Review

Authors: J Han, D Menicanin, S Gronthos...

The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing relevant literature that assesses the periodontal-regenerative potential of stem cells. We consider and describe the main stem cell populations that have been utilized with regard to periodontal regeneration, including bone marrow-derived mesenchymal stem cells and the main dental-derived mesenchymal stem cell populations: periodontal ligament stem cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla and dental follicle precursor cells. Research into the use of stem cells for tissue regeneration has the potential to significantly influence periodontal treatment strategies in the future.

Topics: Bone Transplantation; Dental Cementum; Dental Pulp; Dental Sac; Gingiva; Guided Tissue Regeneration, Periodontal; Humans; Intercellular Signaling Peptides and Proteins; Mesenchymal Stem Cells; Periodontal Ligament; Periodontium; Regeneration; Stem Cells; Tissue Engineering; Tissue Scaffolds; Tooth, Deciduous; Wound Healing

PubMed: 24111843
DOI: 10.1111/adj.12100

Comparative Study Review

Authors: G T-J Huang, S Gronthos, S Shi...

To date, 5 different human dental stem/progenitor cells have been isolated and characterized: dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAP), and dental follicle progenitor cells (DFPCs). These postnatal populations have mesenchymal-stem-cell-like (MSC) qualities, including the capacity for self-renewal and multilineage differentiation potential. MSCs derived from bone marrow (BMMSCs) are capable of giving rise to various lineages of cells, such as osteogenic, chondrogenic, adipogenic, myogenic, and neurogenic cells. The dental-tissue-derived stem cells are isolated from specialized tissue with potent capacities to differentiate into odontogenic cells. However, they also have the ability to give rise to other cell lineages similar to, but different in potency from, that of BMMSCs. This article will review the isolation and characterization of the properties of different dental MSC-like populations in comparison with those of other MSCs, such as BMMSCs. Important issues in stem cell biology, such as stem cell niche, homing, and immunoregulation, will also be discussed.

Topics: Bone Marrow Cells; Cell Differentiation; Cell Lineage; Dental Papilla; Dental Pulp; Dental Sac; Humans; Mesenchymal Stem Cells; Periodontal Ligament; Regeneration; Tissue Engineering; Tooth; Tooth, Deciduous

PubMed: 19767575
DOI: 10.1177/0022034509340867

Review

Authors: A Alqerban, R Jacobs, P Lambrechts...

Root resorption of maxillary lateral incisors caused by erupting canines is well known and a relatively common phenomenon. However, much debate and conflicting evidence exists with regard to the actual resorption trigger and potential etiological factors involved. Consequently, there are no obvious clinical clues concerning prevention and diagnosis as well as subsequent treatment decisions. The introduction of cone beam computer tomography has recently allowed drawing a new and much more documented light on the diagnostic and therapeutic strategies. However, no investigations have determined that this new information may result in another and better diagnostic approach and an improved treatment outcome. Therefore, the present review will attempt to summarize the existing evidence on two- and three-dimensional images and try to link the radiological observations to any further preventive, diagnostic, and/or therapeutic measures. Detection thresholds, accuracy, and reliability of impacted canine localization and neighboring root resorption risks will also be considered. This review demonstrates how adding a third-dimension to the radiographic information may notably alter the prevalence of root resorptions and descriptions of this prevalence. In any case, further investigation is needed to determine resorption detection thresholds in various two-dimensional and three-dimensional imaging techniques, as well as to determine therapeutic thresholds and criteria for strategic tooth extraction based on radiographic manifest and not manageable resorption lesions.

Topics: Cone-Beam Computed Tomography; Cuspid; Dental Sac; Humans; Imaging, Three-Dimensional; Incisor; Maxilla; Orthodontics, Corrective; Root Resorption; Tooth Eruption, Ectopic; Tooth, Impacted

PubMed: 19277728
DOI: 10.1007/s00784-009-0262-8

Randomized Controlled Trial

Authors: Arri Coomarasamy, Hoda M Harb, Adam J Devall...

BACKGROUND

Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage.

OBJECTIVES

(1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding.

DESIGN

A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding.

SETTING

A total of 48 hospitals in the UK.

PARTICIPANTS

Women aged 16-39 years with early pregnancy bleeding.

INTERVENTIONS

Women aged 16-39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation.

MAIN OUTCOME MEASURES

The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective.

RESULTS

A total of 4153 women from 48 hospitals in the UK received either progesterone ( = 2079) or placebo ( = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07;  = 0.08). A significant subgroup effect (interaction test  = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04;  = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12;  = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51;  = 0.004). A significant post hoc subgroup effect (interaction test  = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15;  = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (£7655 vs. £7572), with a mean cost difference of £83 (adjusted mean difference £76, 95% confidence interval -£559 to £711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as £3305 per additional live birth at ≥ 34 weeks of gestation.

CONCLUSIONS

Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets.

TRIAL REGISTRATION

Current Controlled Trials ISRCTN14163439, EudraCT 2014-002348-42 and Integrated Research Application System (IRAS) 158326.

FUNDING

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 33. See the NIHR Journals Library website for further project information.

Topics: Abortion, Spontaneous; Adolescent; Adult; Cost-Benefit Analysis; Double-Blind Method; Female; Humans; Parturition; Pregnancy; Pregnancy Trimester, First; Progesterone; Suppositories; United Kingdom; Uterine Hemorrhage; Young Adult

PubMed: 32609084
DOI: 10.3310/hta24330

Randomized Controlled Trial

Authors: Justin J Chu, Adam J Devall, Leanne E Beeson...

BACKGROUND

The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone.

METHODS

MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/mvs ≥35 kg/m), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024.

FINDINGS

Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups.

INTERPRETATION

Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery.

FUNDING

UK National Institute for Health Research Health Technology Assessment Programme.

Topics: Abortion, Missed; Adult; Double-Blind Method; Drug Therapy, Combination; Humans; Mifepristone; Misoprostol; Oxytocics; Treatment Outcome

PubMed: 32853559
DOI: 10.1016/S0140-6736(20)31788-8

Review

Authors: Li Zeng, Hong He, Mingjie Sun...

Dental follicles are necessary for tooth eruption, surround the enamel organ and dental papilla, and regulate both the formation and resorption of alveolar bone. Dental follicle progenitor cells (DFPCs), which are stem cells found in dental follicles, differentiate into different kinds of cells that are necessary for tooth formation and eruption. Runt-related transcription factor 2 (Runx2) is a transcription factor that is essential for osteoblasts and osteoclasts differentiation, as well as bone remodeling. Mutation of Runx2 causing cleidocranial dysplasia negatively affects osteogenesis and the osteoclastic ability of dental follicles, resulting in tooth eruption difficulties. Among a variety of cells and molecules, Nel-like molecule type 1 (Nell-1) plays an important role in neural crest-derived tissues and is strongly expressed in dental follicles. Nell-1 was originally identified in pathologically fused and fusing sutures of patients with unilateral coronal synostosis, and it plays indispensable roles in bone remodeling, including roles in osteoblast differentiation, bone formation and regeneration, craniofacial skeleton development, and the differentiation of many kinds of stem cells. Runx2 was proven to directly target the Nell-1 gene and regulate its expression. These studies suggested that Runx2/Nell-1 axis may play an important role in the process of tooth eruption by affecting DFPCs. Studies on short and long regulatory noncoding RNAs have revealed the complexity of RNA-mediated regulation of gene expression at the posttranscriptional level. This ceRNA network participates in the regulation of Runx2 and Nell-1 gene expression in a complex way. However, non-study indicated the potential connection between Runx2 and Nell-1, and further researches are still needed.

Topics: Bone Remodeling; Calcium-Binding Proteins; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Dental Sac; Humans; Osteogenesis; RNA; Stem Cells; Tooth Eruption; Transcription Factors

PubMed: 36175952
DOI: 10.1186/s13287-022-03140-3

Randomized Controlled Trial

Efficacy and safety of the combination of estetrol 15 mg/drospirenone 3 mg in a cyclic regimen for the treatment of endometriosis-associated pain and objective gynecological findings: a multicenter, placebo-controlled, double-blind, randomized study.

Authors: Tasuku Harada, Takao Kobayashi, Akihiro Hirakawa...

OBJECTIVE

To evaluate the efficacy and safety of 24-week cyclic administration of estetrol (E4) (15 mg)/drospirenone (DRSP) (3 mg) in Japanese patients with endometriosis.

DESIGN

A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.

SETTING

Twenty-five study centers in Japan.

PATIENT(S)

A total of 162 Japanese women diagnosed with endometriosis.

INTERVENTION(S)

Participants were randomly allocated to the E4/DRSP group or the placebo group. In the E4/DRSP group, participants were orally administered one tablet containing E4 (15 mg) and DRSP (3 mg) daily for 24 days, followed by one placebo tablet for 4 days for a hormone-free interval, constituting a 1-cycle regimen. One placebo tablet was administered once daily for 28 days to participants in the placebo group. The treatments were continued for six cycles (24 weeks) throughout the confirmatory period.

MAIN OUTCOME MEASURE(S)

Changes in visual analogue scale (VAS) scores for the most severe pelvic pain (lower abdominal and back pain) from baseline to six treatment cycles at the end of the confirmatory study period.

RESULT(S)

Estetrol/drospirenone showed changes in the mean VAS scores for the most severe pelvic pain (-33.2 mm) from baseline to the end of the 6-cycle treatment. The between-group difference was significant (-8.5 mm; 2-sided 95% confidence interval, -16.1 to -0.9 mm), showing superiority to placebo. The responder rates, ≥30% and ≥50% reductions in the VAS scores from baseline, were higher in the E4/DRSP group than in the placebo group: 53.2% vs. 29.6% and 36.4% vs. 12.3%. Objective gynecological findings (induration of the cul-de-sac, pelvic tenderness, and limited uterine mobility) were significantly improved by E4/DRSP treatment, and the proportions of stable and worsened participants were significantly lower than in the placebo group. Estetrol/drospirenone decreased the size of endometriomas and improved quality of life, on the basis of quality of life-related questionnaires and global impression scores. No safety concerns were observed with E4/DRSP treatment. Few differences were observed in the proportion of participants with hemostasis parameters outside the reference range between the E4/DRSP and placebo groups.

CONCLUSION(S)

Estetrol/drospirenone effectively treats endometriosis-associated pain and improves gynecological findings. Estetrol/drospirenone may be a safe, new option for endometriosis treatment with a potentially decreased risk of thromboembolic events.

CLINICAL TRIAL REGISTRATION NUMBER

jRCT2011210027.

Topics: Humans; Female; Endometriosis; Double-Blind Method; Adult; Androstenes; Treatment Outcome; Pelvic Pain; Estetrol; Pain Measurement; Drug Combinations; Japan; Young Adult; Drug Administration Schedule

PubMed: 39002879
DOI: 10.1016/j.fertnstert.2024.07.011

Review

Authors: Franziska L Ulmer, Andreas Winkel, Philipp Kohorst...

Stem cell biology, an emerging field of research, provides promising methods in vitro as well as in vivo in animal models which make speculation about a future application in human dentistry reasonable. The objective of this study was to review the literature of stem cell research concerning fields relevant for dentistry. In dentistry, different stem cells are discussed. Adult dental ectomesenchymal stem cells seem promising for future therapy. Human stem cells have been isolated from the dental pulp, exfoliated deciduous teeth, the periodontal ligament, the dental follicle and the dental papilla. Stem cell markers such as STRO-1 were used for the characterization and isolation of stem cells. Adult dental stem cells can differentiate into many dental components, such as dentin, periodontal ligament, cement and dental pulp tissue, but not into enamel.

Topics: Adult Stem Cells; Animals; Antigens, Differentiation; Biomarkers; Dental Papilla; Dental Pulp; Dental Sac; Epithelial Cells; Humans; Mesenchymal Stem Cells; Odontogenesis; Periodontal Ligament; Regeneration; Tooth, Deciduous

PubMed: 21207302
DOI: No ID Found

Authors: Ella Ohlsson, Carola Bolay, Sevgi Arabulan...

OBJECTIVES

Although the introduction of self-adhesive composites in restorative dentistry is very promising, the innovation of new materials also presents challenges and unknowns. Therefore, the aim of this study was to investigate the cytotoxicity of four different self-adhesive composites (SAC) in vitro and to compare them with resin-modified glass ionomer cements (RM-GIC), a more established group of materials.

METHODS

Samples of the following materials were prepared according to ISO 7405/10993-12 and eluted in cell culture medium for 24 h at 37 °C: Vertise Flow, Fusio Liquid Dentin, Constic, Surefil One, Photac Fil and Fuji II LC. Primary human pulp cells were obtained from extracted wisdom teeth and cultured for 24 h with the extracts in serial dilutions. Cell viability was evaluated by MTT assay, membrane disruption was quantified by LDH assay and apoptosis was assessed by flow cytometry after annexin/PI staining.

RESULTS

Two SAC (Constic and Vertise Flow) and one RM-GIC (Photac Fil) significantly reduced cell viability by more than 30% compared to the untreated control (p < 0.001). Disruptive cell morphological changes were observed and the cells showed signs of late apoptosis and necrosis in flow cytometry. Membrane disruption was not observed with any of the investigated materials.

CONCLUSION

Toxic effects occurred independently of the substance group and need to be considered in the development of materials with regard to clinical implications.

CLINICAL SIGNIFICANCE

SAC have many beneficial qualities, however, the cytotoxic effects of certain products should be considered when applied in close proximity to the dental pulp, as is often required.

Topics: Humans; Resin Cements; Dental Cements; Composite Resins; Glass Ionomer Cements; Materials Testing; Dental Materials

PubMed: 38403539
DOI: 10.1016/j.dental.2024.02.015