Human pluripotent stem cell-derived intestinal organoids for pharmacokinetic studies
The human small intestine is essential for orally administered drugs' absorption, metabolism, and excretion. Human induced pluripotent stem cell (hiPSC)-derived intestinal epithelial cells (IECs) offer a useful model for evaluating drug candidate compounds. We previously reported a protocol to...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
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| Series: | European Journal of Cell Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171933525000147 |
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| Summary: | The human small intestine is essential for orally administered drugs' absorption, metabolism, and excretion. Human induced pluripotent stem cell (hiPSC)-derived intestinal epithelial cells (IECs) offer a useful model for evaluating drug candidate compounds. We previously reported a protocol to generate matured enterocyte-like cells that exhibit P-gp-mediated efflux and cytochrome P450 3A (CYP3A)-mediated metabolism from human iPSCs. However, under the current protocols, generating iPSC-derived intestinal enterocyte-like cells requires a multi-step differentiation procedure and is time-consuming. Recent progress in intestinal organoid (IO) study provides an understanding of the growth factors that enable the maintenance of adult stem cells. Here, we established an easily accessible protocol using a direct 3D cluster culture to derive IOs from hiPSCs (iPSC-IOs) with high self-proliferative ability. The hiPSC-IOs can be propagated for a long-term and maintained capacity to differentiate and can be cryopreserved. Upon seeding on a two-dimensional monolayer, hiPSC-IOs gave rise to the intestinal epithelial cells (IECs) containing mature cell types of the intestine. The hiPSC-IOs-derived IECs contain enterocytes that show CYP metabolizing enzyme and transporter activities and can be used for pharmacokinetic studies. |
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| ISSN: | 0171-9335 |