Directional migration and differentiation of neural stem cells within three-dimensional microenvironments.

Harnessing neural stem cells to repair neuronal damage is a promising potential treatment for neuronal diseases. To enable future therapeutic efficacy, the survival, proliferation, migration and differentiation of neural stem/progenitor cells (NPCs) should be accurately studied and optimized in in vitro platforms before transplanting these cells into the body for treatment purposes. Such studies can determine the appropriate quantities of the biochemical and biomechanical factors needed to control and optimize NPC behavior in vivo. In this study, NPCs were cultured within a microfluidic device while being encapsulated within the collagen matrix. The migration and differentiation of NPCs were studied in response to varying concentrations of nerve growth factor (NGF) and within varying densities of collagen matrices. It was shown that the migration and differentiation of NPCs can be significantly improved by providing the appropriate range of NGF concentrations while encapsulating the cells within the collagen matrix of optimal density. In particular, it was observed that within collagen matrices of intermediate density (0.9 mg ml(-1)), NPCs have a higher ability to migrate farther and in a collective manner while their differentiation into neurons is significantly higher and the cells can form protrusions and connections with their neighboring cells. Within collagen matrices with higher densities (1.8 mg ml(-1)), the cells did not migrate significantly as compared to the ones within lower matrix densities; within the matrices with lower collagen densities (0.45 mg ml(-1)) most of the cells migrated in an individual manner. However, no significant differentiation into neurons was observed for these two cases. It was also found that depending on the collagen matrix density, a minimum concentration of NGF caused a collective migration of NPCs, and a minimum concentration gradient of this factor stimulated the directional navigation of the cells. The results of this study can be implemented in designing platforms appropriate for regeneration of damaged neuronal systems.

Parallel in-vitro and in-vivo techniques for optimizing cellular microenvironments by implementing biochemical, biomechanical and electromagnetic stimulations.

Development of novel engineering techniques that can promote new clinical treatments requires implementing multidisciplinary in-vitro and in-vivo approaches. In this study, we have implemented microfluidic devices and in-vivo rat model to study the mechanism of neural stem cell migration and differentiation. These studies can result in the treatment of damages to the neuronal system. In this research, we have shown that by applying appropriate ranges of biochemical and biomechanical factors as well as by exposing the cells to electromagnetic fields, it is possible to improve viability, proliferation, directional migration and differentiation of neural stem cells. The results of this study can be implemented in the design of optimized platforms that can be transplanted into the damaged areas of the neuronal system.

Associations between vitamin D and cardiovascular outcomes; Tehran Lipid and Glucose Study.

BACKGROUND: Vitamin D status seems to have an association with cardiometabolic risk factors and its deficiency may negatively affect the cardiovascular outcomes. The aim of this study was to determine the possible association between vitamin D status and cardiovascular outcomes. METHOD: We performed a nested case control study within the Tehran Lipid and Glucose Study (TLGS), which followed a representative sample of Tehranian adults. A total of 251 matched pairs, aged>30 years, were selected. Cases were TLGS individuals that were free of cardiovascular disease (CVD) at the beginning of study and developed CVD during assessments of 5.7 year follow up. Each case was matched by age, sex and the month of entry to study with a randomly selected control (risk-set sampling). Prespecified cut points were used to characterize varying degrees of 25-OH D deficiency (<10, between 10 and 14.9, and ≥ 15 ng/ml). Conditional logistic regression was used to investigate the association between 25-OH-D concentration and the incident cardiovascular outcomes. RESULTS: The mean age of participants was 56.84 ± 11.17 years and 244 (48.6%) were women. The median (IQ: 25-75) of serum 25-OH-D was 14.1 ng/ml (9.6-29 ng/ml) and 306 (61%) of participants had serum 25-OH-D<15 g/ml. Median serum 25-OH-D was lower in cases (12.5 vs. 18.1, P<0.001). After adjustment for potential confounders, the odds ratio of serum 25-OH-D<10 ng/ml for having CVD outcomes was 2.90 compared with 25-OH-D ≥ 15 (95% confidence interval (CI): 1.67-5.12, P<0.001). CONCLUSION: Our results indicate that serum 25-OH-D concentration has an independent association with cardiovascular outcomes in adult Tehranians.

The effects of air pollution on vitamin D status in healthy women: a cross sectional study.

BACKGROUND: Inadequate radiation or insufficient cutaneous absorption of UVB is one of the cardinal causes of vitamin D deficiency. The aim of this study is to determine whether air pollution and low ground level of ultra-violet B light (UVB; 290-315) can deteriorate the body vitamin D status in healthy women. METHODS: In this cross sectional study 200, free-living, housewives, aged between 20 to 55 years, from Tehran (high polluted area) and Ghazvin (low polluted area) were included. The Tehranian women were selected randomly from participants of the Tehran Lipid and Glucose Study (TLGS) and the Ghazvinian females from patients who came to public health centers. Participants were excluded for disease and drugs which affect vitamin D status and also if they were pregnant or breast feeding. We measured the ground level of UVB using a Haze meter as a surrogate of air pollution. In order to calculate the adjusted mean difference of 25-OH-D, ANCOVA analysis was used. Moreover, Binary logistic regression model was developed to determine the odds of living in Tehran for having serum 25-OH-D less than 20 ng/ml. RESULTS: The mean ± SD of serum 25-OH-D was significantly higher in Ghazvinian women ((18 ± 11 vs. 13 ± 7), P-value < 001). The prevalence of 25-OH-D less than 10 ng/ml, and 25-OH-D between 10 and 20 ng/ml were higher in Tehranian group (36% and 54% vs. 31% and 32% in respectively). Secondary hyperparathyroidism was also significantly higher in Tehranian women (47% vs. 32%). In ANCOVA analysis, after adjustment, the mean of 25-OH-D in the Ghazvinian group was still statistically significantly higher than Tehranians (13 vs. 17 ng/ml P-value = 0.04). In addition, in binary logistic model, the odd of living in Tehran for having serum 25-OH-D less than 20 ng/ml was 5.22 (95% confidence interval 2.2-12.2, P-value < 0.001). CONCLUSION: We found that living in a polluted area plays a significant independent role in vitamin D deficiency and hence, residence can be one of the main reasons of vitamin D status of the women.