In vitro micro-physiological model of the inflamed human adipose tissue for immune-metabolic analysis in type II...

Chronic inflammation mediated by the interaction of immune cells and adipocytes is a key underlying factor in obesity-associated type 2 diabetes mellitus (T2DM). Therefore, methods to investigate adipocyte-immune cells interaction and their immuno-metabolic status in obese/T2DM subjects not only serve as an early indicator of disease development but also provide an insight into disease mechanism. A microfluidic-based in vitro model of the human adipose that is interfaced with a co-culture of immune cell has been developed for in vitro immune-metabolic analysis. This miniaturized system integrates a biologically active in vitro cellular system within a perfusion-based microfluidic device for mimicking the major processes that characterize the interaction of adipose tissue with immune cells. A viable immune competent model of the adipocytes/PBMCs co-culture has been demonstrated and characterized. Our testing results showed that the inflammatory cytokine profile obtained from the on-chip culture agrees with those from static transwell based co-culture with more intense responses observed in the chip-based system. The microfluidic chip also allows time-resolved measurement of cytokines that provide reliable data and detailed mechanisms of inflammation. In addition, glucose uptake by the adipocytes from the chip-based cultures showed correlated insulin responsivity/resistivity to the expression of the cytokine profile in different dynamic culture conditions. Testing of the known diabetic drug, metformin, and neutraceutical compound, omega-3, on-chip show agreeable results as compared to the previously reported data. This organotypic culture system offers a physiologically relevant model that exhibits a key characteristic of type 2 diabetic adipose tissues and can be used to study the T2DM mechanisms and diabetic drug screening.