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

Authors

Elizabeth Oh, Esak Lee

Published in

Cell reports. Volume 45. Issue 10. Pages 118146. Oct 13, 2026. Epub Oct 13, 2026.

Abstract

High endothelial venules (HEVs) are specialized post-capillary venules that gate lymphocyte entry into lymph nodes, yet human in vitro models that capture their specialization remain limited. Here, we develop a perfusable human HEV-on-chip in which blood endothelial cells (BECs) form an engineered microvessel within a collagen-fibrin matrix populated by human fibroblastic reticular cells (FRCs). The presence of FRCs, without exogenous LIGHT, drives HEV-associated marker expression (PNAd/MECA-79 and VCAM-1) and a plump endothelial wall enwrapped by a thickened laminin⁺ basement membrane, recapitulating features of lymph-node HEVs. Functionally, HEV-like vessels support markedly increased T-lymphocyte adhesion while preserving VE-cadherin junctions. Introducing MDA-MB-231 breast cancer cells in an adjacent channel reduces MECA-79, disrupts junctional organization, and increases permeability without inducing apoptosis. Together, this platform defines a stromal instruction program for human HEV identity and a tractable model of cancer-associated HEV dysfunction.

PMID:
42873637
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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