The dental follicle (DF) surrounding the developing tooth germ is an ectomesenchymal tissue composed of various cell populations derived from the cranial neural crest. Human dental follicle cells (HDFC) are believed to contain precursor cells for cementoblasts, periodontal ligament cells, and osteoblasts. Bone morphogenetic proteins (BMPs) produced by Hertwig's epithelial root sheath or present in enamel matrix derivatives (EMD) seem to be involved in the control of DF cell differentiation, but their precise function remains largely unknown. We report the immunolocalization of STRO-1 (a marker of multipotential mesenchymal progenitor cells) and BMP receptors (BMPR) in DF in vivo. In culture, HDFC co-express STRO-1/BMPR and exhibit multilineage properties. Incubation with rhBMP-2 and rhBMP-7 or EMD for 24 h increases the expression of BMP-2 and BMP-7 by HDFC. Long-term stimulation of these cells by rhBMP-2 and/or rhBMP-7 or EMD significantly increases alkaline phosphatase activity (AP) and mineralization. Expression of cementum attachment protein (CAP) and cementum protein-23 (CP-23), two putative cementoblast markers, has been detected in EMD-stimulated whole DF and in cultured HDFC stimulated with EMD or BMP-2 and BMP-7. RhNoggin, a BMP antagonist, abolishes AP activity, mineralization, and CAP/CP-23 expression in HDFC cultures and the expression of BMP-2 and BMP-7 induced by EMD. Phosphorylation of Smad-1 and MAPK is stimulated by EMD or rhBMP-2. However, rhNoggin blocks only Smad-1 phosphorylation under these conditions. Thus, EMD may activate HDFC toward the cementoblastic phenotype, an effect mainly (but not exclusively) involving both exogenous and endogenous BMP-dependent pathways.

Background:Cold-atmospheric plasma (CAP) is an ionized gas produced at an atmospheric pressure. The aim of this systematic review is to map the use of CAP in oncology and the implemented methodologies (cell targets, physical parameters, direct or indirect therapies).Methods:PubMed, the International Clinical Trials Registry Platform and Google Scholar were explored until 31 December 2017 for studies regarding the use of plasma treatment in oncology (in vitro, in vivo, clinical trials).Results:190 original articles were included. Plasma jets are the most-used production systems (72.1%). Helium alone was the most-used gas (35.8%), followed by air (26.3%) and argon (22.1%). Studies were mostly in vitro (94.7%) and concerned direct plasma treatments (84.2%). The most targeted cancer cell lines are human cell lines (87.4%), in particular, in brain cancer (16.3%).Conclusions:This study highlights the multiplicity of means of production and clinical applications of the CAP in oncology. While some devices may be used directly at the bedside, others open the way for the development of new pharmaceutical products that could be generated at an industrial scale. However, its clinical use strongly needs the development of standardized reliable protocols, to determine the more efficient type of plasma for each type of cancer, and its combination with conventional treatments.

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