Microfluidic Device Facilitates Novel In Vitro Modeling of Human Neonatal Necrotizing Enterocolitis-on-a-Chip

Lanik, W. E.; Luke, C. J.; Nolan, L. S.; Gong, Q.; Rimer, J. M.; Gale, S. E.; Luc, R.; Bidani, S. S.; Sibald, C. A.; Lewis, A. N.; Mihi, B.; Agrawal, P.; Goree, M.; Maestas, M.; Hu, E.; Peters, D. G.; Good, M.

doi:10.1101/2020.11.29.402735

bioRxiv · 10.1101/2020.11.29.402735

Microfluidic Device Facilitates Novel In Vitro Modeling of Human Neonatal Necrotizing Enterocolitis-on-a-Chip

Lanik, W. E.·Luke, C. J.·Nolan, L. S.·Gong, Q.·Rimer, J. M.·Gale, S. E.·Luc, R.·Bidani, S. S.·Sibald, C. A.·Lewis, A. N.·Mihi, B.·Agrawal, P.·Goree, M.·Maestas, M.·Hu, E.·Peters, D. G.·Good, M.

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Abstract

Necrotizing enterocolitis (NEC) is a deadly gastrointestinal disease of premature infants characterized by an exaggerated inflammatory response, dysbiosis of the gut microbiome, decreased epithelial cell proliferation, and gut barrier disruption. Here, we describe a novel in vitro model of human neonatal small intestinal epithelium (Neonatal-Intestine-on-a-Chip) that mimics key features of intestinal physiology by utilizing a combination of premature infant intestinal enteroids co-cultured with human intestinal microvascular endothelial cells within a microfluidic device. We used our Neonatal-Intestine-on-a-Chip to recapitulate NEC pathophysiology in an in vitro model system of the premature gut inoculated with infant-derived microbiota. This model, also known as NEC-on-a-Chip, emulates the prominent features of NEC, demonstrating significant upregulation of pro-inflammatory cytokines, decreased intestinal epithelial cell markers, reduced epithelial proliferation and disrupted epithelial barrier integrity. NEC-on-a-Chip provides a novel preclinical model of NEC, which may be used as a personalized medicine approach to test new therapeutics for this devastating disease.

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Lanik, W. E., Luke, C. J., Nolan, L. S., Gong, Q., Rimer, J. M., Gale, S. E., Luc, R., Bidani, S. S., Sibald, C. A., Lewis, A. N., Mihi, B., Agrawal, P., Goree, M., Maestas, M., Hu, E., Peters, D. G., Good, M.. 2020-11-29. Microfluidic Device Facilitates Novel In Vitro Modeling of Human Neonatal Necrotizing Enterocolitis-on-a-Chip. https://doi.org/10.1101/2020.11.29.402735

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