Adipose-on-a-chip: a dynamic microphysiological in vitro model of the human adipose for immune-metabolic analysis in type II diabetes

Infiltration of immune cells into adipose tissue is associated with chronic low-grade inflammation in obese individuals. To better understand the crosstalk between immune cells and adipocytes, in vivo-like in vitro models are required. Conventionally transwell culture plates are used for studying the adipocyte-immune cell interaction; however, the static culture nature of this approach falls short of closely recapitulating the physiological environment. Here we present a compartmentalized microfluidic co-culture system which provides a constant-rate of nutrient supply as well as waste removal, resembling the microvascular networks of the in vivo environment. Human adipocytes and U937 cells were co-cultured in close proximity in an enclosed system. The porous barrier between the adjacent compartments comprises an array of micro-channels, which enables paracrine interaction between cells in adjacent compartments and improved perfusion-based long term cell feeding. Human pre-adipocytes were fully differentiated into adipocytes on the chip and remained viable for several weeks. Upon co-culturing with immune cells, adipocytes showed a tendency to develop insulin resistance. The immune-metabolic correlation has been studied by monitoring adiponectin and IL-6 expression, as well as glucose uptake upon treatment with insulin. Our microfluidic system can be potentially used to develop physiologically relevant adipose tissue models to study obesity-associated diseases such as insulin resistance and type 2 diabetes and therefore, facilitate drug development to treat these diseases.