从人诱导多能干细胞中高效生成小肠上皮样细胞用于药物吸收和代谢研究。

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

机构信息

Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.

Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan; Laboratory of Hepatocyte Regulation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Laboratory of Biochemistry and Molecular Biology, School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.

出版信息

Stem Cell Reports. 2018 Dec 11;11(6):1539-1550. doi: 10.1016/j.stemcr.2018.10.019. Epub 2018 Nov 21.

DOI:10.1016/j.stemcr.2018.10.019

PMID:30472010

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6294172/

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.

摘要

小肠在口服药物的吸收和代谢中起着重要作用。在当前的评价体系中，很难预测口服药物的精确吸收和代谢。在这项研究中，我们从人诱导多能干细胞（hiPS-SIECs）中生成了小肠上皮样细胞，可用于药物吸收和代谢研究。通过 WNT3A、R-spondin 3、Noggin、EGF、IGF-1、SB202190 和地塞米松处理，可有效地从人诱导多能干细胞中生成小肠上皮样细胞。hiPS-SIECs 中小肠上皮细胞（SIEC）标志物的基因表达水平与成人小肠相似。重要的是，hiPS-SIECs 中的结肠上皮细胞标志物的基因表达水平远低于成人结肠。我们方案中生成的 hiPS-SIECs 发挥了各种 SIEC 功能。总之，hiPS-SIECs 可用于评估药物吸收和代谢。