TY - JOUR
AU - Wyatt E. Lanik
AU - Cliff J. Luke
AU - Lila S. Nolan
AU - Qingqing Gong
AU - Lauren C. Frazer
AU - Jamie M. Rimer
AU - Sarah E. Gale
AU - Raymond Luc
AU - Shay S. Bidani
AU - Carrie A. Sibbald
AU - Angela N. Lewis
AU - Belgacem Mihi
AU - Pranjal Agrawal
AU - Martin Goree
AU - Marlie Maestas
AU - Elise Hu
AU - David G. Peters
AU - Misty Good
AB - 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.,
BT - JCI Insight
DA - 2023
DO - 10.1172/jci.insight.146496
IS - 8
N2 - 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.,
PY - 2023
EP - e146496
T2 - JCI Insight
TI - Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis–on-a-chip
UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243823/
VL - 8
Y2 - 2023-09-15
SN - 2379-3708
ER -