Paul Monsarrat

Concise Review: Mesenchymal Stromal Cells Used for Periodontal Regeneration: A Systematic Review

Periodontitis is a chronic infectious disease of the soft and hard tissues supporting the teeth. Recent advances in regenerative medicine and stem cell biology have paved the way for periodontal tissue engineering. Mesenchymal stromal cells (MSCs) delivered in situ to periodontal defects may exert their effects at multiple levels, including neovascularization, immunomodulation, and tissue regeneration. This systematic review had two goals: (a) to objectively quantify key elements for efficacy and safety of MSCs used for periodontal regeneration and (b) to identify patterns in the existing literature to explain differences between studies and suggest recommendations for future research. This systematic review provided good evidence of the capacity of MSCs to regenerate periodontal tissues in animals; however, experimentally generated defects used in animal studies do not sufficiently mimic the pathophysiology of periodontitis in humans. Moreover, the safety of such interventions in humans still needs to be studied. There were marked differences between experimental and control groups that may be influenced by characteristics that are crucial to address before translation to human clinical trials. We suggest that the appropriate combination of cell source, carrier type, and biomolecules, as well as the inclusion of critical path issues for a given clinical case, should be further explored and refined before transitioning to clinical trials. Future studies should investigate periodontal regenerative procedures in animal models, including rodents, in which the defects generated are designed to more accurately reflect the inflammatory status of the host and the shift in their pathogenic microflora.

An Innovative, Comprehensive Mapping and Multiscale Analysis of Registered Trials for Stem Cell-Based Regenerative Medicine

We aim to provide an innovative, comprehensive way of mapping the profusion of stem cell‐based clinical trials registered at ClinicalTrials.gov to explore the diversity of the fields of application and the temporal complexity of the domain. We used a chord diagram and phylogenetic‐like tree visualizations to assist in data mining and knowledge discovery. The search strategy used the following terms: “stromal OR stem OR mesenchymal OR progenitor.” The Medical Subject Headings (MeSH) thesaurus was used to more finely classify diseases treated by stem cells, from large fields of application to specific diseases. Of the 5,788 trials screened, 939 were included, 51.1% of which were related to mesenchymal stem cells (MSCs). No real specificity emerged as to the therapeutic uses of the different types of stem cells. More than half the MSC studies concerned allogeneic MSCs and received more support from industry than autologous MSC studies (p < .001). Over time, the uses of cultured cells have increased greatly, particularly since 2009. Cells derived from adipose tissue are also increasingly used in trials compared with bone marrow cells. The use of adipose‐derived stromal cells was predominantly autologous (p < .001), restricted to European countries (p < .01), and supported by industry (p = .02) compared with other MSCs. Details about MeSH keywords are available at http://multireview.perso.sfr.fr/. In conclusion, mapping may reveal a lack of global strategy despite the regulations and the related costs associated with good manufacturing practices. A systematic approach to preclinical data, intended to objectively and robustly reveal the most appropriate fields with the most efficient cells, is needed. Repeated exchanges between the bench and the bedside are necessary.

Clinical research activity in periodontal medicine: a systematic mapping of trial registers.

AIM The primary aim of the study was to systematically map registration records on periodontal medicine in clinical trial registers. The secondary aim was to assess the evolution of periodontal medicine in clinical periodontal research as a whole. MATERIAL AND METHODS We searched all registration records related to periodontology in the World Health Organization International Clinical Trials Registry Platform. For registration records classified in the field of periodontal medicine, we assigned the 2015 MeSH(®) term for the most precisely corresponding systemic condition. RESULTS Fifty-seven systemic conditions have been hypothesized to be linked with periodontal diseases, covering nearly 2% of the diseases indexed in MeSH. In addition to diabetes, cardiovascular disease or preterm birth, other systemic conditions have been the subject of registration records, such as anaemia, liver diseases, dyspepsia or ankylosing spondylitis. A trend towards increasing diversification of systemic conditions has appeared over time. About a third of registration records in clinical periodontal research deals with periodontal medicine. CONCLUSIONS Periodontal medicine now constitutes an important part of clinical periodontal research. Research activity in periodontal medicine has grown continuously since the early 2000s, and exploration of registers gives a useful up-to-date snapshot of this constantly evolving field of research.

Periodontal Tissue Regeneration Using Syngeneic Adipose-Derived Stromal Cells in a Mouse Model

Current treatment of periodontitis is still associated with a high degree of variability in clinical outcomes. Recent advances in regenerative medicine by mesenchymal cells, including adipose stromal cells (ASC) have paved the way to improved periodontal regeneration (PD) but little is known about the biological processes involved. Here, we aimed to use syngeneic ASCs for periodontal regeneration in a new, relevant, bacteria‐induced periodontitis model in mice. Periodontal defects were induced in female C57BL6/J mice by oral gavage with periodontal pathogens. We grafted 2 × 105 syngeneic mouse ASCs expressing green fluorescent protein (GFP) (GFP+/ASC) within a collagen vehicle in the lingual part of the first lower molar periodontium (experimental) while carrier alone was implanted in the contralateral side (control). Animals were sacrificed 0, 1, 6, and 12 weeks after treatment by GFP+/ASC or vehicle graft, and microscopic examination, immunofluorescence, and innovative bio‐informatics histomorphometry methods were used to reveal deep periodontium changes. From 1 to 6 weeks after surgery, GFP+ cells were identified in the periodontal ligament (PDL), in experimental sites only. After 12 weeks, cementum regeneration, the organization of PDL fibers, the number of PD vessels, and bone morphogenetic protein‐2 and osteopontin expression were greater in experimental sites than in controls. Specific stromal cell subsets were recruited in the newly formed tissue in ASC‐implanted periodontium only. These data suggest that ASC grafting in diseased deep periodontium, relevant to human pathology, induces a significant improvement of the PDL microenvironment, leading to a recovery of tooth‐supporting tissue homeostasis. Stem Cells Translational Medicine 2017;6:656–665

Survival of directly placed ormocer-based restorative materials: A systematic review and meta-analysis of clinical trials

OBJECTIVES In-vitro experiments on ormocers (ORganically MOdified CERamics) have provided controversial results. Consequently, the objectives of this meta-analysis were to (1) compare clinical performances of first generation ormocers versus conventional composite restorations, (2) explore the influence of various clinical factors and the impact of the quality of studies on published results. METHODS The following databases were explored until 2017/01/08: Ovid MEDLINE In-Process, Pubmed, CENTRAL, HTA, DARE, LILACS and Google Scholar. Studies of more than two years with quantitative comparisons between ormocers and control groups were selected. Outcome was the failure of a restoration (need to repair, remove or replace). Multivariate random-effects Poissons regression was used to obtain a summary estimate. RESULTS 75% of the 8 included trials concerned Class I/II restorations. Although non-significant, the global failures were higher for ormocers (0.22 [-0.16; 0.61]). For Class I/II restorations, a significantly higher sensitivity was observed for ormocer-based materials compared to other composites (0.75 [0.01; 1.50]). An increase of the number of restorations per patient was associated with higher marginal adaptation failures for ormocers in Class I/II obturations (0.59 [0.11; 1.08]). SIGNIFICANCE This study did not identify clear advantages of using the first generation of ormocer-based fillings rather than conventional composites. Given the recent development of new, dimethacrylate-diluent-free ormocer matrices, potentially more stable and resistant, new randomized clinical trials should be developed comparing this new family of pure ormocers with current composites.

Comparison between pediatric and adult adipose mesenchymal stromal cells

BACKGROUND Adipose-derived mesenchymalstromal cells (ASC) are currently tested in regenerative medicine to promote tissue reconstruction after injury. Regardingautologous purpose, the possible loss of therapeutic function and cell properties during aging have been questioned in adults. To date no reliable information is available concerning ASC from pediatric patients and a better knowledge is required for clinical applications. METHODS Subcutaneous adipose tissue was collected from 27 donors (0-1 years old) and 50 donors (1-12 years old) and compared with adult ASC for in vitro characteristics. ASC were then tested in a mouse model of limb ischemia. RESULTS Cells from the stromal vascular fraction (SVF) and subsequent cultured ASC were prepared. Only a greater amount in SVF cell number and ASC proliferative rate were found. Cell phenotype, colony formingunit-fibroblast (CFU-F) content, immunomodulation effect and adipogenic, osteoblastic and angiogenic potentials were not significantly different. In vivo, pediatric ASC induced an increase in microangiographic score in a mouse model of limb ischemia, even though improvement in vascular density was not significantly correlated to limb rescue. Finally messengerRNA (mRNA) analysis using a microarray approach identified that only 305 genes were differentially expressed (217 down- and 88 up-regulated) in pediatric versus adult ASC, confirming that ASC from both age groups shared very close intrinsic properties. CONCLUSION This is the first study reporting a comparative analysis of ASC from a large number of donors and showing that their in vitro and in vivo properties were similar and maintained during aging.

Socioeconomic and behavioral determinants of tooth brushing frequency: results from the representative French 2010 HBSC cross‐sectional study

OBJECTIVES To describe tooth brushing frequency and its association with a wide range of socioeconomic and behavioral characteristics, using a nationally representative sample of school-aged children in France. METHODS Our sample included 11,337 students aged from 10 to 16 years, who answered the HBSC questionnaire. Some variables were grouped into composite variables, thus generating scores for: eating habits, health and body, relationships with parents, socioeconomic status (SES) of family, and school life. Multivariate logistic regression analyses were used to study the relationship between these variables and tooth brushing frequency. RESULTS Girls were more likely to brush twice a day than boys [adjusted Odds Ratio: aOR 2.47, 95 percent confidence interval CI95% (1.97; 3.11), aOR 1.89, CI95% (1.56; 2.29), aOR 1.45, CI95% (1.25; 1.68) for low, mid, and high school life score, respectively]. Students were more likely to brush twice a day when they had high (versus low) scores for healthy eating habits [aOR = 1.60; 95 percent CI: (1.40; 1.83)], well-being concerning health and body [aOR = 1.61; 95 percent CI: (1.40; 1.86)] and SES [aOR = 1.25; 95 percent CI: (1.09; 1.43)]. CONCLUSIONS We believe that preventive health campaigns should target school and family environments more specifically to reach the most disadvantaged sections of the population and include promotion of whole health. The messages should be designed to efficiently reach adolescents, e.g., by appealing to their maturity, self-esteem, and emotional factors. Through the incorporation of qualitative research elements, identifying the reasons for not brushing twice a day would also help to develop new prevention programs.

Optimal duration of ultra low frequency-transcutaneous electrical nerve stimulation (ULF-TENS) therapy for muscular relaxation in neuromuscular occlusion: A preliminary clinical study

Objectives: The primary aim of this work was to determine the duration of ultra-low-frequency transcutaneous electrical nerve stimulation (ULF-TENS) application necessary to achieve sufficient relaxation of the masticatory muscles. A secondary aim was to analyze the influence of stimulation on muscle relaxation in pathological subjects and determine whether ULF-TENS has a noteworthy impact on muscle relaxation. Methods: Sixteen adult subjects with temporomandibular disorders (TMD) and muscle pain and a group of four control subjects were included in this study. ULF-TENS was applied, and muscular activities of the masseter, temporal, and sternocleidomastoid muscles (SCM) were recorded for 60 min. Results: Significant relaxation was achieved in the TMD group from 20, 40, and 60 min for the temporal, masseter, and SCM muscles (p < 0.05), respectively. Maximum relaxation was achieved in 12.5% of the subjects after 20 min, in a further 12.5% after 40 min, and in the remaining 75% after 60 min. Significant relaxation was achieved in the control group from 20 to 40 min for the masseter and temporal muscles, respectively (p < 0.05). Discussion: Taken together, the results suggest that an ideal ULF-TENS application would last 40 min to obtain sufficient muscle relaxation both in patients with masticatory system disorders and healthy subjects, a time constraint that is consistent with everyday clinical practice.

Data mining of effect sizes from PubMed abstracts: a cross-study conceptual replication

Data mining of effect sizes from PubMed abstracts: a cross-study conceptual replication Paul Monsarrat and Jean-Noel Vergnes* Department of Anatomical Sciences and Radiology, Dental Faculty, Paul Sabatier University, Toulouse University Hospital (CHU de Toulouse), Toulouse, France, STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, ENVT, Inserm, UPS, Toulouse, France, Department of Epidemiology and Public Health, Dental Faculty, Paul Sabatier University, Toulouse University Hospital (CHU de Toulouse), Toulouse, France and Division of Oral Health and Society, Faculty of Dentistry, McGill University, Montreal, QC, Canada

A geometric morphometric approach to the study of variation of shovel-shaped incisors

OBJECTIVES The scoring and analysis of dental nonmetric traits are predominantly accomplished by using the Arizona State University Dental Anthropology System (ASUDAS), a standard protocol based on strict definitions and three-dimensional dental plaques. However, visual scoring, even when controlled by strict definitions of features, visual reference, and the experience of the observer, includes an unavoidable part of subjectivity. In this methodological contribution, we propose a new quantitative geometric morphometric approach to quickly and efficiently assess the variation of shoveling in modern human maxillary central incisors (UI1). MATERIALS AND METHODS We analyzed 87 modern human UI1s by means of virtual imaging and the ASU-UI1 dental plaque grades using geometric morphometrics by placing semilandmarks on the labial crown aspect. The modern human sample was composed of individuals from Europe, Africa, and Asia and included representatives of all seven grades defined by the ASUDAS method. RESULTS Our results highlighted some limitations in the use of the current UI1 ASUDAS plaque, indicating that it did not necessarily represent an objective gradient of expression of a nonmetric tooth feature. Rating of shoveling tended to be more prone to intra- and interobserver bias for the highest grades. In addition, our analyses suggest that the observers were strongly influenced by the depth of the lingual crown aspect when assessing the shoveling. DISCUSSION In this context, our results provide a reliable and reproducible framework reinforced by statistical results supporting the fact that open scale numerical measurements can complement the ASUDAS method.