Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis-on-a-chip

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

doi:10.1172/jci.insight.146496

Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis-on-a-chip

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

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English
Article number	e146496
Journal	JCI Insight
Volume	8
Issue number	8
DOIs	https://doi.org/10.1172/jci.insight.146496
State	Published - 2023

Access to Document

10.1172/jci.insight.146496

Cite this

Lanik, W. E., Luke, C. J., Nolan, L. S., Gong, Q., Frazer, L. C., Rimer, J. M., Gale, S. E., Luc, R., Bidani, S. S., Sibbald, C. A., Lewis, A. N., Mihi, B., Agrawal, P., Goree, M., Maestas, M., Hu, E., Peters, D. G., & Good, M. (2023). Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis-on-a-chip. JCI Insight, 8(8), Article e146496. https://doi.org/10.1172/jci.insight.146496

@article{ece5eb86101d43529bfddb3bc8aac771,

title = "Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis-on-a-chip",

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.",

author = "Lanik, {Wyatt E.} and Luke, {Cliff J.} and Nolan, {Lila S.} and Qingqing Gong and Frazer, {Lauren C.} and Rimer, {Jamie M.} and Gale, {Sarah E.} and Raymond Luc and Bidani, {Shay S.} and Sibbald, {Carrie A.} and Lewis, {Angela N.} and Belgacem Mihi and Pranjal Agrawal and Martin Goree and Marlie Maestas and Elise Hu and Peters, {David G.} and Misty Good",

note = "Publisher Copyright: {\textcopyright} 2023, Lanik et al.",

year = "2023",

doi = "10.1172/jci.insight.146496",

language = "English",

volume = "8",

journal = "JCI Insight",

issn = "2379-3708",

number = "8",

}

Lanik, WE, Luke, CJ , Nolan, LS, Gong, Q, Frazer, LC, Rimer, JM, Gale, SE, Luc, R, Bidani, SS, Sibbald, CA, Lewis, AN, Mihi, B, Agrawal, P, Goree, M, Maestas, M, Hu, E, Peters, DG & Good, M 2023, 'Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis-on-a-chip', JCI Insight, vol. 8, no. 8, e146496. https://doi.org/10.1172/jci.insight.146496

TY - JOUR

T1 - Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis-on-a-chip

AU - Lanik, Wyatt E.

AU - Luke, Cliff J.

AU - Nolan, Lila S.

AU - Gong, Qingqing

AU - Frazer, Lauren C.

AU - Rimer, Jamie M.

AU - Gale, Sarah E.

AU - Luc, Raymond

AU - Bidani, Shay S.

AU - Sibbald, Carrie A.

AU - Lewis, Angela N.

AU - Mihi, Belgacem

AU - Agrawal, Pranjal

AU - Goree, Martin

AU - Maestas, Marlie

AU - Hu, Elise

AU - Peters, David G.

AU - Good, Misty

PY - 2023

Y1 - 2023

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85153551275&partnerID=8YFLogxK

U2 - 10.1172/jci.insight.146496

DO - 10.1172/jci.insight.146496

M3 - Article

C2 - 36881475

AN - SCOPUS:85153551275

SN - 2379-3708

VL - 8

JO - JCI Insight

JF - JCI Insight

IS - 8

M1 - e146496

ER -

Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis-on-a-chip

Abstract

Access to Document

Other files and links

Fingerprint

Cite this