Guiding the osteogenic fate of mouse and human mesenchymal stem cells through feedback system control.

Stem cell-based disease modeling presents unique opportunities for mechanistic elucidation and therapeutic targeting. The stable induction of fate-specific differentiation is an essential prerequisite for stem cell-based strategy. Bone morphogenetic protein 2 (BMP-2) initiates receptor-regulated Smad phosphorylation, leading to the osteogenic differentiation of mesenchymal stromal/stem cells (MSC) in vitro; however, it requires supra-physiological concentrations, presenting a bottleneck problem for large-scale drug screening. Here, we report the use of a double-objective feedback system control (FSC) with a differential evolution (DE) algorithm to identify osteogenic cocktails of extrinsic factors. Cocktails containing significantly reduced doses of BMP-2 in combination with physiologically relevant doses of dexamethasone, ascorbic acid, beta-glycerophosphate, heparin, retinoic acid and vitamin D achieved accelerated in vitro mineralization of mouse and human MSC. These results provide insight into constructive approaches of FSC to determine the applicable functional and physiological environment for MSC in disease modeling, drug screening and tissue engineering

Urban air pollution, climate and its impact on asthma morbidity

AbstractObjectiveTo study the mechanism of formation of air quality and to determine the impact of the studied factors on asthma morbidity in Vladivostok.MethodsThe evaluation of air pollution in Vladivostok was done using long-term (2008–2012) monitoring data (temperature, humidity, atmospheric pressure, wind speed, etc.). The levels of suspended particulate matter, nitrogen and sulfur dioxide, carbon monoxide, ammonia, formaldehyde (mg/m3) in six stationary observation posts were assessed. We studied the aerosol suspensions of solid particles, which were collected during snowfall from precipitation (snow) and air in 14 districts with different levels of anthropogenic impact. Melted snow was analyzed on laser granulometry. The impact of air pollution on the distribution of asthma morbidity was evaluated in various age groups by data of federal statistical observation obtained from 8 adults and 7 children municipal clinics in Vladivostok (2008–2012).ResultsThe content of suspended particulate components of pollution remained more stable, due to the features of atmospheric circulation, rugged terrain and residential development. The nano- and micro-sized particles (0–50 μm), which can absorb highly toxic metals, prevail in dust aerosols. These respirable fractions of particles, even in small doses, can contribute to the increase in asthma morbidity in the city.ConclusionsWe determined that asthma morbidity depends from general air pollution (in the range of 18.3%). It was detected that the highest age-specific dependence is associated with the content of particulate matter, carbon monoxide and nitrogen dioxide in air