論文 - 詳細
| RRC ID | 81391 |
|---|---|
| 著者 | Takahashi Y, Noguchi M, Inoue Y, Sato S, Shimizu M, Kojima H, Okabe T, Kiyono H, Yamauchi Y, Sato R. |
| タイトル | Organoid-derived intestinal epithelial cells are a suitable model for preclinical toxicology and pharmacokinetic studies. |
| ジャーナル | iScience |
| Abstract |
Intestinal organoids are physiologically relevant tools used for cellular models. However, the suitability of organoids to examine biological functions over existing established cell lines lacks sufficient evidence. Cytochrome P450 3A4 (CYP3A4) induction by pregnane X receptor ligands, glucose uptake via sodium/glucose cotransporter 1, and microsomal triglyceride transfer protein-dependent ApoB-48 secretion, which are critical for human intestinal metabolism, were observed in organoid-derived two-dimensional cells but little in Caco-2 cells. CYP3A4 induction evaluation involved a simplified method of establishing organoids that constitutively expressed a reporter gene. Compound screening identified several anticancer drugs with selective activities toward Caco-2 cells, highlighting their characteristics as cancer cells. Another compound screening revealed a decline in N-(4-hydroxyphenyl)retinamide cytotoxicity upon rifampicin treatment in organoid-derived cells, under CYP3A4-induced conditions. This study shows that organoid-derived intestinal epithelial cells (IECs) possess similar physiological properties as intestinal epithelium and can serve as tools for enhancing the prediction of biological activity in humans. |
| 巻・号 | 25(7) |
| ページ | 104542 |
| 公開日 | 2022-7-15 |
| DOI | 10.1016/j.isci.2022.104542 |
| PII | S2589-0042(22)00814-8 |
| PMID | 35754737 |
| PMC | PMC9218437 |
| IF | 4.447 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| 遺伝子材料 | CS-UbC-hSox2-IRES2-Venus (RDB12915) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394) |