title: A Novel Model of P-Glycoprotein Inhibitor Screening Using Human Small Intestinal Organoids.
abstract: P-glycoprotein (P-gp), an important efflux transporter in intestine, regulates the bioavailability of orally taken drugs. To develop an in vitro model that preferably mimics the physiological microenvironment of human intestine, we employed the three-dimensionally (3D) cultured organoids from human normal small intestinal epithelium. It was observed that the intestinal crypts could efficiently form cystic organoid structure with the extension of culture time. Furthermore, the physiological expression of ABCB1 was detected at both mRNA and protein levels in cultured organoids. Rhodamine 123 (Rh123), a typical substrate of P-gp, was actively transported across 3D organoids and accumulated in the luminal space. This transport process was also inhibited by verapamil and mitotane. In summary, the above-mentioned model based on human small intestinal 3D organoids is suitable to imitate the small intestinal epithelium and could be used as a novel in vitro model especially for P-gp inhibitor screening.
authors.affiliation: East China Normal University and Shanghai Fengxian District Central Hospital Joint Research Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Junfang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: East China Normal University and Shanghai Fengxian District Central Hospital Joint Research Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: East China Normal University and Shanghai Fengxian District Central Hospital Joint Research Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.|Shanghai Fengxian District Central Hospital, Shanghai, China.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Sun
authors.affiliation: East China Normal University and Shanghai Fengxian District Central Hospital Joint Research Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Yuanjin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: East China Normal University and Shanghai Fengxian District Central Hospital Joint Research Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Dali
authors.initials: D
authors.lastname: Li
authors.affiliation: East China Normal University and Shanghai Fengxian District Central Hospital Joint Research Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.|Shanghai Fengxian District Central Hospital, Shanghai, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: East China Normal University and Shanghai Fengxian District Central Hospital Joint Research Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.|Department of Molecular and Cellular Medicine, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: East China Normal University and Shanghai Fengxian District Central Hospital Joint Research Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors; D001682:Biological Availability; D001692:Biological Transport / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects*; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D008939:Mitotane / Q000494:pharmacology; D008954:Models, Biological; D009940:Organoids / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D020112:Rhodamine 123 / Q000493:pharmacokinetics; D046509:Tissue Culture Techniques; D014700:Verapamil / Q000494:pharmacology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D049990:Membrane Transport Modulators; D012333:RNA, Messenger; D020112:Rhodamine 123; D008939:Mitotane; D014700:Verapamil