Establishment of MDR1-knockout human induced pluripotent stem cell line.

ATP Binding Cassette Transporter, Subfamily B / deficiency Cell Differentiation Gene Editing Humans Induced Pluripotent Stem Cells / cytology
ABCB1 CRISPR-Cas9 Genome editing Hepatocytes MDR1 P-gp Transporter iPS cell

Journal

Drug metabolism and pharmacokinetics
ISSN: 1880-0920
Titre abrégé: Drug Metab Pharmacokinet
Pays: England
ID NLM: 101164773

Informations de publication

Date de publication:
Jun 2020
Historique:
received: 10 11 2019
revised: 28 01 2020
accepted: 31 01 2020
pubmed: 19 4 2020
medline: 23 12 2020
entrez: 19 4 2020
Statut: ppublish

Résumé

Multiple drug resistance 1 (MDR1) is highly expressed in various organs, including the liver, small intestine, and blood-brain barrier (BBB). Because MDR1 plays important roles in the excretion of many drugs, it is necessary to evaluate whether drug candidates are potential substrates of MDR1. Recently, many researchers have shown that human induced pluripotent stem (iPS) cell-derived differentiated cells such as hepatocytes and enterocytes can be applied for pharmacokinetic testing. Here, we attempted to generate MDR1-knockout (KO) iPS cell lines using genome editing technology. The correctly targeted human iPS cell lines were successfully obtained. The expression levels of pluripotent markers in human iPS cells were not changed by MDR1 knockout. The gene expression levels of hepatic markers in MDR1-KO iPS-derived hepatocyte-like cells were higher than those in undifferentiated MDR1-KO iPS cells, suggesting that MDR1-KO iPS cells have hepatic differentiation capacity. In addition, MDR1 expression levels were hardly detected in MDR1-KO iPS cell-derived hepatocyte-like cells. We thus succeeded in establishing MDR1-KO iPS cell lines that could be utilized for pharmacokinetic testing.

Identifiants

DOI: 10.1016/j.dmpk.2020.01.009 PMID: 32303458
pubmed: 32303458
pii: S1347-4367(20)30014-8
doi: 10.1016/j.dmpk.2020.01.009
pii:
doi:

Substances chimiques

ABCB1 protein, human 0
ATP Binding Cassette Transporter, Subfamily B 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

288-296

Informations de copyright

Copyright © 2020 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare no conflict of interest.

Auteurs

Ryosuke Negoro (R)

Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan.

Kanae Kawai (K)

Laboratory of Biochemistry and Molecular Biology, School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan.

Moe Ichikawa (M)

Laboratory of Biochemistry and Molecular Biology, School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan.

Sayaka Deguchi (S)

Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan; Laboratory of Hepatocyte Regulation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, 567-0085, Japan.

Kazuo Takayama (K)

Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan; Laboratory of Biochemistry and Molecular Biology, School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan; Laboratory of Hepatocyte Regulation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, 567-0085, Japan; PRESTO, Japan Science and Technology Agency, Saitama, 332-0012, Japan. Electronic address: takayama@phs.osaka-u.ac.jp.

Hiroyuki Mizuguchi (H)

Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan; Laboratory of Biochemistry and Molecular Biology, School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan; Laboratory of Hepatocyte Regulation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, 567-0085, Japan; Global Center for Medical Engineering and Informatics, Osaka University, Osaka, 565-0871, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, 565-0871, Japan. Electronic address: mizuguch@phs.osaka-u.ac.jp.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs d'anions › Transporteurs d'anions organiques › Transporteurs d'anions organiques ATP-dépendants › Sous-famille B de transporteurs à cassette liant l'ATP › Establishment of MDR1-knockout human induced...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Establishment of MDR1-knockout human induced...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Génie génétique › Édition de gène › Establishment of MDR1-knockout human induced...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Establishment of MDR1-knockout human induced...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches pluripotentes › Cellules souches pluripotentes induites › Establishment of MDR1-knockout human induced...