Abstract

Novel Microphysiological Multi-Organ Systems for Studies of Human Metabolic Diseases in Drug Discovery

Tommy Andersson, Senior Principal Scientist, Professor, AstraZeneca Research and Development Molndal

Currently used pre-clinical models often suffer from poor translation of drug responses to the patient due to the limited knowledge gained in the efficiency and mode of action of the drug candidate. This contributes to high attrition rates in early clinical programs. Multi organ-on-a-chip emulating human physiology have the possibility to improve success rate by mimicking the human disease state and improve selection of the right targets and compounds early in drug discovery. Such models will not only improve translation to patients but also reduce time spent in early clinical programs as well as reducing the needs for animal models.  We developed a human liver - pancreatic islets chip model. The model allows cross talk between cells from both organs in a fluidic system and responds in a physiological way to glucose load by increased insulin secretion leading to increased glucose consumption (figure). Initial studies indicate that the model can become insulin resistant and thus can be used as a metabolic disease model.  Ongoing studies are investigating how insulin resistance in liver cells effects islet function by using the insulin receptor antagonists.