AUTHOR=Kakni Panagiota , López-Iglesias Carmen , Truckenmüller Roman , Habibović Pamela , Giselbrecht Stefan 

TITLE=PSC-derived intestinal organoids with apical-out orientation as a tool to study nutrient uptake, drug absorption and metabolism

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1102209

DOI=10.3389/fmolb.2023.1102209

ISSN=2296-889X

ABSTRACT=<p>Intestinal organoids recapitulate many features of the <italic>in vivo</italic> gastrointestinal tract and have revolutionized <italic>in vitro</italic> studies of intestinal function and disease. However, the restricted accessibility of the apical surface of the organoids facing the central lumen (apical-in) limits studies related to nutrient uptake and drug absorption and metabolism. Here, we demonstrate that pluripotent stem cell (PSC)-derived intestinal organoids with reversed epithelial polarity (apical-out) can successfully recapitulate tissue-specific functions. In particular, these apical-out organoids show strong epithelial barrier formation with all the major junctional complexes, nutrient transport and active lipid metabolism. Furthermore, the organoids express drug-metabolizing enzymes and relevant apical and basolateral transporters. The scalable and robust generation of functional, apical-out intestinal organoids lays the foundation for a completely new range of organoid-based high-throughput/high-content <italic>in vitro</italic> applications in the fields of nutrition, metabolism and drug discovery.</p>