Reprogramming human urine cells into intestinal organoids with long-term expansion ability and barrier function

Area of Science:

• Biotechnology
• Stem Cell Biology
• Gastroenterology

Background:

• Intestinal organoids are valuable for studying gut diseases and developing treatments.
• Generating patient-specific organoids is crucial for personalized medicine.

Purpose of the Study:

• To establish a direct reprogramming protocol for generating human urine cell-induced intestinal organoids (U-iIOs).
• To characterize the properties and potential applications of U-iIOs for intestinal regeneration, disease modeling, and drug screening.

Main Methods:

• Direct reprogramming of human urine cells into intestinal organoids using a defined medium.
• Gene expression profiling to compare U-iIOs with primary intestines and other organoid models.
• Functional assays to assess intestinal barrier properties and differentiation potential.

Main Results:

• Successfully generated U-iIOs that express key intestinal-specific genes and mimic primary small intestine gene expression.
• Demonstrated stable long-term expansion and differentiation of U-iIOs into mature intestinal lineage cells.
• Confirmed functional intestinal barrier characteristics in U-iIOs, including FITC-dextran blocking and rhodamine 123 uptake.
• Highlighted distinct molecular features of U-iIOs compared to pluripotent stem cell-derived organoids and immortalized cell lines.

Conclusions:

• Urine-induced intestinal organoids provide a novel, patient-specific platform for intestinal research.
• U-iIOs hold significant potential for advancing precision treatment of intestinal diseases and facilitating drug discovery.
• This method offers a more accessible source for generating patient-specific intestinal organoids compared to other stem cell-based approaches.