Efficient Generation of Cynomolgus Monkey Induced Pluripotent Stem Cell-Derived Intestinal Organoids with Pharmacokinetic Functions
-
- Daichi Onozato
- Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
-
- Misaki Yamashita
- Faculty of Pharmaceutical Sciences, Educational Research Center for Clinical Pharmacy, Nagoya City University, Nagoya, Japan.
-
- Ryosuke Fukuyama
- Faculty of Pharmaceutical Sciences, Educational Research Center for Clinical Pharmacy, Nagoya City University, Nagoya, Japan.
-
- Takumi Akagawa
- Faculty of Pharmaceutical Sciences, Educational Research Center for Clinical Pharmacy, Nagoya City University, Nagoya, Japan.
-
- Yuriko Kida
- Faculty of Pharmaceutical Sciences, Educational Research Center for Clinical Pharmacy, Nagoya City University, Nagoya, Japan.
-
- Akiko Koeda
- Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
-
- Tadahiro Hashita
- Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
-
- Takahiro Iwao
- Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
-
- Tamihide Matsunaga
- Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
この論文をさがす
説明
In preclinical studies, the cynomolgus monkey (CM) model is frequently used to predict the pharmacokinetics of drugs in the human small intestine, because of its evolutionary closeness to humans. Intestinal organoids that mimic the intestinal tissue have attracted attention in regenerative medicine and drug development. In this study, we generated intestinal organoids from CM induced pluripotent stem (CMiPS) cells and analyzed their pharmacokinetic functions. CMiPS cells were induced into the hindgut; then, the cells were seeded on microfabricated culture vessel plates to form spheroids. The resulting floating spheroids were differentiated into intestinal organoids in a medium containing small-molecule compounds. The mRNA expression of intestinal markers and pharmacokinetic-related genes was markedly increased in the presence of small-molecule compounds. The organoids possessed a polarized epithelium and contained various cells constituting small intestinal tissues. The intestinal organoids formed functional tight junctions and expressed drug transporter proteins. In addition, in the organoids generated, cytochrome P450 3A8 (CYP3A8) activity was inhibited by the specific inhibitor ketoconazole and was induced by rifampicin. Therefore, in the present work, we successfully generated intestinal organoids, with pharmacokinetic functions, from CMiPS cells using small-molecule compounds.
収録刊行物
-
- Stem Cells and Development
-
Stem Cells and Development 27 (15), 1033-1045, 2018-08
Mary Ann Liebert Inc
