@article{2161, author = {Wyatt E. Lanik and Cliff J. Luke and Lila S. Nolan and Qingqing Gong and Lauren C. Frazer and Jamie M. Rimer and Sarah E. Gale and Raymond Luc and Shay S. Bidani and Carrie A. Sibbald and Angela N. Lewis and Belgacem Mihi and Pranjal Agrawal and Martin Goree and Marlie Maestas and Elise Hu and David G. Peters and Misty Good}, title = {Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis–on-a-chip}, abstract = {Necrotizing 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.,}, year = {2023}, journal = {JCI Insight}, volume = {8}, pages = {e146496}, month = {2023}, issn = {2379-3708}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243823/}, doi = {10.1172/jci.insight.146496}, }