Efficient Generation of Small Intestinal Epithelial-like Cells from Human iPSCs for Drug Absorption and Metabolism Studies

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 pluripot...

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Autores principales: Negoro, Ryosuke, Takayama, Kazuo, Kawai, Kanae, Harada, Kazuo, Sakurai, Fuminori, Hirata, Kazumasa, Mizuguchi, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Resource
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294172/
https://www.ncbi.nlm.nih.gov/pubmed/30472010
http://dx.doi.org/10.1016/j.stemcr.2018.10.019
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author Negoro, Ryosuke
Takayama, Kazuo
Kawai, Kanae
Harada, Kazuo
Sakurai, Fuminori
Hirata, Kazumasa
Mizuguchi, Hiroyuki
author_facet Negoro, Ryosuke
Takayama, Kazuo
Kawai, Kanae
Harada, Kazuo
Sakurai, Fuminori
Hirata, Kazumasa
Mizuguchi, Hiroyuki
author_sort Negoro, Ryosuke
collection PubMed
description 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.
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spelling pubmed-62941722018-12-21 Efficient Generation of Small Intestinal Epithelial-like Cells from Human iPSCs for Drug Absorption and Metabolism Studies Negoro, Ryosuke Takayama, Kazuo Kawai, Kanae Harada, Kazuo Sakurai, Fuminori Hirata, Kazumasa Mizuguchi, Hiroyuki Stem Cell Reports Resource 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. Elsevier 2018-11-21 /pmc/articles/PMC6294172/ /pubmed/30472010 http://dx.doi.org/10.1016/j.stemcr.2018.10.019 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Resource
Negoro, Ryosuke
Takayama, Kazuo
Kawai, Kanae
Harada, Kazuo
Sakurai, Fuminori
Hirata, Kazumasa
Mizuguchi, Hiroyuki
Efficient Generation of Small Intestinal Epithelial-like Cells from Human iPSCs for Drug Absorption and Metabolism Studies
title Efficient Generation of Small Intestinal Epithelial-like Cells from Human iPSCs for Drug Absorption and Metabolism Studies
title_full Efficient Generation of Small Intestinal Epithelial-like Cells from Human iPSCs for Drug Absorption and Metabolism Studies
title_fullStr Efficient Generation of Small Intestinal Epithelial-like Cells from Human iPSCs for Drug Absorption and Metabolism Studies
title_full_unstemmed Efficient Generation of Small Intestinal Epithelial-like Cells from Human iPSCs for Drug Absorption and Metabolism Studies
title_short Efficient Generation of Small Intestinal Epithelial-like Cells from Human iPSCs for Drug Absorption and Metabolism Studies
title_sort efficient generation of small intestinal epithelial-like cells from human ipscs for drug absorption and metabolism studies
topic Resource
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294172/
https://www.ncbi.nlm.nih.gov/pubmed/30472010
http://dx.doi.org/10.1016/j.stemcr.2018.10.019
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