Human organ chip models recapitulate FRC-driven high endothelial venule differentiation, immune recruitment, and cancer-induced disruption.

Human organ chip models demonstrate FRC-driven HEV differentiation, immune recruitment, and cancer-induced disruption, with FRCs promoting HEV marker expression and structural features.

• Why it matters: Understanding human HEV formation and dysfunction is limited by in vitro models, hindering insights into lymphocyte trafficking and tumor immune evasion mechanisms.
• What they did: A perfusable human HEV-on-chip was developed using blood endothelial cells within a collagen-fibrin matrix populated by FRCs, with key HEV features driven by FRCs without exogenous LIGHT.
• The result: The model shows increased T-lymphocyte adhesion and preserved junctions in HEV-like vessels, while breast cancer cells reduce HEV marker expression, disrupt junctions, and increase permeability, enabling studies of HEV regulation and cancer effects.