Gut–Cartilage Chip and Osteoarthritis Organoid Metabolite Testing
A coupled intestinal–cartilage chip to study gut-derived soluble signals, followed by separate metabolite tests in osteoarthritis-derived cartilage organoids.
Multiple OrgansOrgan Chips
The Chinese University of Hong Kong Medical Centre, photographed in April 2024. (LN9267, CC BY-SA 4.0)
Research Applications
Comparing probiotic-conditioned gut effluent and identified metabolites as candidate modifiers of cartilage-organoid inflammatory and matrix responses.
Model & Design
A Caco-2 epithelial gut module linked to human bone-marrow-stromal-cell cartilage organoids; separate metabolite tests used cartilage organoids made from chondrocytes pooled from three osteoarthritis donors.
Experimental Format
Integrated gut–cartilage comparison with and without probiotic-conditioned effluent; individual metabolite testing in patient-derived cartilage organoids with the gut module empty.
Model Components
Component
Integrated chip model
Description
Separate intestinal and cartilage compartments linked by controlled perfusion; cartilage comparisons included probiotic-exposed and unexposed gut effluent.
Component
Patient-derived metabolite test
Description
Pooled chondrocytes from three osteoarthritis donors formed cartilage organoids; five individual metabolites were compared with untreated organoids over 72 hours.
Measurements & Endpoints
Gut barrier and cross-compartment transfer checks
Cartilage matrix and chondrogenic gene markers
Secreted IL-6, MMP13 and CTX-2
Cartilage inflammatory and hypertrophic markers
Analysis
Separate the integrated gut-effluent experiment from the direct compound experiment; treat independent chips as technical/experimental units rather than independent patients.
Published Evidence
Study Design
Probiotic-exposed gut effluent versus comparator chip conditions, followed by five separate metabolite treatments in pooled-donor OA cartilage organoids.
Study Sample
The OA chondrocytes came from three donors and were pooled; Figure 10B/C reports four independent chips per group and Figure 10F reports three, not additional independent donors.
Comparison
Untreated patient-derived cartilage organoids for direct metabolite testing; chip conditions without probiotic exposure for the integrated system.
Finding
Direct metabolite conditions reduced secreted IL-6, MMP13 and CTX-2 and altered cartilage-formation and degradation markers; reported effects varied by metabolite.
Interpretation & Limits
Pooled donor cells do not establish between-patient response variability.
The direct-metabolite phase left the gut module empty, so it did not test ongoing gut-to-cartilage effects.
A microbe–gut–cartilage chip linked a probiotic-exposed intestinal module to human cartilage organoids. Five enriched metabolites were subsequently tested on cartilage organoids made from pooled cells from three osteoarthritis donors.