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...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2017-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-02190-5
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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.
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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
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