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Updated: Jun 30, 2026
07:59
Adapting Gastrointestinal Organoids for Pathogen Infection and Single Cell Sequencing under Biosafety Level 3 (BSL-3) Conditions
Published on: September 10, 2021
Mesoscale maladaptation in disease organoids.
Masashi Okamoto1,2, Takanori Takebe1,3,4,5,6,7
1Department of Genome Biology, Graduate School of Medicine, and Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), the University of Osaka, Suita, Osaka 565-0871, Japan.
Disease Models & Mechanisms
|June 29, 2026
Summary
Chronic diseases involve multiple tissue failures. This study introduces mesoscale maladaptation, a framework to model synergistic decline in interdependent tissue functions for better in vitro disease research.
Area of Science:
- Biomedical Engineering
- Pathology
- Organoid Technology
Background:
- Chronic diseases often feature concurrent deterioration of multiple tissue components at shared interfaces.
- Disease progression in chronic conditions may stem from interactions between these failures, not just single defects.
- Current multi-tissue organoid models lack a simple framework for comprehensive analysis of these complex interactions.
Purpose of the Study:
- To propose mesoscale maladaptation as an operational concept for multi-tissue disease modeling.
- To define a stepwise workflow for detecting synergistic decline in interdependent tissue functions.
- To provide a framework for enriching biological insights into complex disease pathology.
Main Methods:
- Defined mesoscale maladaptation as synergistic decline in interdependent functions between two or more tissue elements.
- Developed a stepwise workflow to identify failing tissue elements and their interdependence.
- Compared combined perturbations with single perturbations to evaluate synergistic decline.
Main Results:
- Applied the framework to intestinal neuromuscular, hepatic sinusoidal, blood-brain barrier, and tumor-neural interfaces.
- Demonstrated the framework's utility in analyzing multi-tissue interactions in disease models.
- The framework facilitates the evaluation of synergistic pathology arising from concurrent multi-tissue failures.
Conclusions:
- Mesoscale maladaptation offers a new operational concept for multi-tissue disease modeling.
- The proposed framework enables comprehensive interrogation of complex disease pathology in vitro.
- This approach shifts focus from localized failures to concurrent, synergistic multi-tissue failures, advancing complex disease research.
