02343nas a2200337   4500000000100000000000100001008004100002260001500043653001600058653002800074653002300102100002300125700002300148700003200171700003100203700001400234700002500248700001900273700001600292700001900308700002400327700001000351700002100361700002100382245009200403856005500495300000900550490000600559520142600565022001401991       2018                            d  c2018-02-1310aBiomimetics10aStem-cell biotechnology10aTissue engineering1 aMagdalena Kasendra1 aAlessio Tovaglieri1 aAlexandra Sontheimer-Phelps1 aSasan Jalili-Firoozinezhad1 aAmir Bein1 aAngeliki Chalkiadaki1 aWilliam Scholl1 aCheng Zhang1 aHannah Rickner1 aCamilla A. Richmond1 aHu Li1 aDavid T. Breault1 aDonald E. Ingber00aDevelopment of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids  uhttps://www.nature.com/articles/s41598-018-21201-7  a28710 v83 aHere we describe a method for fabricating a primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The primary epithelial cells are expanded as 3D organoids, dissociated, and cultured on a porous membrane within a microfluidic device with human intestinal microvascular endothelium cultured in a parallel microchannel under flow and cyclic deformation. In the Intestine Chip, the epithelium forms villi-like projections lined by polarized epithelial cells that undergo multi-lineage differentiation similar to that of intestinal organoids, however, these cells expose their apical surfaces to an open lumen and interface with endothelium. Transcriptomic analysis also indicates that the Intestine Chip more closely mimics whole human duodenum in vivo when compared to the duodenal organoids used to create the chips. Because fluids flowing through the lumen of the Intestine Chip can be collected continuously, sequential analysis of fluid samples can be used to quantify nutrient digestion, mucus secretion and establishment of intestinal barrier function over a period of multiple days in vitro. The Intestine Chip therefore may be useful as a research tool for applications where normal intestinal function is crucial, including studies of metabolism, nutrition, infection, and drug pharmacokinetics, as well as personalized medicine.  a2045-2322