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Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids

2018· article· en· 732 citations· W2794369551 on OpenAlex· 10.1038/s41598-018-21201-7

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Abstract

Here 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.

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The record

Venue
Scientific Reports
Topic
3D Printing in Biomedical Research
Field
Engineering
Canadian institutions
Funders
Intellectual and Developmental Disabilities Research CenterU.S. Food and Drug AdministrationNational Institutes of HealthDefense Advanced Research Projects AgencyRagon Institute of MGH, MIT and HarvardNorth American Society for Pediatric Gastroenterology, Hepatology and NutritionEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentHansjörg Wyss Institute for Biologically Inspired Engineering, Harvard UniversityHarvard UniversityHarvard Digestive Diseases Center, Harvard UniversityHamilton Health Sciences FoundationNational Institute of Diabetes and Digestive and Kidney DiseasesBill and Melinda Gates Foundation
Keywords
OrganoidSmall intestineLumen (anatomy)Cell biologyIntestinal epitheliumBiologyCryptIntestinal mucosaEpitheliumChemistryBiochemistryInternal medicineMedicineEndocrinology
Has abstract in OpenAlex
yes