源自人类诱导性多能干细胞（iPSC）的血管化肺类器官，用于模拟慢性阻塞性肺病（COPD）和肺动脉高压（PH）

Abstract

Vascularised lung organoids (vLOs) that faithfully mimic human lung tissue architecture and disease pathology are critical for advancing pulmonary research but remain challenging to generate. Here, we developed a robust self-organisation protocol to produce vLOs with cellular heterogeneity and functional vasculature. The engineered blood vessels within vLOs exhibit lung-specific characteristics. As proof of concept, we applied this platform to model chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH). Using patient-derived vLOs, we demonstrated that cigarette smoke extract (CSE) induces pathological features resembling clinical COPD, including epithelial disruption and inflammatory responses. Furthermore, vLOs generated from a PH patient recapitulated disease-associated vascular remodelling, with RNA-seq revealing dysregulated pathways in endothelial dysfunction. Notably, we identified sodium hydrosulfide (NaHS) as a potential therapeutic candidate, as it attenuated aberrant EndoMT in PH-vLOs. In summary, our study establishes a physiologically relevant vLO system that enables modelling of cell-type-specific disease mechanisms and underscores the broad utility of this platform for mechanistic investigations and precision medicine approaches in respiratory disorders.