Biomechanical tensile behavior of human Wharton's jelly.

Wharton's jelly (WJ) is a mucous connective tissue of the umbilical cord. It shows high healing capabilities, mainly attributed to the chemical composition and to the presence of stem cells, growth factors and peptides. Although WJ biological properties are well documented in vitro and in vivo, there is still a lack of mechanical data on this tissue, which is paramount for its use as a biomaterial for medical applications. In this study, mechanical responses of ten WJ samples within close physiological conditions were registered undergoing quasi static cyclic tensile tests followed by a load up to failure. This protocol aimed on one hand to provide biomechanical data to feed predictive numerical models and on the other hand increase WJ knowledge in view of its potential use in biomedical field. In spite of the WJ harvest, the resulting viscous nonlinear elastic response obtained is fully in tune with the literature confirming the database quality. A side of the knowledge improvement on WJ mechanical response, this paper provides accurate data that will enhance predictive simulation work such as finite element analysis. The mechanical step-through brought by the analytical nonlinear characterization over cyclic and ultimate loads is to predict WJ behavior. Actually, principal component analysis highlighted its quality while pointing out indicators, such as failure or hydration criteria, as well as models' limitations.

Osteoclastogenesis and sphingosine-1-phosphate secretion from human osteoclast precursor monocytes are modulated by the cystic fibrosis transmembrane conductance regulator.

Osteopenia and increased fracture rates are well-recognized in patients with cystic fibrosis (CF) disease. In CF pathology, F508del is the most common CFTR mutation, with more than 85% of patients carrying it on at least one allele. The underlying molecular defect in CFTR caused by the F508del-CFTR mutation in osteoclastogenesis, i.e., on the generation and bone-resorption activity of osteoclasts (OCs) from peripheral blood-derived monocytes (PBMCs) remained unexplored. We therefore investigated whether the F508del mutation could affect the osteoclastogenic capacity of PBMCs collected from 15 adult patients bearing the F508del-CFTR mutation, to modulate their bone-resorptive abilities and the level of sphingosine-1-phosphate (S1P) produced by OCs, a key factor in the bone mineral density and formation. In the present study, a severe, defective differentiation of CF-F508del PBMCs to CF-F508del OCs without any significant difference in nuclei number per OC was found compared to non-CF healthy PBMCs from 13 subjects after 7-14-days culture periods. We observed a reduced number of formed non-CF healthy OCs in the presence of a selective inhibitor of CFTR chloride conductance (CFTR-Inh172). Our data regarding OCs resorptive capabilites revealed that a loss of CFTR chloride activity in OCs led to a marked reduction in their trench-resorption mode. A 7-fold increase of the S1P release by CF-F508del OCs was found compared to non-CF healthy OCs after a 21-days culture period. We hypothesize that defective maturation of F508del-OCs precursor monocytes associated with high S1P production in the bone environment might contribute to low bone mineral density observed in the CF population.

Infection of Human Dental Pulp Stromal Cells by Streptococcus mutans: Shedding Light on Bacteria Pathogenicity and Pulp Inflammation.

Cariogenic Streptococcus mutans (S. mutans) is implicated in the dental pulp necrosis but also in cardiovascular tissue infections. Herein, the purpose was to elucidate how human dental pulp derived stromal cells (DPSCs) react toward a direct interaction with S. mutans. DPSCs were challenged with S. mutans. Following 3 h of interaction, DPSCs were able to internalize S. mutans (rate < 1%), and F-actin fibers played a significant role in this process. S. mutans persisted in the DPSCs for 48 h without causing a cytotoxic effect. S. mutans was, however, able to get out of the DPSCs cytoplasm and to proliferate in the extracellular environment. Yet, we noticed several adaptive responses of bacteria to the extracellular environment such as a modification of the kinetic growth, the increase in biofilm formation on type I collagen and polyester fabrics, as well as a tolerance toward amoxicillin. In response to infection, DPSCs adopted a proinflammatory profile by increasing the secretion of IL-8, lL-1ß, and TNF-α, strengthening the establishment of the dental pulp inflammation. Overall, these findings showed a direct impact of S. mutans on DPSCs, providing new insights into the potential role of S. mutans in infective diseases.

Osteoinductive Material to Fine-Tune Paracrine Crosstalk of Mesenchymal Stem Cells With Endothelial Cells and Osteoblasts.

While stem cell/biomaterial studies provide solid evidences that biomaterial intrinsic cues deeply affect cell fate, current strategies tend to neglect their effects on mesenchymal stem cells (MSCs) secretory activities and resulting cell-crosstalks. The present study aims to investigate the impact of bone-mimetic material (B-MM), with intrinsic osteoinductive property, on MSCs mediator secretions; and to explore underlying effects on cells involved in bone regeneration. Human MSCs were cultured, on B-MM, made from inorganic calcium phosphate supplemented with chitosan and hyaluronic acid biopolymers. Collected MSCs culture media were assessed for mediators release quantification and used further to stimulate endothelial cells (ECs) and alveolar bone derived osteoblasts (OBs). Without osteogenic supplements, MSCs committed into bone lineage forming thus 3D bone-like nodules after 21 days. Despite a weak percentage of cell commitment, our data elucidate new aspects of osteoinductive material effect on MSCs functions through the regulation of the secretion of mediators involved in bone regeneration and subsequently the MSCs/ECs indirect crosstalk with osteogenesis-boosting effect. Using MSCs culture media, we demonstrate a large potential of osteoinductive materials and MSCs in bone regenerative medicine. Such strategies could help to address some insights in cell-free therapies using MSCs derived media.

Cationic antimicrobial peptides and periodontal physiopathology: A systematic review.

The purpose of this systematic review was to establish if patients suffering from periodontal diseases present differences in the expression or production of cationic antimicrobial peptides in saliva, gingival fluid, and periodontal tissues. Periodontal diseases are among the most common chronic diseases worldwide and share similar etiological or risk factors (genetic and/or environmental) with other systemic disorders. Over the last decade, an increasing number of publications have suggested the implication of antimicrobial peptides (AMPs) in periodontal and oral tissues conditions. Literature searches were conducted through MEDLINE-PubMed and EMBASE databases which identified 1267 publications. Only clinical studies that focused on assays of the expression and/or production of AMPs in human adult oral fluids (gingival crevicular fluid or saliva) or in oral tissues were retained and finally seventy-four publications meeting inclusion criteria were included. Cathelicidin, α- and ß-defensins 1-3 are the most documented AMPs regarding periodontal status. Significant correlations between clinical periodontal indexes (PD, CAL) and/or bacteriological index and LL37 level were retrieved. Data remain inconsistent between the studies for hBDs mainly due to heterogeneity of the results, periodontal disease diagnostic criteria and assaying technique employed. Given their role in innate immunity and their antimicrobial functions, LL-37 and α-defensins may be eligible as periodontal clinical biomarkers and could be an interesting way for therapeutic development.

Oral plexiform schwannoma: A case report and relevant immunohistochemical investigation.

Schwannomas are benign peripheral nerve sheath tumors originating from the Schwann cells. Most schwannomas in the head and neck region are solitary; however, multiple schwannomas affecting one or more nerves suggest a possible association with neurofibromatosis type 2 and schwannomatosis. Plexiform schwannoma is a rare variant of conventional schwannoma that is characterized by intraneural multinodular growth. This grow pattern has also been observed with other neural tumors which may make diagnosis more difficult. Herein, we report the case of a 28-year-old woman who presented a solitary plexiform schwannoma of great palatine nerve. In the present case, we focused on immunohistochemical analysis in daily practice for the differential diagnosis of schwannomas and their mainly morphological mimics, especially with plexiform neurofibroma, granular cell tumor and malignant peripheral nerve sheath tumors. We also discussed on SMARBC1/IN1 marker usefulness in combination with brain magnetic resonance imaging for the distinction of solitary schwannoma from neurofibromatosis type 2 or schwannomatosis.

Antimicrobial peptide gene expression in periodontitis patients: A pilot study.

AIM: Antimicrobial peptides (AMPs) are one of the most active components of innate immunity and have characteristics that could place them at the heart of the pathogenesis of periodontal disease. This study investigated differences in the expression of AMP coding genes obtained using a simple harvesting technique, gingival smear, between two groups of patients: chronic periodontitis subjects versus healthy ones. MATERIALS AND METHODS: Twenty-three patients were enrolled in two groups: 12 were diagnosed with moderate or severe generalized chronic periodontitis, and 11 were diagnosed as clinically healthy. Gingival smears were retrieved and studied using reverse transcription-quantitative PCR (RT-qPCR) after mRNA purification. RESULTS: Fifteen gene expressions were obtained using real-time RT-qPCR. Three AMP genes, histatin 3 (HTN3), α-defensin 4 (DEFA4) and lysozyme C (LYZ), presented different expression levels in periodontitis patients compared with healthy subjects. The relative expression level of DEFA4 appeared to be a protective factor against periodontitis. CONCLUSION: Gingival smears studied by RT-qPCR may be used to assess the expression of AMPs coding genes. A lack of expression of DEFA4 could be a potential indicator of periodontitis status.