Development of a Personalized Intestinal Fibrosis Model Using Human Intestinal Organoids Derived From Induced...

Area of Science:

• Gastroenterology
• Stem Cell Biology
• Fibrosis Research

Background:

• Intestinal fibrosis is a severe complication of Crohn's disease.
• Current research is limited by the lack of personalized in vitro models.
• Human intestinal organoids (HIOs) offer a potential solution by incorporating key intestinal cell types.

Purpose of the Study:

• To assess the feasibility of using induced pluripotent stem cell-derived HIOs for modeling intestinal fibrosis.
• To develop a personalized in vitro model for studying fibrotic responses in Crohn's disease.

Main Methods:

• Induced pluripotent stem cells (iPSCs) from healthy controls and Crohn's disease patients were used to generate HIOs.
• Epithelial and mesenchymal cells were isolated from HIOs and treated with transforming growth factor β (TGFβ).
• Gene expression analysis using quantitative PCR and RNA sequencing was performed.

Main Results:

• TGFβ treatment significantly increased profibrotic gene expression in iPSC-derived mesenchymal cells.
• RNA sequencing revealed differential profibrotic gene responses to TGFβ across patient lines.
• TGFβ also induced profibrotic genes and epithelial-mesenchymal transition markers in epithelial cells.

Conclusions:

• Induced pluripotent stem cell-derived HIO technology is feasible for modeling intestinal fibrotic responses in vitro.
• This approach enables the generation of patient-specific cells for studying intestinal fibrosis mechanisms.
• The model holds promise for personalized medicine approaches in Crohn's disease treatment.