Microfluidic Model of Necrotizing Enterocolitis Incorporating Human Neonatal Intestinal Enteroids and a Dysbiotic Microbiome.

Autor: Frazer LC; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina at Chapel Hill., Yamaguchi Y; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina at Chapel Hill., Jania CM; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina at Chapel Hill., Lanik WE; University of Nebraska College of Medicine., Gong Q; Department of Surgery, Washington University School of Medicine., Singh DK; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina at Chapel Hill., Mackay S; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina at Chapel Hill., Akopyants NS; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina at Chapel Hill., Good M; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina at Chapel Hill; mistygood@unc.edu.
Jazyk: angličtina
Zdroj: Journal of visualized experiments : JoVE [J Vis Exp] 2023 Jul 28 (197). Date of Electronic Publication: 2023 Jul 28.
DOI: 10.3791/65605
Abstrakt: Necrotizing enterocolitis (NEC) is a severe and potentially fatal intestinal disease that has been difficult to study due to its complex pathogenesis, which remains incompletely understood. The pathophysiology of NEC includes disruption of intestinal tight junctions, increased gut barrier permeability, epithelial cell death, microbial dysbiosis, and dysregulated inflammation. Traditional tools to study NEC include animal models, cell lines, and human or mouse intestinal organoids. While studies using those model systems have improved the field's understanding of disease pathophysiology, their ability to recapitulate the complexity of human NEC is limited. An improved in vitro model of NEC using microfluidic technology, named NEC-on-a-chip, has now been developed. The NEC-on-a-chip model consists of a microfluidic device seeded with intestinal enteroids derived from a preterm neonate, co-cultured with human endothelial cells and the microbiome from an infant with severe NEC. This model is a valuable tool for mechanistic studies into the pathophysiology of NEC and a new resource for drug discovery testing for neonatal intestinal diseases. In this manuscript, a detailed description of the NEC-on-a-chip model will be provided.
Databáze: MEDLINE