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Efficient Generation of Small Intestinal Epithelial-like Cells from Human iPSCs for Drug Absorption and Metabolism Studies.
- Source :
-
Stem cell reports [Stem Cell Reports] 2018 Dec 11; Vol. 11 (6), pp. 1539-1550. Date of Electronic Publication: 2018 Nov 21. - Publication Year :
- 2018
-
Abstract
- The small intestine plays an important role in the absorption and metabolism of oral drugs. In the current evaluation system, it is difficult to predict the precise absorption and metabolism of oral drugs. In this study, we generated small intestinal epithelial-like cells from human induced pluripotent stem cells (hiPS-SIECs), which could be applied to drug absorption and metabolism studies. The small intestinal epithelial-like cells were efficiently generated from human induced pluripotent stem cell by treatment with WNT3A, R-spondin 3, Noggin, EGF, IGF-1, SB202190, and dexamethasone. The gene expression levels of small intestinal epithelial cell (SIEC) markers were similar between the hiPS-SIECs and human adult small intestine. Importantly, the gene expression levels of colonic epithelial cell markers in the hiPS-SIECs were much lower than those in human adult colon. The hiPS-SIECs generated by our protocol exerted various SIEC functions. In conclusion, the hiPS-SIECs can be utilized for evaluation of drug absorption and metabolism.<br /> (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Biomarkers metabolism
Caco-2 Cells
Carrier Proteins pharmacology
Cell Differentiation drug effects
Dexamethasone pharmacology
Epidermal Growth Factor pharmacology
Epithelial Cells drug effects
Gene Expression Regulation drug effects
Heterocyclic Compounds, 3-Ring pharmacology
Humans
Imidazoles pharmacology
Induced Pluripotent Stem Cells drug effects
Induced Pluripotent Stem Cells metabolism
Insulin-Like Growth Factor I pharmacology
Maleimides pharmacology
Mice
Pyridines pharmacology
Thrombospondins pharmacology
Wnt3A Protein pharmacology
Epithelial Cells metabolism
Induced Pluripotent Stem Cells cytology
Intestinal Absorption drug effects
Intestine, Small cytology
Pharmaceutical Preparations metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2213-6711
- Volume :
- 11
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Stem cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 30472010
- Full Text :
- https://doi.org/10.1016/j.stemcr.2018.10.019