Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis–on-a-chip
Year: 2023
Type: article
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.
Source: JCI Insight
Language: English
Topic: Infant Nutrition and Health
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Funders: Thrasher Research Fund, Children's Discovery Institute, Children's Hospital Foundation, Alvin J. Siteman Cancer Center, National Institutes of Health, Gillings School of Public Health, University of North Carolina at Chapel Hill, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1114310655, Inhibitors of Intestinal Epithelial Cell Lysosomal-Mediated Necrosis, G299873027, Neonatal gut-on-a-chip platform for high content drug testing and precision medicine, Non-invasive analysis of methylated cell free DNA in necrotizing enterocolitis, Modulation of the Intestinal Immune Response in Necrotizing Enterocolitis, G6321272096, G8242737674, G9000319192, Cancer Center Support Grant, Training of the Pediatric Physician-Scientist
OpenAlex ID: W4323348532