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Usefulness of Human Jejunal Spheroid–Derived Differentiated Intestinal Epithelial Cells for the Prediction of Intestinal Drug Absorption in Humans by Kazuyoshi Michiba; Kazuya Maeda; Osamu Shimomura; Yoshihiro Miyazaki; Shinji Hashimoto; Tatsuya Oda; Hiroyuki Kusuhara is a Medicine article available to read on EtoBox.
What is Usefulness of Human Jejunal Spheroid–Derived Differentiated Intestinal Epithelial Cells for the Prediction of Intestinal Drug Absorption in Humans about?
This study aimed to demonstrate the usefulness of human jejunal spheroid-derived differentiated intestinal epithelial cells as a novel in vitro model for clarifying the impact of intestinal drug-metabolizing enzymes and transporters on the intestinal absorption of substrate drugs in humans. Three-dimensional human intestinal spheroids were successfully established from surgical human jejunal specimens and expanded for a long period using L-WRN-conditioned medium, which contains Wnt3a, R-spondin 3, and noggin. The mRNA expression levels of intestinal pharmacokinetics-related genes in the human jejunal spheroid-derived differentiated intestinal epithelial cells were drastically increased over a 5-day period after seeding compared with those in human jejunal spheroids and were approximately the same as those in human jejunal tissue over a culture period of at least 13 days. Activities of typical drug-metabolizing enzymes [cytochrome P450 (CYP) 3A, CYP2C9, uridine 5'-diphospho-glucuronosyltransferase 1A, and carboxylesterase 2] and uptake/efflux transporters [peptide transporter 1/solute carrier ], P-glycoprotein, and breast cancer resistance protein) in the differentiated cells were c
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It is typically read by researchers, students, and practitioners in Medicine.
- Author
- Kazuyoshi Michiba; Kazuya Maeda; Osamu Shimomura; Yoshihiro Miyazaki; Shinji Hashimoto; Tatsuya Oda; Hiroyuki Kusuhara
- Publisher
- American Society for Pharmacology & Experimental Therapeutics (ASPET)
- Published
- 2022
- Language
- EN
- Field
- Medicine (Life Sciences)