01836nas a2200205   4500008004100000245007900041210006900120260001200189520120800201653001901409100001801428700001401446700001401460700001701474700001501491700001901506700001501525700001301540856007701553       2018                        eng d00aSystemic and vascular inflammation in an in-vitro model of central obesity0 aSystemic and vascular inflammation in an invitro model of centra  c02/20183 a<p>Metabolic disorders due to over-nutrition are a major global health problem, often associated with obesity and related morbidities. Obesity is peculiar to humans, as it is associated with lifestyle and diet, and so difficult to reproduce in animal models. Here we describe a model of human central adiposity based on a 3-tissue system consisting of a series of interconnected fluidic modules. Given the causal link between obesity and systemic inflammation, we focused primarily on pro-inflammatory markers, examining the similarities and differences between the 3-tissue model and evidence from human studies in the literature. When challenged with high levels of adiposity, the in-vitro system manifests cardiovascular stress through expression of E-selectin and von Willebrand factor as well as systemic inflammation (expressing IL-6 and MCP-1) as observed in humans. Interestingly, most of the responses are dependent on the synergic interaction between adiposity and the presence of multiple tissue types. The set-up has the potential to reduce animal experiments in obesity research and may help unravel specific cellular mechanisms which underlie tissue response to nutritional overload.</p>
10aBioengineering1 aAhluwalia, A.1 aMisto, A.1 aVozzi, G.1 aMagliaro, C.1 aMattei, G.1 aMC, Marescotti1 aAVOGARO, A1 aIori, E.  uhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.019282402269nas a2200229   4500008003900000245008800039210006900127260002700196300000700223520152800230653001901758100001801777700001401795700001401809700001801823700001401841700001501855700001401870700001401884700001701898856012401915       2014                          d00aAutonomous bioreactor modules for disease models and detection of systemic toxicity0 aAutonomous bioreactor modules for disease models and detection o  aPrague, Czech Republic  a433 a<p>Advanced systems based on bioreactors and scaffolds are an essential step towards the development of more predictive and ethical alternatives to animal experiments. Size, modularity, automation, monitoring and essential design are crucial because these elements will ease the transition from old technology and accelerate their acceptance into mainstream research. Based on these requirements, the interconnected transparent sensorised â€œlegoâ€ bioreactors designed in our labs have been used to generate physiologically relevant disease and toxicity models which recapitulate systemic responses impossible to observe in standard cell cultures. The disease model is an interconnected bioreactor circuit with i) adipose tissue in 3D in 3 different concentrations representing normo-weight, over weight and obese body mass indices, ii) human hepatocytes on porous collagen scaffolds and iii) monolayers of human endothelial cells. High adiposity and elevated glucose levels induce systemic and endothelial inflammation in the circuit, as observed in overweight and diabetic humans (Iori et al., 2012). Using similar technology a three-tissue circuit for monitoring the absorption, distribution, metabolism and toxicity of nanoparticles was developed in the context of the EU project InLiveTox (Ucciferri et al., 2014). The results were strikingly similar to those observed in animal experiments demonstrating that the dynamic 3D in-vitro models are ethical, meaningful and economically viable replacements.</p>
10aBioengineering1 aAhluwalia, A.1 aGiusti, S1 aSbrana, T1 aWilkinson, M.1 aMisto, A.1 aLehr, C -M1 aLiley, M.1 aHorst, S.1 aJírová, D.  uhttp://175973.jxltd.asia/publications/autonomous-bioreactor-modules-disease-models-and-detection-systemic-toxicity.html