Patient-Derived Synovium-on-a-Chip Recapitulates Disease and Treatment Response and Permits Study of Resistance

A vascularized, immunocompetent rheumatoid arthritis synovium-on-a-chip recapitulates patient inflammation and predicts clinically matched response, with on-chip scores correlating to {Delta}DAS28-ESR (Pearson r = 0.844).

• Why it matters: Interpatient heterogeneity in RA synovial pathology and treatment response creates an unmet need for reliable, patient-specific drug efficacy testing.
• What they did: The team integrated patient-derived fibroblast-like synoviocytes with matched peripheral blood leukocytes, then tested infliximab, tocilizumab, and tofacitinib while combining cytokine secretion, extracellular matrix remodeling, immune survival, and recruitment into a composite response score.
• The result: Single-cell RNA sequencing linked persistent SFRP1 remodeling FLS and reduced FN1-CD44 signaling to higher NF-{kappa}B activity and drug resistance, and fibronectin supplementation in chips from an independent TNFi-nonresponsive patient reduced IL-6 secretion and restored the composite response.

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