Gut-liver-axis microphysiological system for studying cellular fluidic shear stress and inter-tissue interaction

Area of Science:

• Biomedical Engineering
• Organ-on-a-chip Technology
• Physiological Modeling

Background:

• The gut-liver axis (GLA) plays crucial roles in human health and disease.
• Current GLA microphysiological systems (GLA-MPS) lack physiologically relevant flow conditions.
• Integrating perfusion, circulation, and tissue function in a single device remains a challenge.

Purpose of the Study:

• To develop an advanced GLA-MPS with physiologically relevant flow.
• To enable the study of gut-liver interactions in vitro.
• To model diseases involving inter-tissue communication.

Main Methods:

• Designed a GLA-MPS with dual perfusion chambers and an integrated circulation channel with a micropump.
• Utilized computational fluid dynamics to confirm physiologically relevant fluid shear stress (FSS) for gut (Caco-2) and liver (HepG2) cells.
• Recapitulated inflammatory bowel disease using lipopolysaccharide (LPS) stimulation.

Main Results:

• Achieved physiologically relevant FSS for both cell types (gut: 8×10⁻³ dyn cm⁻², liver: 1.2×10⁻⁷ dyn cm⁻²).
• Maintained high cell viability (Caco-2: 95%, HepG2: 92%) under relevant flow conditions.
• Enhanced functional protein expression (zonula occludens 1, albumin) and induced inflammatory markers (inducible nitric oxide synthase) in both cell types upon LPS stimulation.

Conclusions:

• The developed GLA-MPS provides a physiologically relevant in vitro platform for studying gut-liver interactions.
• This system accurately models disease states, such as inflammatory bowel disease, by mimicking inter-tissue communication.
• The GLA-MPS is a valuable tool for advancing research in diseases involving the gut-liver axis.