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Combining Human Organoids and Organ-on-a-Chip Technology to Model Intestinal Region-Specific Functionality

Combining Human Organoids and Organ-on-a-Chip Technology to Model Intestinal Region-Specific Functionality

Published on: May 5, 2022

Guiding Principles: Current Practices and Considerations for Benchmarking Human Gastrointestinal Organoids.

Monica E Brown¹, Antoine R Gleizes², Qianhui Yu³

¹Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Computational Systems Biology, Vanderbilt University, Nashville, Tennessee.

Cellular and Molecular Gastroenterology and Hepatology

|June 13, 2026

Summary

This summary is machine-generated.

Human gastrointestinal (GI) organoids are powerful models for studying gut biology and disease. This commentary addresses challenges and proposes a framework for benchmarking these organoids against native GI tract biology for improved accuracy.

Keywords:

Benchmarking Gastrointestinal Research Organoids Single-Cell RNA Sequencing

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Area of Science:

Gastroenterology and Hepatology
Developmental Biology
Tissue Engineering

Background:

Human small intestinal and colonic organoids, derived from primary tissues or pluripotent cells, have become increasingly accessible models for studying gastrointestinal (GI) biology and disease since 2011.
The growing use of organoids necessitates a thorough evaluation of their accuracy and limitations in representing native GI tract biology across diverse experimental settings.

Purpose of the Study:

To outline the current landscape and challenges in benchmarking human small intestinal and colonic organoids against native GI tract biology.
To propose a conceptual framework for multi-scale organoid benchmarking.
To review existing methods for assessing organoid-tissue similarities and discuss future directions for validating organoids as high-fidelity GI models.

Main Methods:

Review of current literature and established methodologies in organoid culture and analysis.
Development of a conceptual framework for systematic organoid benchmarking.
Discussion of current and emerging techniques for comparing organoid characteristics to native GI tissues.

Main Results:

Identified significant challenges in accurately representing native GI tract biology using current organoid models.
Presented a multi-scale conceptual framework to guide the benchmarking process.
Highlighted the need for standardized assays to assess similarities between organoids and their source tissues.

Conclusions:

Benchmarking human small intestinal and colonic organoids against native GI biology is crucial for ensuring their reliability as research models.
Standardized validation approaches are required to establish organoids as reproducible and high-fidelity models of the human GI tract.
Future research should focus on developing and implementing robust methods for organoid validation to advance GI research and disease understanding.