02228nas a2200349 4500000000100000008004100001260000900042100001900051700001800070700001800088700001800106700002100124700001900145700001800164700001600182700001900198700002200217700002000239700001800259700002000277700001700297700001900314700001300333700002000346700001500366245011000381856005900491300001200550490000600562520129600568022001401864 2023 d c20231 aWyatt E. Lanik1 aCliff J. Luke1 aLila S. Nolan1 aQingqing Gong1 aLauren C. Frazer1 aJamie M. Rimer1 aSarah E. Gale1 aRaymond Luc1 aShay S. Bidani1 aCarrie A. Sibbald1 aAngela N. Lewis1 aBelgacem Mihi1 aPranjal Agrawal1 aMartin Goree1 aMarlie Maestas1 aElise Hu1 aDavid G. Peters1 aMisty Good00aMicrofluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis–on-a-chip uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243823/ ae1464960 v83 aNecrotizing enterocolitis (NEC) is a deadly gastrointestinal disease of premature infants that is associated with an exaggerated inflammatory response, dysbiosis of the gut microbiome, decreased epithelial cell proliferation, and gut barrier disruption. We describe an in vitro model of the human neonatal small intestinal epithelium (Neonatal-Intestine-on-a-Chip) that mimics key features of intestinal physiology. This model utilizes intestinal enteroids grown from surgically harvested intestinal tissue from premature infants and cocultured with human intestinal microvascular endothelial cells within a microfluidic device. We used our Neonatal-Intestine-on-a-Chip to recapitulate NEC pathophysiology by adding infant-derived microbiota. This model, named NEC-on-a-Chip, simulates the predominant features of NEC, including significant upregulation of proinflammatory cytokines, decreased intestinal epithelial cell markers, reduced epithelial proliferation, and disrupted epithelial barrier integrity. NEC-on-a-Chip provides an improved preclinical model of NEC that facilitates comprehensive analysis of the pathophysiology of NEC using precious clinical samples. This model is an advance toward a personalized medicine approach to test new therapeutics for this devastating disease., a2379-3708