Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective
Abstract The current in vitro or in vivo intestinal fibrosis models have many limitations. Recent advancements in the isolation and culturing of organoids has led to development of various three-dimensional (3D) intestinal disease models with in vivo physiology. In this study, we generated an organo...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Portfolio
2017-05-01
|
Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-017-02190-5 |
_version_ | 1818429672798552064 |
---|---|
author | Soojung Hahn Myeong-Ok Nam Jung Hyun Noh Dong Hyeon Lee Hyun Wook Han Duk Hwan Kim Ki Baik Hahm Sung Pyo Hong Jun-Hwan Yoo Jongman Yoo |
author_facet | Soojung Hahn Myeong-Ok Nam Jung Hyun Noh Dong Hyeon Lee Hyun Wook Han Duk Hwan Kim Ki Baik Hahm Sung Pyo Hong Jun-Hwan Yoo Jongman Yoo |
author_sort | Soojung Hahn |
collection | DOAJ |
description | Abstract The current in vitro or in vivo intestinal fibrosis models have many limitations. Recent advancements in the isolation and culturing of organoids has led to development of various three-dimensional (3D) intestinal disease models with in vivo physiology. In this study, we generated an organoid-based epithelial to mesenchymal transition (OEMT) model, which could be used as a novel intestinal fibrosis model. Intestinal epithelial organoids (IEOs) were isolated and cultured from the small intestines of normal mice. IEOs were treated with transforming growth factor- β1 (TGF-β1) or Tumor necrosis factor-α (TNF-α) to evaluate their phenotypic change. Raw 264.7 cells (macrophage) stimulated with lipopolysaccharide were co-cultured with IEOs in growth media with or without TGF-β1. TGF-β1 alone slightly induced epithelial to mesenchymal transition (EMT) in the IEOs but mainly disrupted them. Macrophage released cytokines synergistically induced mesenchymal phenotypic changes in TGF-β1 stimulated intestinal organoids. TNF-α and TGF-β1 synergistically induced proliferation of mesenchymal cells as well as EMT in the IEOs. We generated a novel OEMT model based on our finding that TNF-α and TGF-β synergistically induce type 2 EMT in IEOs. This 3D EMT model with in vivo physiology could be used to study EMT associated intestinal fibrosis. |
first_indexed | 2024-12-14T15:21:15Z |
format | Article |
id | doaj.art-ebee737219a842cf96b0be81c627d7ca |
institution | Directory Open Access Journal |
issn | 2045-2322 |
language | English |
last_indexed | 2024-12-14T15:21:15Z |
publishDate | 2017-05-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Scientific Reports |
spelling | doaj.art-ebee737219a842cf96b0be81c627d7ca2022-12-21T22:56:09ZengNature PortfolioScientific Reports2045-23222017-05-017111110.1038/s41598-017-02190-5Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspectiveSoojung Hahn0Myeong-Ok Nam1Jung Hyun Noh2Dong Hyeon Lee3Hyun Wook Han4Duk Hwan Kim5Ki Baik Hahm6Sung Pyo Hong7Jun-Hwan Yoo8Jongman Yoo9Department of Microbiology, School of Medicine, CHA UniversityDepartment of Microbiology, School of Medicine, CHA UniversityDepartment of Microbiology, School of Medicine, CHA UniversityInstitute of Basic Medical Sciences, School of Medicine, CHA UniversityInstitute of Basic Medical Sciences, School of Medicine, CHA UniversityDepartment of Gastroenterology, CHA Bundang Medical Center, CHA UniversityDepartment of Gastroenterology, CHA Bundang Medical Center, CHA UniversityDepartment of Gastroenterology, CHA Bundang Medical Center, CHA UniversityInstitute of Basic Medical Sciences, School of Medicine, CHA UniversityDepartment of Microbiology, School of Medicine, CHA UniversityAbstract The current in vitro or in vivo intestinal fibrosis models have many limitations. Recent advancements in the isolation and culturing of organoids has led to development of various three-dimensional (3D) intestinal disease models with in vivo physiology. In this study, we generated an organoid-based epithelial to mesenchymal transition (OEMT) model, which could be used as a novel intestinal fibrosis model. Intestinal epithelial organoids (IEOs) were isolated and cultured from the small intestines of normal mice. IEOs were treated with transforming growth factor- β1 (TGF-β1) or Tumor necrosis factor-α (TNF-α) to evaluate their phenotypic change. Raw 264.7 cells (macrophage) stimulated with lipopolysaccharide were co-cultured with IEOs in growth media with or without TGF-β1. TGF-β1 alone slightly induced epithelial to mesenchymal transition (EMT) in the IEOs but mainly disrupted them. Macrophage released cytokines synergistically induced mesenchymal phenotypic changes in TGF-β1 stimulated intestinal organoids. TNF-α and TGF-β1 synergistically induced proliferation of mesenchymal cells as well as EMT in the IEOs. We generated a novel OEMT model based on our finding that TNF-α and TGF-β synergistically induce type 2 EMT in IEOs. This 3D EMT model with in vivo physiology could be used to study EMT associated intestinal fibrosis.https://doi.org/10.1038/s41598-017-02190-5 |
spellingShingle | Soojung Hahn Myeong-Ok Nam Jung Hyun Noh Dong Hyeon Lee Hyun Wook Han Duk Hwan Kim Ki Baik Hahm Sung Pyo Hong Jun-Hwan Yoo Jongman Yoo Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective Scientific Reports |
title | Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective |
title_full | Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective |
title_fullStr | Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective |
title_full_unstemmed | Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective |
title_short | Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective |
title_sort | organoid based epithelial to mesenchymal transition oemt model from an intestinal fibrosis perspective |
url | https://doi.org/10.1038/s41598-017-02190-5 |
work_keys_str_mv | AT soojunghahn organoidbasedepithelialtomesenchymaltransitionoemtmodelfromanintestinalfibrosisperspective AT myeongoknam organoidbasedepithelialtomesenchymaltransitionoemtmodelfromanintestinalfibrosisperspective AT junghyunnoh organoidbasedepithelialtomesenchymaltransitionoemtmodelfromanintestinalfibrosisperspective AT donghyeonlee organoidbasedepithelialtomesenchymaltransitionoemtmodelfromanintestinalfibrosisperspective AT hyunwookhan organoidbasedepithelialtomesenchymaltransitionoemtmodelfromanintestinalfibrosisperspective AT dukhwankim organoidbasedepithelialtomesenchymaltransitionoemtmodelfromanintestinalfibrosisperspective AT kibaikhahm organoidbasedepithelialtomesenchymaltransitionoemtmodelfromanintestinalfibrosisperspective AT sungpyohong organoidbasedepithelialtomesenchymaltransitionoemtmodelfromanintestinalfibrosisperspective AT junhwanyoo organoidbasedepithelialtomesenchymaltransitionoemtmodelfromanintestinalfibrosisperspective AT jongmanyoo organoidbasedepithelialtomesenchymaltransitionoemtmodelfromanintestinalfibrosisperspective |