Duodenum Intestine-Chip for preclinical drug assessment in a human relevant model.
ATP Binding Cassette Transporter, Subfamily B
/ metabolism
Animals
Caco-2 Cells
Computational Biology
Cytochrome P-450 CYP3A
/ metabolism
Drug Evaluation, Preclinical
/ instrumentation
Drug Interactions
Duodenum
/ metabolism
Gene Expression Profiling
Gene Expression Regulation
Humans
Microvilli
Organ Culture Techniques
Organoids
/ metabolism
Permeability
Transcriptome
CYP3A4
Organs-on-Chips
cell biology
drug metabolism
drug transport
duodenum
human
organoids
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
14 01 2020
14 01 2020
Historique:
received:
12
07
2019
accepted:
18
12
2019
entrez:
15
1
2020
pubmed:
15
1
2020
medline:
15
5
2021
Statut:
epublish
Résumé
Induction of intestinal drug metabolizing enzymes can complicate the development of new drugs, owing to the potential to cause drug-drug interactions (DDIs) leading to changes in pharmacokinetics, safety and efficacy. The development of a human-relevant model of the adult intestine that accurately predicts CYP450 induction could help address this challenge as species differences preclude extrapolation from animals. Here, we combined organoids and Organs-on-Chips technology to create a human Duodenum Intestine-Chip that emulates intestinal tissue architecture and functions, that are relevant for the study of drug transport, metabolism, and DDI. Duodenum Intestine-Chip demonstrates the polarized cell architecture, intestinal barrier function, presence of specialized cell subpopulations, and
Identifiants
pubmed: 31933478
doi: 10.7554/eLife.50135
pii: 50135
pmc: PMC6959988
doi:
pii:
Substances chimiques
ABCB1 protein, human
0
ATP Binding Cassette Transporter, Subfamily B
0
Cytochrome P-450 CYP3A
EC 1.14.14.1
CYP3A4 protein, human
EC 1.14.14.55
Banques de données
GEO
['GSE135196']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK089502
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK116352
Pays : United States
Organisme : NIDDK NIH HHS
ID : R24 DK099803
Pays : United States
Informations de copyright
© 2020, Kasendra et al.
Déclaration de conflit d'intérêts
MK, RL, DM, GK, CL, JS, AA, JO, KJ, GH, KK is an employee and shareholder of Emulate, JY, LS, MD No competing interests declared
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