Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis–on-a-chip
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 neo...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2023-04-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.146496 |
| _version_ | 1827767959556194304 |
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| author | Wyatt E. Lanik Cliff J. Luke Lila S. Nolan Qingqing Gong Lauren C. Frazer Jamie M. Rimer Sarah E. Gale Raymond Luc Shay S. Bidani Carrie A. Sibbald Angela N. Lewis Belgacem Mihi Pranjal Agrawal Martin Goree Marlie Maestas Elise Hu David G. Peters Misty Good |
| author_facet | Wyatt E. Lanik Cliff J. Luke Lila S. Nolan Qingqing Gong Lauren C. Frazer Jamie M. Rimer Sarah E. Gale Raymond Luc Shay S. Bidani Carrie A. Sibbald Angela N. Lewis Belgacem Mihi Pranjal Agrawal Martin Goree Marlie Maestas Elise Hu David G. Peters Misty Good |
| author_sort | Wyatt E. Lanik |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T12:06:44Z |
| format | Article |
| id | doaj.art-8016507d4d3a4af39d3df3252b403b98 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:06:44Z |
| publishDate | 2023-04-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-8016507d4d3a4af39d3df3252b403b982023-11-07T16:25:31ZengAmerican Society for Clinical investigationJCI Insight2379-37082023-04-0188Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis–on-a-chipWyatt E. LanikCliff J. LukeLila S. NolanQingqing GongLauren C. FrazerJamie M. RimerSarah E. GaleRaymond LucShay S. BidaniCarrie A. SibbaldAngela N. LewisBelgacem MihiPranjal AgrawalMartin GoreeMarlie MaestasElise HuDavid G. PetersMisty GoodNecrotizing 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.https://doi.org/10.1172/jci.insight.146496Cell biologyInflammation |
| spellingShingle | Wyatt E. Lanik Cliff J. Luke Lila S. Nolan Qingqing Gong Lauren C. Frazer Jamie M. Rimer Sarah E. Gale Raymond Luc Shay S. Bidani Carrie A. Sibbald Angela N. Lewis Belgacem Mihi Pranjal Agrawal Martin Goree Marlie Maestas Elise Hu David G. Peters Misty Good Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis–on-a-chip JCI Insight Cell biology Inflammation |
| title | Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis–on-a-chip |
| title_full | Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis–on-a-chip |
| title_fullStr | Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis–on-a-chip |
| title_full_unstemmed | Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis–on-a-chip |
| title_short | Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis–on-a-chip |
| title_sort | microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis on a chip |
| topic | Cell biology Inflammation |
| url | https://doi.org/10.1172/jci.insight.146496 |
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