Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 472, Issue 4, Pages 631-636Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2016.03.012
Keywords
Human iPS cells; Enterocyte-like cells; CYP3A4 induction; Nuclear receptor
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Funding
- Japan Agency for Medical Research and development (AMED) [15mk0101011h0102]
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research (K-CONNEX
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Many drugs have potential to induce the expression of drug-metabolizing enzymes, particularly cytochrome P450 3A4 (CYP3A4), in small intestinal enterocytes. Therefore, a model that can accurately evaluate drug-mediated CYP3A4 induction is urgently needed. In this study, we overlaid Matrigel on the human induced pluripotent stem cells-derived enterocyte-like cells (hiPS-ELCs) to generate the mature hiPS-ELCs that could be applied to drug-mediated CYP3A4 induction test. By overlaying Matrigel in the maturation process of enterocyte-like cells, the gene expression levels of intestinal markers (VILLIN, sucrase-isomaltase, intestine-specific homeobox, caudal type homeobox 2, and intestinal fatty acid-binding protein) were enhanced suggesting that the enterocyte-like cells were maturated by Matrigel overlay. The percentage of VILLIN-positive cells in the hiPS-ELCs found to be approximately 55.6%. To examine the CYP3A4 induction potential, the hiPS-ELCs were treated with various drugs. Treatment with dexamethasone, phenobarbital, rifampicin, or alpha,25-dihydroxyvitamin D3 resulted in 5.8-fold, 13.4-fold, 9.8 fold, or 95.0-fold induction of CYP3A4 expression relative to that in the untreated controls, respectively. These results suggest that our hiPS-ELCs would be a useful model for CYP3A4 induction test. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
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