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Generation of hiPSC-Derived Intestinal Organoids for Developmental and Disease Modelling Applications
Published on: March 8, 2024
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Human intestinal organoid models for celiac disease research
Valeriia Dotsenko1, Amir-Babak Sioofy-Khojine2, Heikki Hyöty3
1Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere University Hospital, Tampere, Finland.
Methods in Cell Biology
|August 25, 2023
Summary
Celiac disease involves duodenal epithelial changes triggered by gluten. Patient-derived intestinal organoids offer a superior model for studying these pathogenic mechanisms compared to traditional cell lines.
Area of Science:
- Gastroenterology and Immunology
- Epithelial Biology
- Celiac Disease Pathogenesis
Background:
- Celiac disease pathogenesis involves duodenal epithelial dysfunction beyond immune cell responses.
- Gluten exposure in celiac patients alters epithelial differentiation and cytokine responses.
- Transglutaminase 2 (TG2) enzyme's role in gliadin deamidation within the intestinal epithelium is implicated.
Purpose of the Study:
- To address limitations of current in vitro models for studying celiac disease.
- To introduce intestinal organoids as a more physiologically relevant model for celiac disease research.
- To provide protocols for establishing and utilizing patient-derived organoid cultures.
Main Methods:
- Development of protocols for initiating and maintaining celiac patient-derived intestinal organoid cultures.
- Adaptation of organoid culture methods for diverse experimental applications.
- Utilizing near-native epithelial cell models that overcome limitations of cancer cell lines.
Main Results:
- Established functional intestinal organoid cultures from celiac patient biopsies.
- Demonstrated the suitability of organoids for studying gluten-induced epithelial changes.
- Highlighted the advantages of organoids over traditional cell lines for differentiation studies.
Conclusions:
- Intestinal organoids represent a significant advancement in modeling celiac disease pathogenesis.
- These patient-derived organoids provide a powerful tool for investigating gluten-related epithelial responses.
- The described protocols enable broader application of organoids in celiac disease research.
