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Frontiers in Cell and Developmental... 2024Mesenchymal stromal/stem cells (MSCs) are a heterogeneous population of multipotent cells that can be obtained from various tissues, such as dental pulp, adipose tissue,...
Proteomic analysis and functional validation reveal distinct therapeutic capabilities related to priming of mesenchymal stromal/stem cells with IFN-γ and hypoxia: potential implications for their clinical use.
Mesenchymal stromal/stem cells (MSCs) are a heterogeneous population of multipotent cells that can be obtained from various tissues, such as dental pulp, adipose tissue, bone marrow and placenta. MSCs have gained importance in the field of regenerative medicine because of their promising role in cell therapy and their regulatory abilities in tissue repair and regeneration. However, a better characterization of these cells and their products is necessary to further potentiate their clinical application. In this study, we used unbiased high-resolution mass spectrometry-based proteomic analysis to investigate the impact of distinct priming strategies, such as hypoxia and IFN-γ treatment, on the composition and therapeutic functionality of the secretome produced by MSCs derived from the amniotic membrane of the human placenta (hAMSCs). Our investigation revealed that both types of priming improved the therapeutic efficacy of hAMSCs, and these improvements were related to the secretion of functional factors present in the conditioned medium (CM) and exosomes (EXOs), which play crucial roles in mediating the paracrine effects of MSCs. In particular, hypoxia was able to induce a pro-angiogenic, innate immune response-activating, and tissue-regenerative hAMSC phenotype, as highlighted by the elevated production of regulatory factors such as VEGFA, PDGFRB, ANGPTL4, ENG, GRO-γ, IL8, and GRO-α. IFN-γ priming, instead, led to an immunosuppressive profile in hAMSCs, as indicated by increased levels of TGFB1, ANXA1, THBS1, HOMER2, GRN, TOLLIP and MCP-1. Functional assays validated the increased angiogenic properties of hypoxic hAMSCs and the enhanced immunosuppressive activity of IFN-γ-treated hAMSCs. This study extends beyond the direct priming effects on hAMSCs, demonstrating that hypoxia and IFN-γ can influence the functional characteristics of hAMSC-derived secretomes, which, in turn, orchestrate the production of functional factors by peripheral blood cells. This research provides valuable insights into the optimization of MSC-based therapies by systematically assessing and comparing the priming type-specific functional features of hAMSCs. These findings highlight new strategies for enhancing the therapeutic efficacy of MSCs, particularly in the context of multifactorial diseases, paving the way for the use of hAMSC-derived products in clinical practice.
PubMed: 38882056
DOI: 10.3389/fcell.2024.1385712 -
Scientific Reports Jun 2024For successful root canal treatment, adequate chemomechanical instrumentation to eliminate microorganisms and pulp tissue is crucial. This study aims to assess the...
For successful root canal treatment, adequate chemomechanical instrumentation to eliminate microorganisms and pulp tissue is crucial. This study aims to assess the organic tissue dissolving activity of various irrigation solutions on bovine tooth pulp tissue. 40 extracted bovine mandibular anterior teeth (n = 10) were used for the study. Bovine pulp pieces (25 ± 5 mg) were placed in 1.5 ml Eppendorf tubes. Each tooth pulp sample was then covered with 1.5 ml of different irrigation solutions, dividing them into four groups: Group 1 with freshly prepared 5% Boric acid, Group 2 with 5% NaOCl, Group 3 with Irritrol, and Group 4 with Saline. Samples were left at room temperature for 30 min, then dried and reweighed. The efficacy of tissue dissolution ranked from highest to lowest was found to be NaOCl, Boric Acid, Irritrol, and saline (p < 0.05). It was observed that the decrease in the NaOCl group was greater than the decrease in the Irritrol and saline groups, and the decrease in the Boric acid group was significantly greater than the decrease in the saline group (p < 0.05). It also emphasizes the need for future studies to further investigate the effects of Irritrol and Boric Acid on tissue dissolution.
Topics: Animals; Cattle; Boric Acids; Root Canal Irrigants; Dental Pulp; Sodium Hypochlorite; Therapeutic Irrigation
PubMed: 38879635
DOI: 10.1038/s41598-024-64904-w -
Pharmacological Research Jun 2024Cerebral ischemia-reperfusion injury (I/RI) is one of the principal pathogenic factors in the poor prognosis of ischemic stroke, for which current therapeutic options to...
Transfer of miR-877-3p via extracellular vesicles derived from dental pulp stem cells attenuates neuronal apoptosis and facilitates early neurological functional recovery after cerebral ischemia-reperfusion injury through the Bclaf1/p53 signaling pathway.
Cerebral ischemia-reperfusion injury (I/RI) is one of the principal pathogenic factors in the poor prognosis of ischemic stroke, for which current therapeutic options to enhance neurological recovery are notably insufficient. Dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) have promising prospects in stroke treatment and the specific underlying mechanisms have yet to be fully elucidated. The present study observed that DPSC-EVs ameliorated the degree of cerebral edema and infarct volume by reducing the apoptosis of neurons. Furthermore, the miRNA sequencing and functional enrichment analysis identified that miR-877-3p as a key component in DPSC-EVs, contributing to neuroprotection and anti-apoptotic effects. Following target prediction and dual-luciferase assay indicated that miR-877-3p interacted with Bcl-2-associated transcription factor (Bclaf1) to play a function. The miR-877-3p inhibitor or Bclaf1 overexpression reversed the neuroprotective effects of DPSC-EVs. The findings reveal a novel therapeutic pathway where miR-877-3p, transferred via DPSC-EVs, confers neuroprotection against cerebral I/RI, highlighting its potential in promoting neuronal survival and recovery post-ischemia.
PubMed: 38878918
DOI: 10.1016/j.phrs.2024.107266 -
Dental Materials : Official Publication... Jun 2024Quality control testing of dental materials requires a standard to enable the generation of reproducible and comparable data. Currently there are no standards for...
OBJECTIVES
Quality control testing of dental materials requires a standard to enable the generation of reproducible and comparable data. Currently there are no standards for testing materials used for vital pulp therapy. The aim of this study was to develop a new standard to evaluate solubility of pulp preservation materials.
METHODS
The solubility of three materials used for vital pulp therapy: Biodentine, TheraCal and Activa was evaluated using two international standards for dental materials ISO 4049:2019 (S1) and ISO 6876:2012 (S2). For both standards, a modified methodology was evaluated. This included changing the volume of the solution used (S1M, S2M), using Dulbecco's modified eagle medium (DMEM) as an alternative to water (S1D, S2D) and periodic solution change for the ISO 4049 method (S1P, S1MP). Materials were characterised before and after completion of solubility test using scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis.
RESULTS
The test materials exhibited different solubility values depending on the methodology used. Biodentine exhibited significantly lower solubility when lower volumes of solution were used when tested using both ISO methods (p ≤ 0.05). TheraCal and Activa showed negative solubility values after desiccation when tested using ISO 4049:2019. The Biodentine exhibited changes in its microstructure which was dependent on the method used to test solubility.
CONCLUSIONS
The solubility values obtained were dependent on the method used. It is thus important to use methods that replicate the clinical environment for meaningful evaluations.
PubMed: 38876829
DOI: 10.1016/j.dental.2024.05.028 -
Medicine Jun 2024To investigate the efficacy of 3 root canal sealants such as AH Plus, GuttaFlow and iRoot SP combined with warm gutta-percha vertical compression technique in the...
To investigate the efficacy of 3 root canal sealants such as AH Plus, GuttaFlow and iRoot SP combined with warm gutta-percha vertical compression technique in the treatment of dental pulp disease. This was a single-center retrospective study. 180 patients with dental pulp disease were divided into AH Plus group (n = 60), GuttaFlow group (n = 60) and iRoot SP group (n = 60) according to the different treatment methods. Patients in different groups were treated with corresponding root canal sealant combined with warm gutta-percha vertical compression technique. The quality of root canal filling, filling time, filling area ratio, the incidence of pain after operation, serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and efficacy at 6 months after operation were compared among the 3 groups, respectively. The filling time in the GuttaFlow group and the iRoot SP group was significantly shorter than that in the AH Plus group (P < .001). There were significant differences in pain grade (P = .015) and pain rate (P = .016) among the 3 groups, and the pain rate in the GuttaFlow group and the iRoot SP group was significantly lower than that in the AH Plus group (P = .016). The time-point effect, intergroup effect and time-groups effect of serum TNF-α and IL-6 were significantly different (P < .001), and the levels of the 3 groups after treatment were significantly lower than those before treatment (P < .05), and the levels were significantly lower in the GuttaFlow group and the iRoot SP group (P < .05). There were significant differences in efficacy grading and effective rate among the 3 groups (P = .028), and the effective rate of iRoot SP group was significantly higher than that of AH Plus group (P < .05). The iRoot SP or GuttaFlow as root canal sealant combined with warm gutta-percha vertical compression technique in the treatment of dental pulp disease is better than AH Plus, and the former one can shorten the filling time, relieve the postoperative pain and improve the inflammatory response, but the long-term apical sealing effect of iRoot SP is better than GuttaFlow.
Topics: Humans; Female; Male; Retrospective Studies; Adult; Root Canal Filling Materials; Gutta-Percha; Dental Pulp Diseases; Interleukin-6; Middle Aged; Tumor Necrosis Factor-alpha; Treatment Outcome; Young Adult; Drug Combinations; Dimethylpolysiloxanes
PubMed: 38875398
DOI: 10.1097/MD.0000000000038414 -
Regenerative Biomaterials 2024Pulp regeneration remains a crucial target in the preservation of natural dentition. Using decellularized extracellular matrix is an appropriate approach to mimic...
Pulp regeneration remains a crucial target in the preservation of natural dentition. Using decellularized extracellular matrix is an appropriate approach to mimic natural microenvironment and facilitate tissue regeneration. In this study, we attempted to obtain decellularized extracellular matrix from periapical lesion (PL-dECM) and evaluate its bioactive effects. The decellularization process yielded translucent and viscous PL-dECM, meeting the standard requirements for decellularization efficiency. Proteomic sequencing revealed that the PL-dECM retained essential extracellular matrix components and numerous bioactive factors. The PL-dECM conditioned medium could enhance the proliferation and migration ability of periapical lesion-derived stem cells (PLDSCs) in a dose-dependent manner. Culturing PLDSCs on PL-dECM slices improved odontogenic/angiogenic ability compared to the type I collagen group. , the PL-dECM demonstrated a sustained supportive effect on PLDSCs and promoted odontogenic/angiogenic differentiation. Both and studies illustrated that PL-dECM served as an effective scaffold for pulp tissue engineering, providing valuable insights into PLDSCs differentiation. These findings pave avenues for the clinical application of dECM's in situ transplantation for regenerative endodontics.
PubMed: 38872841
DOI: 10.1093/rb/rbae050 -
Cureus May 2024A radicular cyst is characterized as an odontogenic cyst of inflammatory origin that develops from Malassez epithelial rests in the periodontal ligament as the...
A radicular cyst is characterized as an odontogenic cyst of inflammatory origin that develops from Malassez epithelial rests in the periodontal ligament as the consequence of dental pulp inflammation. The cyst commenced in the carious tooth and spread to the periodontal and periapical regions. The majority of these lesions appear as precise radiolucencies and encompass their entire apex. The cystic lesion, which is also called a root-end cyst or periapical cyst, is sometimes referred to as a true cyst because it is lined by fluid epithelium. There are several treatment options to address radicular cysts, including surgical and nonsurgical methods. In this case study, we described the clinical observation of the cyst. The cyst typically manifests in later life due to its prolonged etiology. The maxillary anterior region is the most frequently utilized site.
PubMed: 38872665
DOI: 10.7759/cureus.60269 -
Cureus May 2024Traditionally, radiographs were used to assess the working length of root canals. However, the use of Electronic Apex Locators (EAL) may be a non-invasive alternative....
INTRODUCTION
Traditionally, radiographs were used to assess the working length of root canals. However, the use of Electronic Apex Locators (EAL) may be a non-invasive alternative. This study aimed to evaluate the accuracy of the electronic apex locator (EAL) compared to radiographic measurements in determining the working length of root canals.
METHOD
The study assessed the performance of EALs in different scenarios, including the presence of blood and pulp tissue, the use of ethylenediaminetetraacetic acid (EDTA), sodium hypochlorite (NaOCl) as an irrigant, and post-instrumentation with normal saline. An electronic apex locator (DTE DPEX-V; Woodpecker, China) was used alongside traditional radiographs to measure the working length in 144 root canal treatments. Bland-Altman analysis was used to compare the measurements between EAL and radiographs using Jamovi software, v2.4.8 (https://www.jamovi.org/).
RESULT
The findings revealed strong correlations between EAL and radiographic measurements across all testing environments, with Pearson's correlation coefficients ranging from 0.944 to 0.998. The Bland-Altman analysis suggests bias; the average difference was negative and close to zero (Pulp: -0.354, EDTA: -0.0972, NaOCl: -0.0382, Saline: -0.0139) when EAL measurements were compared to radiographic measurements.
CONCLUSION
The working length measurement of root canals using an electronic apex locator such as DTE DPEX-V is comparable to traditional radiographic measurements. The use of irrigants improves the measurement. The EAL has the potential to be an alternative to the invasive radiograph for root canal length measurement.
PubMed: 38872664
DOI: 10.7759/cureus.60283 -
Biomedicine & Pharmacotherapy =... Jul 2024Pulp therapy has been emerged as a one of the efficient therapies in the field of endodontics. Among different types of new endodontic materials, pulpotec has been...
Pulp therapy has been emerged as a one of the efficient therapies in the field of endodontics. Among different types of new endodontic materials, pulpotec has been materialized as a recognized material for vital pulp therapy. However, its efficacy has been challenged due to lack of information about its cellular biocompatibility. This study evaluates the mechanistic biocompatibility of pulpotec cement with macrophage cells (RAW 264.7) at cellular and molecular level. The biocompatibility was evaluated using experimental and computational techniques like MTT assay, oxidative stress analysis and apoptosis analysis through flow cytometry and fluorescent microscopy. The results showed concentration-dependent cytotoxicity of pulpotec cement extract to RAW 264.7 cells with an LC 50 of X/10-X/20. The computational analysis depicted the molecular interaction of pulpotec cement extract components with metabolic proteins like Sod1 and p53. The study revealed the effects of Pulpotec cement's extract, showing a concentration-dependent induction of oxidative stress and apoptosis. These effects were due to influential structural and functional abnormalities in the Sod1 and p53 proteins, caused by their molecular interaction with internalized components of Pulpotec cement. The study provided a detailed view on the utility of Pulpotec in endodontic applications, highlighting its biomedical aspects.
Topics: Oxidative Stress; Apoptosis; Mice; Animals; RAW 264.7 Cells; Macrophages; Biocompatible Materials; Materials Testing; Cell Survival; Tumor Suppressor Protein p53; Dental Cements; Superoxide Dismutase-1
PubMed: 38870628
DOI: 10.1016/j.biopha.2024.116921 -
Porcine Health Management Jun 2024Immediately after birth, newborn piglets fight to establish a teat order. During this process, lesions appear on the piglets' faces and on the sows' teats, which is why...
BACKGROUND
Immediately after birth, newborn piglets fight to establish a teat order. During this process, lesions appear on the piglets' faces and on the sows' teats, which is why tooth resection is carried out on many farms in Germany even though it is known that this procedure is frequently resulting in pulp openings. The opening of a pulp cave is suspected to cause painful tooth alterations and may be an entrance for infectious agents. The purpose of this study was to analyse the effect of tooth resection on skin lesions, development of bodyweight and behaviour in suckling piglets. Four days prepartum, 110 sows in farrow-to-finish production were assigned to one of three treatments. Litters had their teeth left intact (control group, CG), ground with a tea-cup roller head (Tea-cup head grinder group, TCG, Wilofa Diamant, D-56,133 Fachbach, Germany) or ground with a diamond rolling head (rolling head grinder group, RG, IBS/E Company Proxxon GmbH, 54,343 Föhren, Germany). The number of pulp openings in the RG and TCG was examined using a random sample. Piglet body weight and skin lesion scores were recorded within the first 24 h after birth and during each week of the suckling period. Each sow's udder was examined before farrowing, in the second week of lactation and at weaning. The behaviour of the litters from nine sows was video-recorded throughout the suckling period. The aim of this study was to investigate the effects of tooth grinding by a tea-cup head (compared to grinding by a diamond roller head and no grinding [control group]) on the behaviour and average daily gain of piglets as well as on skin lesions on sow udder.
RESULTS
The number of dental injuries was significantly greater in the RG than in the TCG (p < 0.01). Head lesions on piglets were significantly more common in the CG than in the RG (p = 0. 02). Compared to CG piglets, TCG piglets had a significantly greater weight at the end of the suckling period (p = 0.02). No significant difference between treatments was found in the sows' udder (parenchyma, skin, or teat) or in the behaviour of the litters.
CONCLUSION
As tooth grinding is frequently inducing pulp openings, the necessity of the procedure should be carefully and critically scrutinised. In case tooth resection seems inevitable until the underlying management problems have been solved, the Tea-cup grinding head should be used due to significantly fewer pulp openings.
PubMed: 38867344
DOI: 10.1186/s40813-024-00373-x