, and then SHEDs or bone marrow mesenchymal stem cells (BMMSCs) were injected intravenously before challenge. We evaluated nasal symptoms, inflammatory infiltration of nasal mucosa, immunoglobulin secretion, cytokine production, and mRNA expression in the spleen. In addition, peripheral blood mononuclear cells (PBMCs) from AR patients were cultured with SHEDs or BMMSCs in the presence of phytohemagglutinin (PHA). PBMCs cultured alone with or without PHA served as controls. After 3 days of culture, we examined the effect of SHEDs on T lymphocyte proliferation, cytokine secretion, and the proportion of Foxp3
Treg cells via flow cytometry. Finally, to determine the role of soluble factors (TGF-β
, PGE
) in the immunomodulatory mechanism, a cytokine neutralization assay was performed.
Nasal symptoms and inflammatory infiltration were significantly reduced after SHED administration. The OVA-specific IgE and IgG
levels in serum were significantly decreased, and the increased IL-4, IL-5, IL-13, and IL-17A levels in the spleen after OVA challenge were markedly downregulated, while the level of IFN-γ was upregulated by SHED administration. The mRNA expression levels also changed correspondingly. SHEDs significantly inhibited the proliferation of T lymphocytes; increased the levels of IFN-γ, IL-10, PGE
, and TGF-β
; decreased the levels of IL-4 and IL-17A; and induced the expansion of Treg cells in the coculture system. The neutralization of TGF-β
partly relieved the immunosuppression of SHEDs, but blocking PGE
did not. In addition, SHEDs were superior to BMMSCs in inhibiting the Th2 immune response in vivo and inducing the expansion of Treg cells in vitro.
These results suggest that SHEDs could correct the CD4
T cell immune imbalance via Treg cells and may be potential therapeutic agents for the treatment of allergic diseases, such as AR, in the future.
Mesenchymal stem cell transplantation (MSCT) regulates immune cells, and is a promising therapeutic approach for treating autoimmune diseases. Stem cells from human exfoliated deciduous teeth (SHED) ...are a unique postnatal stem cell population from the cranial neural crest with high self‐renewal, multipotent differentiation, and superior immunomodulatory properties. However, the mechanisms by which SHED can treat autoimmune diseases remain unclear. Sjögren's syndrome (SS) is an autoimmune disease histologically characterized by high lymphocytic infiltration in the salivary and lacrimal glands that results in dryness symptoms. This study explores the potential of systemic transplantation of SHED to ameliorate SS‐induced dryness symptoms in mice. Overall, SHED could rescue the balance of regulatory T cell (Treg)/T helper cell 17 (Th17) in the recipient SS mice. Mechanistically, SHED promoted Treg conversion and inhibited Th17 function via paracrine effects, which were related to the secretion of soluble programmed cell death ligand 1 (sPD‐L1). Moreover, it directly induced Th17 apoptosis via cell‐cell contact, leading to the up‐regulation of Treg and down‐regulation of Th17 cells. In summary, SHED‐mediated rescue of Treg/Th17 balance via the sPD‐L1/PD‐1 pathway ameliorates the gland inflammation and dryness symptoms in SS mice. These findings suggest that SHED are a promising stem cell source for the treatment of autoimmune diseases in the clinical setting.
Graphical
Stem cells from human exfoliated deciduous teeth (SHED)‐mediated rescue of Treg/Th17 balance via the sPD‐L1/PD‐1 pathway ameliorates the gland inflammation and dryness symptoms in SS mice, suggesting that SHED are a promising source for treating autoimmune diseases in a clinical setting.
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