Generation of Human iPSC-Derived Intestinal Epithelial Cell Monolayers by CDX2 Transduction.
CDX2 Transcription Factor
/ genetics
Caco-2 Cells
Cell Culture Techniques
Cell Differentiation
Cells, Cultured
Cytochrome P-450 CYP3A
/ metabolism
Drug Interactions
Epithelial Cells
/ cytology
Food-Drug Interactions
Fruit and Vegetable Juices
Humans
Induced Pluripotent Stem Cells
/ cytology
Intestinal Absorption
Intestines
/ cytology
Rifampin
/ pharmacokinetics
Transduction, Genetic
/ methods
Adenovirus
CYP3A4
Differentiation
Intestinal First-Pass Effect
Journal
Cellular and molecular gastroenterology and hepatology
ISSN: 2352-345X
Titre abrégé: Cell Mol Gastroenterol Hepatol
Pays: United States
ID NLM: 101648302
Informations de publication
Date de publication:
2019
2019
Historique:
received:
23
09
2018
revised:
11
06
2019
accepted:
12
06
2019
pubmed:
23
6
2019
medline:
21
7
2020
entrez:
23
6
2019
Statut:
ppublish
Résumé
To develop an effective and safe orally administered drug, it is important to predict its intestinal absorption rate, intestinal first-pass effect, and drug-drug interactions of orally administered drugs. However, there is no existing model to comprehensively predict the intestinal pharmacokinetics and drug-response of orally administered drugs. In this study, we attempted to generate homogenous and functional intestinal epithelial cells from human induced pluripotent stem (iPS) cells for pharmaceutical research. We generated almost-homogenous Villin- and zonula occludens-1 (ZO1)-positive intestinal epithelial cells by caudal-related homeobox transcription factor 2 (CDX2) transduction into human iPS cell-derived intestinal progenitor cells. The drug absorption rates in human iPS cell-derived intestinal epithelial cell monolayers (iPS-IECM) were highly correlated with those in humans (R Taking these results together, we succeeded in generating the human iPS-IECM that can be applied to various intestinal pharmacokinetics and drug-response tests of orally administered drugs.
Sections du résumé
BACKGROUND & AIMS
To develop an effective and safe orally administered drug, it is important to predict its intestinal absorption rate, intestinal first-pass effect, and drug-drug interactions of orally administered drugs. However, there is no existing model to comprehensively predict the intestinal pharmacokinetics and drug-response of orally administered drugs. In this study, we attempted to generate homogenous and functional intestinal epithelial cells from human induced pluripotent stem (iPS) cells for pharmaceutical research.
METHODS
We generated almost-homogenous Villin- and zonula occludens-1 (ZO1)-positive intestinal epithelial cells by caudal-related homeobox transcription factor 2 (CDX2) transduction into human iPS cell-derived intestinal progenitor cells.
RESULTS
The drug absorption rates in human iPS cell-derived intestinal epithelial cell monolayers (iPS-IECM) were highly correlated with those in humans (R
CONCLUSION
Taking these results together, we succeeded in generating the human iPS-IECM that can be applied to various intestinal pharmacokinetics and drug-response tests of orally administered drugs.
Identifiants
pubmed: 31228606
pii: S2352-345X(19)30082-7
doi: 10.1016/j.jcmgh.2019.06.004
pmc: PMC6722387
pii:
doi:
Substances chimiques
CDX2 Transcription Factor
0
CDX2 protein, human
0
Cytochrome P-450 CYP3A
EC 1.14.14.1
CYP3A4 protein, human
EC 1.14.14.55
Rifampin
VJT6J7R4TR
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
513-526Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.