Work

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

Year: 2026

Type: article

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.

Source: Cell Reports

DOI: 10.1016/j.celrep.2026.118146

Authors: Elizabeth Oh, Esak Lee

Institution: Cornell University

Language: English

Topic: 3D Printing in Biomedical Research

Subfield: Biomedical Engineering

Field: Engineering

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,620