(338a) Multi-Organ on Chip Models to Advance Drug Development and Model Disease

There have been tremendous advancements in multi-organ on a chip models, motivated largely by shortcomings of existing simplified in vitro culture models and lack of translation of observations in animal models to humans. Multi-organ on a chip models could be valuable for simulating the human body response to drugs and for modeling disease. The components required for these systems to be useful include: 1. organ models capturing key cell types, architectures, and functions of the organ they are intended to model, here termed microphysiological systems (MPSs), 2. culture platforms enabling controlled maintenance, stimulation, and analysis of MPSs in fluidic communication for multiple weeks, and 3. computational frameworks for relating observations and measurements in these culture systems to function in vivo. This talk will describe advances in these areas, and highlight insight provided by even relatively simple single-(gut) and two-(gut-liver) MPS cultures when integrated with computational systems analysis of soluble factors. The gut, the largest immune organ in the body, is of particular interest given observed relationships between gut homeostasis and varied, numerous conditions including obesity, diabetes, neurodegenerative disorders, and depression. We have developed an immune-competent human intestinal model incorporating representative cellular components of the intestinal mucosal environment (enterocytes, goblet cells and immune cells) to begin to develop a quantitative understanding of how coordinated communication of multiple cell types regulates intestinal homeostasis and its impact on other organ systems, including the liver.