02081nas a2200349   4500000000100000000000100001008004100002260000900043100003200052700001800084700002300102700002300125700002100148700001700169700002400186700002500210700003100235700002300266700001400289700002000303700002400323700001400347700002600361700002100387700002100408245011200429856006700541300001200608490000600620520109200626022001301718       2020                            d  c20201 aAlexandra Sontheimer-Phelps1 aDavid B. Chou1 aAlessio Tovaglieri1 aThomas C. Ferrante1 aTaylor Duckworth1 aCicely Fadel1 aViktoras Frismantas1 aArlene D. Sutherland1 aSasan Jalili-Firoozinezhad1 aMagdalena Kasendra1 aEric Stas1 aJames C. Weaver1 aCamilla A. Richmond1 aOren Levy1 aRachelle Prantil-Baun1 aDavid T. Breault1 aDonald E. Ingber00aHuman Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology  uhttps://linkinghub.elsevier.com/retrieve/pii/S2352345X19301638  a507-5260 v93 aMETHODS: 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  a2352345X