Generation of Enterocyte-Like Cells with Pharmacokinetic Functions from Human Induced Pluripotent Stem Cells Using Small-Molecule Compounds

• DOI: 10.1124/dmd.114.062604
• Publication Date: 2015-02-04T04:35:25Z
• Authors: Takahiro Iwao; Nao Kodama; Yuki Kondo; Tomoki Kabeya; Katsunori Nakamura; Takashi Horikawa; Takuro Niwa; Kouichi Kurose; Tamihide Matsunaga
• Keywords: Enterocyte

The small intestine plays an important role in all aspects of pharmacokinetics, but there is no system for the comprehensive evaluation small-intestinal including drug metabolism and absorption. In this study, we aimed to construct intestinal pharmacokinetics generate pharmacokinetically functional enterocytes from human induced pluripotent stem cells. Using activin A fibroblast growth factor 2, differentiated these cells into cell–like cells, resulting were a medium containing epidermal small-molecule compounds. expressed marker genes transporters. expression sucrase-isomaltase, intestine-specific marker, was markedly increased by exhibited activities drug-metabolizing enzymes enterocytes, CYP1A1/2, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5, UGT, sulfotransferase. Fluorescence-labeled dipeptide uptake observed inhibited ibuprofen, inhibitor oligopeptide transporter solute carrier 15A1/PEPT1. CYP3A4 mRNA level compounds addition 1<i>α</i>,25-dihydroxyvitamin D₃. CYP3A4/5 activity also D₃ presence All results show that have generated enterocyte-like pharmacokinetic functions, identified are effective promoting differentiation gain functions. Our would be useful material developing novel predict pharmacokinetics.