Use of Human Tissue Stem Cell-Derived Organoid Cultures to Model Enterohepatic Circulation
The use of human tissue stem cell-derived organoids has advanced our knowledge of human physiologic and pathophysiological processes that are unable to be studied using other model systems. Increases in the understanding of human epithelial tissues including intestine, stomach, liver, pancreas, lung, and brain have been achieved using organoids. However, it is not yet clear whether these cultures recapitulate in vivo organ-to-organ signaling or communication. In this work, we demonstrate that mature stem cell-derived intestinal and liver organoid cultures each express functional molecules that modulate bile acid uptake and recycling. These organoid cultures can be physically coupled in a Transwell® system and display increased secretion of FGF19 (intestine) and downregulation of CYP7A (liver) in response to apical exposure of the intestine to bile acids. This work establishes that organoid cultures can be used to study and therapeutically modulate interorgan interactions and advance the development of personalized approaches to medical care.