Silicon impacts collagen remodelling and mineralization by human dental pulp stem cells in 3D pulp-like matrices.

OBJECTIVES: Silicon-releasing biomaterials are widely used in the field of dentistry. However, unlike bone, very little is known about the role of silicon on dental tissue formation and repair. This study investigates the influence of silicic acid on the survival, differentiation and mineralizing ability of human dental pulp stem cells (hDPSCs) in 3D pulp-like environments METHODS: Dense type I collagen hydrogels seeded with hDPSCs were cultured over 4 weeks in the presence of silicic acid at physiological (10 µM) and supraphysiological (100 µM) concentrations. Cell viability and proliferation were studied by Alamar Blue and live/dead staining. The collagen network was investigated using second harmonic generation imaging. Mineral deposition was monitored by histology and scanning electron microscopy. Gene expression of mineralization- and matrix remodeling-associated proteins was studied by qPCR. RESULTS: Presence of silicic acid did not show any significant influence on cell survival, metabolic activity and gene expression of key mineralization-related proteins (ALP, OCN, BSP). However, it induced enhanced cell clustering and delayed expression of matrix remodeling-associated proteins (MMP13, Col I). OPN expression and mineral deposition were inhibited at 100 µM. It could be inferred that silicic acid has no direct cellular effect but rather interacts with the collagen network, leading to a modification of the cell-matrix interface. SIGNIFICANCE: Our results offer advanced insights on the possible role of silicic acid, as released by pulp capping calcium silicates biomaterials, in reparative dentine formation. More globally, these results interrogate the possible role of Si in pulp pathophysiology.

CD44, CD90 and CD96 expression in immune thrombocytopenia purpura (ITP) patients.

Studying the expression of hematopoietic stem cell markers from different sources might be useful in understanding stem cell biology in different niche conditions. The study aimed to assess the difference in cell surface markers (CD44, CD90, CD96) on hematopoietic stem cells in three different niche conditions; umbilical cord blood (UCB), normal bone marrow (NBM) and bone marrow samples from idiopathic (immune) thrombocytopenic purpura (IBM). This study was conducted on 300 cases divided into three study groups; 100 umbilical cord blood units collected from mothers undergoing cesarian section in gynecology and obstetrics department, 100 bone marrow samples from idiopathic (immune) thrombocytopenic purpura patients collected from university children hospital and 100 normal bone marrow samples with no evidence of disease in bone marrow tissue. CD44 was significantly elevated in UCB and NBM groups compared to IBM group (<0.001). There was also a significant elevation of CD90 and CD96 in IBM group compared to NBM group and UCB (<0.001). CD90 and CD96 play a role in the pathogenesis of ITP disorder and could be applied as a targeted therapy to improve the outcome of this disease.

NLRP3 Is Involved in Neutrophil Mobilization in Experimental Periodontitis.

The NLRP3 inflammasome is overexpressed in gingiva of periodontitis patients but its role remains unclear. In our study, we use a periodontitis mouse model of ligature, impregnated or not with Porphyromonas gingivalis, in WT or NLRP3 KO mice. After 28 days of induction, ligature alone provoked exacerbated periodontal destruction in KO mice, compared to WT mice, with an increase in activated osteoclasts. No difference was observed at 14 days, suggesting that NLRP3 is involved in regulatory pathways that limit periodontitis. In contrast, in the presence of P. gingivalis, this protective effect of NLRP3 was not observed. Overexpression of NLRP3 in connective tissue of WT mice increased the local production of mature IL-1ß, together with a dramatic mobilization of neutrophils, bipartitely distributed between the site of periodontitis induction and the alveolar bone crest. P. gingivalis enhanced the targeting of NLRP3-positive neutrophils to the alveolar bone crest, suggesting a role for this subpopulation in bone loss. Conversely, in NLRP3 KO mice, mature IL-1ß expression was lower and almost no neutrophils were mobilized. Our study sheds new light on the role of NLRP3 in periodontitis by highlighting the ambiguous role of neutrophils, and P. gingivalis which affects NLRP3 functions.

Differentiation of Cerebral Neoplasms with Vessel Size Imaging (VSI).

PURPOSE: Cerebral neoplasms of various histological origins may show comparable appearances on conventional Magnetic Resonance Imaging (MRI). Vessel size imaging (VSI) is an MRI technique that enables noninvasive assessment of microvasculature by providing quantitative estimates of microvessel size and density. In this study, we evaluated the potential of VSI to differentiate between brain tumor types based on their microvascular morphology. METHODS: Using a clinical 3T MRI scanner, VSI was performed on 25 patients with cerebral neoplasms, 10 with glioblastoma multiforme (GBM), 8 with primary CNS lymphoma (PCNSL) and 7 with cerebral lung cancer metastasis (MLC). Following the postprocessing of VSI maps, mean vessel diameter (vessel size index, vsi) and microvessel density (Q) were compared across tumors, peritumoral areas, and healthy tissues. RESULTS: The MLC tumors have larger and less dense microvasculature compared to PCNSLs in terms of vsi and Q (p = 0.0004 and p < 0.0001, respectively). GBM tumors have higher yet non-significantly different vsi values than PCNSLs (p = 0.065) and non-significant differences in Q. No statistically significant differences in vsi or Q were present between GBMs and MLCs. GBM tumor volume was positively correlated with vsi (r = 0.502, p = 0.0017) and negatively correlated with Q (r = -0.531, p = 0.0007). CONCLUSION: Conventional MRI parameters are helpful in differentiating between PCNSLs, GBMs, and MLCs. Additionally incorporating VSI parameters into the diagnostic protocol could help in further differentiating between PCNSLs and metastases and potentially between PCNSLs and GBMs. Future studies in larger patient cohorts are required to establish diagnostic cut-off values for VSI.