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Engineering Large-Scale and Innervated Functional Human Gut for Transplantation.

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Biorxiv : the Preprint Server for Biology

|June 12, 2025

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This summary is machine-generated.

A novel confined culture system (CCS) generates functional human gastrointestinal tissues, including a developed enteric nervous system. This method accelerates organoid maturation and improves engraftment for disease modeling.

Area of Science:

Gastroenterology and Regenerative Medicine
Organoid Technology
Neurogastroenterology

Background:

Conventional organoids lack a functional enteric nervous system.
Generating complex human gastrointestinal tissues is time-consuming.
Existing methods limit the translational potential for disease modeling.

Purpose of the Study:

To develop a confined culture system (CCS) for generating complex, functional human gastrointestinal tissues.
To investigate the development of a de novo enteric nervous system within CCS-derived organoids.
To compare the maturation speed and engraftment efficiency of CCS organoids with traditional methods.

Main Methods:

Utilized a confined culture system (CCS) to culture human small intestinal, colonic, and gastric tissues.

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Characterized organoid development using transcriptomic and electrophysiological analyses.

Assessed organoid maturation, transplantation, engraftment, and in vivo functional augmentation with murine luminal content.

Main Results:

CCS successfully generated large-scale, innervated, tubular human gastrointestinal organoids.
Transcriptomic and electrophysiological data confirmed the co-development of a functional enteric nervous system.
CCS organoids matured in half the time of traditional methods, showing enhanced engraftment and size.
In vivo exposure to murine luminal content further improved organoid function.

Conclusions:

The CCS methodology simplifies protocols while enhancing the complexity and generation speed of clinically relevant gut tissues.
CCS enables the development of functional de novo enteric nervous systems in organoids, a key advancement over conventional methods.
This system holds significant translational potential for modeling complex intestinal diseases and advancing regenerative medicine.