Publication Date
9-1-2021
Journal
American Journal of Physiology-Gastrointestinal and Liver Physiology
DOI
10.1152/ajpgi.00177.2021
PMID
34288725
PMCID
PMC8461792
PubMedCentral® Posted Date
7-21-2021
PubMedCentral® Full Text Version
Post-Print
Published Open-Access
no
Keywords
Cell Differentiation, Cells, Cultured, Enterohepatic Circulation, Humans, Intestines, Liver, Organoids, Stem Cells, Stomach, bile, FGF19, intestine, liver, organoid
Abstract
The use of human tissue stem cell-derived organoids has advanced our knowledge of human physiological and pathophysiological processes that are unable to be studied using other model systems. Increased 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 fibroblast growth factor 19 (FGF19) (intestine) and downregulation of P450 enzyme cholesterol 7 α-hydroxylase (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.
Graphical Abstract
Included in
Digestive System Diseases Commons, Gastroenterology Commons, Hepatology Commons, Medical Sciences Commons