Head circumference and anthropometric changes and their relation to plexiform and skin neurofibromas in sporadic and familial neurofibromatosis 1 Brazilian adults: a cross-sectional study.

BACKGROUND: Neurofibromatosis 1 (NF1) is a common autosomal dominant syndrome with complete penetrance and highly variable expressivity. The cutaneous neurofibroma (Cnf) and plexiform neurofibroma (Pnf), café-au-lait spots, and freckle-like lesions are common in NF1, but many other manifestations can occur. We aimed to evaluate head circumference, height, weight, body mass index (BMI), head circumference-to-height ratio (HCHR) and waist-hip ratio (WHR) in adult NF1 Brazilian individuals versus a paired control group and investigate their correlation with the presence of clinically visible Pnfs, and number of "skin neurofibromas" (Snf), which include both cutaneous and subcutaneous neurofibromas. METHODS: A case-control study was conducted with 168 individuals, 84 with NF1 and 84 without NF1, paired by sex and age. Head circumference and anthropometric measurements, Snf quantification, evaluation of clinically visible Pnf and familial inheritance were accessed. RESULTS: Prevalence of macrocephaly was significantly higher in NF1 women. Height and weight were significantly lower in both males and females with NF1. HCHR was higher in the NF1 group than in the control group for both sexes. BMI was significantly lower in men with NF1. Waist and hip circumferences were significantly reduced in NF compared with the controls, but the mean WHR was significantly lower only in NF1 women. No correlation was found between the Snf and head circumference and anthropometric measurements, sex or family history. The presence and larger size of clinically visible plexiform neurofibromas were associated with normal stature (p = 0.037 and p = 0.003, respectively). CONCLUSIONS: NF1 individuals have increased prevalence of macrocephaly, short stature, low BMI, and reduced abdominal fat. There is no relation between head circumference and anthropometric data with family history, or neurofibromas.

Increased extracellular matrix deposition during chondrogenic differentiation of dental pulp stem cells from individuals with neurofibromatosis type 1: an in vitro 2D and 3D study.

BACKGROUND: Neurofibromatosis 1 (NF1) presents a wide range of clinical manifestations, including bone alterations. Studies that seek to understand cellular and molecular mechanisms underlying NF1 orthopedic problems are of great importance to better understand the pathogenesis and the development of new therapies. Dental pulp stem cells (DPSCs) are being used as an in vitro model for several diseases and appear as a suitable model for NF1. The aim of this study was to evaluate in vitro chondrogenic differentiation of DPSCs from individuals with NF1 using two-dimensional (2D) and three-dimensional (3D) cultures. RESULTS: To fulfill the criteria of the International Society for Cellular Therapy, DPSCs were characterized by surface antigen expression and by their multipotentiality, being induced to differentiate towards adipogenic, osteogenic, and chondrogenic lineages in 2D cultures. Both DPSCs from individuals with NF1 (NF1 DPSCs) and control cultures were positive for CD90, CD105, CD146 and negative for CD13, CD14, CD45 and CD271, and successfully differentiated after the protocols. Chondrogenic differentiation was evaluated in 2D and in 3D (pellet) cultures, which were further evaluated by optical microscopy and transmission electron microscopy (TEM). 2D cultures showed greater extracellular matrix deposition in NF1 DPSCs comparing with controls during chondrogenic differentiation. In semithin sections, control pellets hadhomogenous-sized intra and extracelullar matrix vesicles, whereas NF1 cultures had matrix vesicles of different sizes. TEM analysis showed higher amount of collagen fibers in NF1 cultures compared with control cultures. CONCLUSION: NF1 DPSCs presented increased extracellular matrix deposition during chondrogenic differentiation, which could be related to skeletal changes in individuals with NF1.

Dental stem cells and their application in Dentistry: a literature review

Objective: the aim of this study was to conduct a literature review of the types of stem cells of dental origin and their applications in Dentistry. Material and Methods: for this, we selected scientific articles published between 2000 and 2016 through the databases PUBMED and LILACS. Results: there are five main sources of stem cells of dental origin: stem cells from dental pulp of permanent teeth and deciduous teeth, apical papilla, periodontal ligament and dental follicle. These cells have been studied for the treatment of periodontitis, bone repair, regeneration of the pulp after necrosis as well as the development of new teeth. Conclusion: stem cells from dental origin are an interesting alternative for research and application in regenerative therapies in Dentistry.

High prevalence of hyposalivation in individuals with neurofibromatosis 1: a case-control study.

BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common genetic diseases in humans and has widely variable expressivity. Oral manifestations are common, but there are no studies that investigated functional alterations in salivary glands in NF1. Our aim was to evaluate the salivary flow rate in NF1 individuals, comparing to a control group, and to investigate the possible causes and some consequences of salivary gland alteration. METHODS: This is a case-control study that evaluated the salivary flow rate of NF1 individuals (n = 49) and compared to an age and sex-matched control group. We have also investigated the possible causes and consequences of hyposalivation in NF1 individuals through anamnesis, a specific questionnaire, physical examination, tongue coating evaluation and cytopathological exam to assess the prevalence of oral candidiasis. RESULTS: Hyposalivation at rest was present in 59% (29/49) of NF1 individuals in contrast to 22% (11/49) in the control group, being statistically significant (P <0.0001; Wilcoxon rank-sum test). The analysis of the adjusted residual showed that the prevalence of hyposalivation in NF1 individuals (46.9%) was 4-fold higher than in controls (10.2%). None of the possible causes of hyposalivation (medications, low liquid intake, caffeinated or stimulant drink use, mouth breathers, alcohol, smoke and plexiform neurofibroma close to or involving major salivary glands areas) had important impact on the salivary flow rate in NF1 individuals. CONCLUSIONS: Hyposalivation may be a consequence of NF1, as occurs in other genetic diseases. More studies are necessary to understand if there is and what is the relationship between NF1 and hyposalivation.

Proposing the use of dental pulp stem cells as a suitable biological model of neurofibromatosis type 1.

PURPOSE: This study aims to propose the dental pulp stem cells (DPSCs) as a model for studying two features related to neurofibromatosis type 1 (NF1), i.e. augmented proliferative capacity and altered osteogenic differentiation. METHODS: We isolated a DPSC from the pulp of deciduous teeth of a 6-year-old NF1 patient and two other healthy children of similar age. Cell proliferation was assayed by counting with a haemocytometer after successive cell re-plating. In order to compare osteogenic differentiation, we used osteoblast-differentiating medium and quantified alizarin stain, which relates to degree of calcification, and evaluated the expression of osteoblastic markers by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The DPSCs isolated from the NF1 patient displayed a greater rate of proliferation when compared to the control cells. Osteogenic differentiation occurred as expected for both NF1 and control, which concerned cell morphology and expression of osteoblast marker genes ALP, BMP2, BMP4, OCN and SPP1. However, alizarin staining denoted a markedly lower calcification level in the cells from the NF1-diagnosed child, considering that less calcium deposits were visualized under light microscopy and a smaller amount of alizarin could be quantified by spectrophotometry after extraction from the stained cells. CONCLUSION: DPSCs seem to be useful as a model for studying NF1 and predicting prognosis of patients, since their in vitro behaviour seems to mimic at least two features of this disorder: higher tendency to develop bone abnormalities and neoplastic cell proliferation.

Toward personalized cell therapies by using stem cells: seven relevant topics for safety and success in stem cell therapy.

Stem cells, both embryonic and adult, due to the potential for application in tissue regeneration have been the target of interest to the world scientific community. In fact, stem cells can be considered revolutionary in the field of medicine, especially in the treatment of a wide range of human diseases. However, caution is needed in the clinical application of such cells and this is an issue that demands more studies. This paper will discuss some controversial issues of importance for achieving cell therapy safety and success. Particularly, the following aspects of stem cell biology will be presented: methods for stem cells culture, teratogenic or tumorigenic potential, cellular dose, proliferation, senescence, karyotyping, and immunosuppressive activity.