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Inflammation Research

, Volume 67, Issue 11–12, pp 975–984 | Cite as

Using human iPS cell-derived enterocytes as novel in vitro model for the evaluation of human intestinal mucosal damage

  • Satoshi Kondo
  • Shota Mizuno
  • Tadahiro Hashita
  • Takahiro Iwao
  • Tamihide Matsunaga
Original Research Paper
  • 145 Downloads

Abstract

Objective and design

The primary component in gut mucus is mucin 2 (MUC2) secreted by goblet cells. Fluctuations in MUC2 expression are considered a useful indicator for evaluating mucosal damage and protective effect of various agents using animal studies. However, there are few in vitro studies evaluating mucosal damage using MUC2 as the indicator. Hence, we attempted to establish a novel in vitro model with MUC2 as the indicator for evaluating drug-induced mucosal damage and protective effect using enterocytes derived from human iPS cells.

Methods

Compounds were added into enterocytes derived from human iPS cells, and MUC2 mRNA and protein expression levels were evaluated. Further, the effect of compounds on membrane permeability was investigated.

Results

Nonsteroidal anti-inflammatory drugs were found to decrease MUC2 mRNA expression in enterocytes, whereas mucosal protective agents increased mRNA levels. Changes in MUC2 protein expression were consistent with those of mRNA. Additionally, our results indicated that indomethacin caused mucosal damage, affecting membrane permeability of the drug. Moreover, we observed protective effect of rebamipide against the indomethacin-induced permeability increase.

Conclusions

The developed model could facilitate evaluating drug-induced mucosal damage and protective effects of various agents and could impact drug development studies regarding pharmacological efficacy and safety.

Keywords

Human iPS cells Enterocytes Mucin 2 Nonsteroidal anti-inflammatory drugs Mucosal protective agents 

Notes

Acknowledgements

The authors are extremely grateful to Dr. Hidenori Akutsu, Dr. Yoshitaka Miyagawa, Dr. Hajime Okita, Dr. Nobutaka Kiyokawa, Dr. Masashi Toyoda, and Dr. Akihiro Umezawa for providing the human iPS cells.

Author contributions

SK, MS, TH, TI, and TM participated in research design; SK and MS conducted experiments and performed data analysis; SK, MS, TH, TI, and TM wrote or contributed to the writing of the manuscript.

Funding

This work was supported by Grant-in-Aid for Research in Nagoya City University in 2017, and Agency for Medical Research and Development (AMED) under Grant Number 17be0304203h0001.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Drug Safety Research, Nonclinical Research CenterTokushima Research Institute, Otsuka Pharmaceutical Co., Ltd.TokushimaJapan
  2. 2.Department of Clinical Pharmacy, Graduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan

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