Prediction of drug intestinal absorption and drug-induced intestinal toxicity with the use of human crypt-derived intestinal stem cells and their differentiated cells

Q: What does this research mean for the field?

3D-cultured human crypt-derived intestinal stem cells and their differentiated cells provide an effective in vitro system for quantitatively predicting drug intestinal absorption, metabolism, and gastrointestinal toxicity, overcoming the limitations of traditional Caco-2 cell models. Novelty: ClaimNovelty.METHODOLOGICAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Kazuya Maeda

doi:10.1254/fpj.26021

August 31, 2026Folia Pharmacologica Japonica

Prediction of drug intestinal absorption and drug-induced intestinal toxicity with the use of human crypt-derived intestinal stem cells and their differentiated cells

View at Publisher

Ask AI

Bookmark

Share

Key Points

To establish and evaluate an in vitro evaluation system using human crypt-derived intestinal stem cells and their differentiated derivatives for predicting oral drug absorption and gastrointestinal toxicity.
Isolated crypts from human fresh surgical tissue and expanded intestinal stem cells in 3D Matrigel culture before differentiating them into target intestinal cell types.
Adapted models for high-throughput screening formats using commercially available frozen human intestinal specimens and 96-well vitrigel chambers.
Assessed intestinal toxicity endpoints by measuring intracellular ATP depletion in stem cells (diarrhea risk) and serotonin release from enterochromaffin-rich spheroids (nausea and vomiting risk).
Successfully modeled intestinal metabolic escape rates and PXR-mediated transcriptional induction that cannot be evaluated in conventional Caco-2 cells due to low expression levels.
Achieved favorable qualitative correlations between clinical drug-induced gastrointestinal side-effect incidence and experimental markers, including ATP reduction and serotonin secretion.

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

In vitro study demonstrates enhanced prediction of drug absorption and toxicity using human crypt stem cells, highlighting better physiological relevance over Caco-2 models.

Abstract

No abstract yet. The journal hasn't published one we can show.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Kazuya Maeda (2026) studied this question.

synapsesocial.com/papers/6a9934cf636c6408cfa7c927 https://doi.org/10.1254/fpj.26021

View at Publisher

Ask AI

Bookmark

Share

Prediction of drug intestinal absorption and drug-induced intestinal toxicity with the use of human crypt-derived intestinal stem cells and their differentiated cells

Key Points

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Prediction of drug intestinal absorption and drug-induced intestinal toxicity with the use of human crypt-derived intestinal stem cells and their differentiated cells

Key Points

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading