A human alveolus-on-chip model for radiation induced lung injury
Acute exposure to high-dose gamma radiation can result in radiation-induced lung injury (RILI), characterized by acute pneumonitis and subsequent lung fibrosis. A microfluidic organ-on-a-chip lined by human lung alveolar epithelium interfaced with pulmonary endothelium (Lung Alveolus Chip) is used to model acute, early stage RILI in vitro. Both lung epithelium and endothelium exhibit DNA damage, cellular hypertrophy, upregulation of inflammatory cytokines, and loss of barrier function within 6h of radiation exposure, and greater damage is observed in the endothelium. The alveolus chips are exposed to radiation injury at 16 Gy and shows effects that resemble the human lung greater than animal preclinical models. The Alveolus Chip is also used to evaluate the potential ability of two drugs to suppress the effects of acute RILI.  These data demonstrate that the Lung Alveolus Chip provides a human relevant alternative approach for studying the molecular basis of acute RILI towards screening radiation countermeasure therapeutics. Overall design: To assess the effect of radiation on the lung alveolar epithelium and the endothelium in a human lung alveolus chip. The study evaluates the effect of radiation on 2 cell types (human primary alveolar epithelium and lung microvascular endothelium) at two time-points (6 h and 7 d after radiation exposure). The controls are from human alveolus chips that receive no radiation exposure and are compared to alveolus chips that receive 16 Gy radiation. Each condition has 4 replicates: Alveolar epithelium (0 Gy) 6h, Alveolar epithelium (16 Gy) 6h, Microvascular endothelium (0 Gy) 6h, Microvascular endothelium (16 Gy) 6h, Alveolar epithelium (0 Gy) 7d, Alveolar epithelium (16 Gy) 7d, Microvascular endothelium (0 Gy) 7d, Microvascular endothelium (16 Gy) 7d