A human lung alveolus-on-a-chip model of acute radiation-induced lung injury

Queeny Dasgupta, Amanda Jiang, Amy M. Wen, Robert J. Mannix, Yuncheng Man, Sean Hall, Emilia Javorsky and Donald E. Ingber ()
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Queeny Dasgupta: Boston Children’s Hospital and Harvard Medical School
Amanda Jiang: Boston Children’s Hospital and Harvard Medical School
Amy M. Wen: Wyss Institute for Biologically Inspired Engineering at Harvard University
Robert J. Mannix: Boston Children’s Hospital and Harvard Medical School
Yuncheng Man: Boston Children’s Hospital and Harvard Medical School
Sean Hall: Wyss Institute for Biologically Inspired Engineering at Harvard University
Emilia Javorsky: Wyss Institute for Biologically Inspired Engineering at Harvard University
Donald E. Ingber: Boston Children’s Hospital and Harvard Medical School

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Acute exposure to high-dose gamma radiation due to radiological disasters or cancer radiotherapy 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 RILI in vitro. Both lung epithelium and endothelium exhibit DNA damage, cellular hypertrophy, upregulation of inflammatory cytokines, and loss of barrier function within 6 h of radiation exposure, although greater damage is observed in the endothelium. The radiation dose sensitivity observed on-chip is more like the human lung than animal preclinical models. The Alveolus Chip is also used to evaluate the potential ability of two drugs - lovastatin and prednisolone - to suppress the effects of acute RILI. These data demonstrate that the Lung Alveolus Chip provides a human relevant alternative for studying the molecular basis of acute RILI and may be useful for evaluation of new radiation countermeasure therapeutics.

Date: 2023
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DOI: 10.1038/s41467-023-42171-z

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