Bioengineered human colon organoids with in vivo-like cellular complexity and function

Intestine-on-chip enhances nutrient and drug metabolism and maturation of iPSC-derived intestinal epithelial cells relative to organoids and Transwells

“…The elevated expression of nutrient and drug metabolism upon exposure to continuous fluid flow was in concordance with findings from studies using human ASC-derived intestinal epithelial cells: genes associated with lipid, protein and xenobiotic metabolism were upregulated in a human duodenum-derived intestine-on-chip when compared to organoids 9 and in monolayers of duodenal epithelial cells after exposure to rotational flow profiles 13 . Moreover, an ASC-derived colon intestine-on-chip showed upregulation of CYP3A4 when compared to organoids 8 . In addition to enhanced enterocyte functions, microfluidic intestineon-chip systems show potential to study nutrient and drug metabolism and absorption given their easy access to the basolateral and apical side of the epithelial barrier, enlarged epithelial surface area due to the presence of villus-like folds, physiological barrier integrity 15 and ability to sustain dividing and differentiated epithelial subtypes.…”

“…Many studies have investigated the effect of in vitro culture conditions on ASC-derived intestinal epithelial cells, but only limited data is available for hiPSC-derived cells [7][8][9][10]14,34 . In this study, we investigated the controlled induction of hiPSC-derived intestinal epithelial subtypes and the biological processes induced by the culture microenvironment of organoids, Transwell and intestine-on-chip systems.…”

“…The diversity and functioning of intestinal epithelial subtypes in vitro are impacted by exposure to biological and biomechanical cues that emulate intestinal processes, such as growth factor gradients, tissue elasticity or the shear stress imposed by intestinal motions [7][8][9] . To date, most studies investigating the impact of these culture conditions on intestinal epithelial cells have been performed using ASC-derived cells.…”