The development of a functional human small intestinal epithelium model for drug absorption

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Title
The development of a functional human small intestinal epithelium model for drug absorption
Author(s)
Ohman Kwon; Kwang Bo Jung; Kyeong-Ryoon Lee; Ye Seul Son; Hana Lee; Jongjin Kim; Kwangho Kim; Seop Lee; Yoo-Kyung Song; Jaeeun Jung; Kun Hyang ParkDae Soo KimMyung Jin SonMi Ok LeeTae-Su HanHyun-Soo Cho; S J Oh; H Chung; S H Kim; Kyung-Sook ChungJanghwan KimCho-Rok JungMi-Young Son
Bibliographic Citation
Science Advances, vol. 7, no. 23, pp. eabh1586-eabh1586
Publication Year
2021
Abstract
Advanced technologies are required for generating human intestinal epithelial cells (hIECs) harboring cellular diversity and functionalities to predict oral drug absorption in humans and study normal intestinal epithelial physiology. We developed a reproducible two-step protocol to induce human pluripotent stem cells to differentiate into highly expandable hIEC progenitors and a functional hIEC monolayer exhibiting intestinal molecular features, cell type diversity, and high activities of intestinal transporters and metabolic enzymes such as cytochrome P450 3A4 (CYP3A4). Functional hIECs are more suitable for predicting compounds metabolized by CYP3A4 and absorbed in the intestine than Caco-2 cells. This system is a step toward the transition from three-dimensional (3D) intestinal organoids to 2D hIEC monolayers without compromising cellular diversity and function. A physiologically relevant hIEC model offers a novel platform for creating patient-specific assays and support translational applications, thereby bridging the gap between 3D and 2D culture models of the intestine.
ISSN
2375-2548
Publisher
Amer Assoc Advancement Science
DOI
http://dx.doi.org/10.1126/sciadv.abh1586
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
Division of Bio Technology Innovation > Core Facility Management Center > 1. Journal Articles
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
Division of Research on National Challenges > 1. Journal Articles
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