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Evaluation of Intestinal Epithelial Barrier Function in Inflammatory Bowel Diseases Using Murine Intestinal Organoids

Tissue Engineering and Regenerative Medicine 2020년 17권 5호 p.641 ~ 650
Rallabandi Harikrishna Reddy, Yang Hyeon, 오건봉, 이휘철, 변성준, 이보람,
소속 상세정보
 ( Rallabandi Harikrishna Reddy ) - Rural Development Administration National Institute of Animal Science Animal Biotechnology Division
 ( Yang Hyeon ) - Rural Development Administration National Institute of Animal Science Animal Biotechnology Division
오건봉 ( Oh Keon-Bong ) - Rural Development Administration National Institute of Animal Science Animal Biotechnology Division
이휘철 ( Lee Hwi-Cheul ) - Rural Development Administration National Institute of Animal Science Animal Biotechnology Division
변성준 ( Byun Sung-June ) - Rural Development Administration National Institute of Animal Science Animal Biotechnology Division
이보람 ( Lee Bo-Ram ) - Rural Development Administration National Institute of Animal Science Animal Biotechnology Division

Abstract


Background: Intestinal organoids have evolved as potential molecular tools that could be used to study host-microbiome interactions, nutrient uptake, and drug screening. Gut epithelial barrier functions play a crucial role in health and diseases, especially in autoimmune diseases, such as inflammatory bowel diseases (IBDs), because they disrupt the epithelial mucosa and impair barrier function.

Methods: In this study, we generated an in vitro IBD model based on dextran sodium sulfate (DSS) and intestinal organoids that could potentially be used to assess barrier integrity. Intestinal organoids were long-term cultivated and characterized with several specific markers, and the key functionality of paracellular permeability was determined using FITC-dextran 4 kDa. Intestinal organoids that had been treated with 2 μM DSS for 3 h were developed and the intestinal epithelial barrier function was sequentially evaluated.

Results: The results indicated that the paracellular permeability represented epithelial characteristics and their barrier function had declined when they were exposed to FITC-dextran 4 kDa after DSS treatment. In addition, we analyzed the endogenous mRNA expression of pro-inflammatory cytokines and their downstream effector genes. The results demonstrated that the inflammatory cytokines genes significantly increased in inflamed organoids compared to the control, leading to epithelial barrier damage and dysfunction.

Conclusion: The collective results showed that in vitro 3D organoids mimic in vivo tissue topology and functionality with minor limitations, and hence are helpful for testing disease models.

키워드

Intestinal stem cells; Organoids; IBD; Epithelial barrier; Ex vivo model

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