New Organ-on-Chip Model Reveals How Airway Injury Triggers Vascular Dysfunction in COPD
Researchers developed REVAS, a modular organ-on-chip system that models interactions between respiratory and vascular cells under oxidative stress conditions relevant to chronic obstructive pulmonary disease (COPD). The platform combines airway epithelium, microvascular endothelium, and pulmonary artery endothelial cells co-cultured with support cells, enabling study of multicellular lung dynamics that prior in vitro models could not replicate. The findings establish a mechanistic link between airway epithelial injury and downstream vascular inflammation and remodelling, offering a human-relevant tool for COPD therapeutic research.
Scientists have created REVAS, a modular organ-on-chip platform designed to investigate how airway epithelial injury propagates vascular dysfunction in COPD. The system comprises two respiratory chips hosting airway epithelium and microvascular endothelium, plus a vascular chip with pulmonary artery endothelial cells co-cultured alongside smooth muscle cells, pericytes, and fibroblasts. At baseline, the multicellular environment enhanced vascular endothelial barrier function and promoted cell differentiation, with mural cells influencing endothelial cell-matrix interactions and metabolism, while respiratory cells supported endothelial aerobic respiration and a quiescent phenotype. When epithelial oxidative stress was induced using hydrogen peroxide, inflammatory gene expression was triggered across all cell types, accompanied by apoptotic, reparative, and pro-angiogenic signalling and elevated release of COPD-relevant cytokines including IL-6, TNF-β, IL-8, CCL5, CXCL9, PDGF, and TGF-β. Comparative analyses against existing COPD endothelial datasets confirmed that REVAS recapitulates key features of disease-associated endothelial dysfunction, lending validity to the model. The study addresses a longstanding gap in understanding why cardiovascular complications significantly worsen COPD morbidity and mortality, providing a platform for future mechanistic and drug-testing studies.
What's missing
The study is a preprint posted on bioRxiv and has not yet undergone peer review, so findings should be interpreted with caution. The oxidative stress model uses a single chemical stimulus (H2O2) applied acutely, which may not fully capture the chronic, heterogeneous oxidative burden seen in COPD patients. Long-term stability and reproducibility of the REVAS platform across independent laboratories has not yet been demonstrated.
What different sources said
- bioRxivCenter
Organ on chip model of respiratory vascular interactions under COPD relevant oxidative stress
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