TY - JOUR
AU - Alexandra Sontheimer-Phelps
AU - David B. Chou
AU - Alessio Tovaglieri
AU - Thomas C. Ferrante
AU - Taylor Duckworth
AU - Cicely Fadel
AU - Viktoras Frismantas
AU - Arlene D. Sutherland
AU - Sasan Jalili-Firoozinezhad
AU - Magdalena Kasendra
AU - Eric Stas
AU - James C. Weaver
AU - Camilla A. Richmond
AU - Oren Levy
AU - Rachelle Prantil-Baun
AU - David T. Breault
AU - Donald E. Ingber
AB - METHODS: A human colon-on-a-chip (Colon Chip) microfluidic device lined by primary patient-derived colonic epithelial cells was used to recapitulate mucus bilayer formation, and to visualize mucus accumulation in living cultures noninvasively.
RESULTS: The Colon Chip supports spontaneous goblet cell differentiation and accumulation of a mucus bilayer with impenetrable and penetrable layers, and a thickness similar to that observed in the human colon, while maintaining a subpopulation of proliferative epithelial cells. Live imaging of the mucus layer formation on-chip showed that stimulation of the colonic epithelium with prostaglandin E2, which is increased during inflammation, causes rapid mucus volume expansion via an Na-K-Cl cotransporter 1 ion channel–dependent increase in its hydration state, but no increase in de novo mucus secretion.
CONCLUSIONS: This study shows the production of colonic mucus with a physiologically relevant bilayer structure in vitro, which can be analyzed in real time noninvasively. The Colon Chip may offer a new preclinical tool to analyze
BT - Cellular and Molecular Gastroenterology and Hepatology
DA - 2020
DO - 10.1016/j.jcmgh.2019.11.008
IS - 3
LA - en
N2 - METHODS: A human colon-on-a-chip (Colon Chip) microfluidic device lined by primary patient-derived colonic epithelial cells was used to recapitulate mucus bilayer formation, and to visualize mucus accumulation in living cultures noninvasively.
RESULTS: The Colon Chip supports spontaneous goblet cell differentiation and accumulation of a mucus bilayer with impenetrable and penetrable layers, and a thickness similar to that observed in the human colon, while maintaining a subpopulation of proliferative epithelial cells. Live imaging of the mucus layer formation on-chip showed that stimulation of the colonic epithelium with prostaglandin E2, which is increased during inflammation, causes rapid mucus volume expansion via an Na-K-Cl cotransporter 1 ion channel–dependent increase in its hydration state, but no increase in de novo mucus secretion.
CONCLUSIONS: This study shows the production of colonic mucus with a physiologically relevant bilayer structure in vitro, which can be analyzed in real time noninvasively. The Colon Chip may offer a new preclinical tool to analyze
PY - 2020
SP - 507
EP - 526
T2 - Cellular and Molecular Gastroenterology and Hepatology
TI - Human Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology
UR - https://linkinghub.elsevier.com/retrieve/pii/S2352345X19301638
VL - 9
Y2 - 2022-10-13
SN - 2352345X
ER -