A human lung alveolus-on-a-chip model of acute radiation-induced lung injury
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 interf...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-10-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42171-z |
| _version_ | 1827709895615447040 |
|---|---|
| author | Queeny Dasgupta Amanda Jiang Amy M. Wen Robert J. Mannix Yuncheng Man Sean Hall Emilia Javorsky Donald E. Ingber |
| author_facet | Queeny Dasgupta Amanda Jiang Amy M. Wen Robert J. Mannix Yuncheng Man Sean Hall Emilia Javorsky Donald E. Ingber |
| author_sort | Queeny Dasgupta |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:29:41Z |
| format | Article |
| id | doaj.art-6ae3452b30aa4654a34caaf5a5e810af |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:29:41Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-6ae3452b30aa4654a34caaf5a5e810af2023-11-20T10:03:58ZengNature PortfolioNature Communications2041-17232023-10-0114111410.1038/s41467-023-42171-zA human lung alveolus-on-a-chip model of acute radiation-induced lung injuryQueeny Dasgupta0Amanda Jiang1Amy M. Wen2Robert J. Mannix3Yuncheng Man4Sean Hall5Emilia Javorsky6Donald E. Ingber7Vascular Biology Program and Department of Surgery, Boston Children’s Hospital and Harvard Medical SchoolVascular Biology Program and Department of Surgery, Boston Children’s Hospital and Harvard Medical SchoolWyss Institute for Biologically Inspired Engineering at Harvard UniversityVascular Biology Program and Department of Surgery, Boston Children’s Hospital and Harvard Medical SchoolVascular Biology Program and Department of Surgery, Boston Children’s Hospital and Harvard Medical SchoolWyss Institute for Biologically Inspired Engineering at Harvard UniversityWyss Institute for Biologically Inspired Engineering at Harvard UniversityVascular Biology Program and Department of Surgery, Boston Children’s Hospital and Harvard Medical SchoolAbstract 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.https://doi.org/10.1038/s41467-023-42171-z |
| spellingShingle | Queeny Dasgupta Amanda Jiang Amy M. Wen Robert J. Mannix Yuncheng Man Sean Hall Emilia Javorsky Donald E. Ingber A human lung alveolus-on-a-chip model of acute radiation-induced lung injury Nature Communications |
| title | A human lung alveolus-on-a-chip model of acute radiation-induced lung injury |
| title_full | A human lung alveolus-on-a-chip model of acute radiation-induced lung injury |
| title_fullStr | A human lung alveolus-on-a-chip model of acute radiation-induced lung injury |
| title_full_unstemmed | A human lung alveolus-on-a-chip model of acute radiation-induced lung injury |
| title_short | A human lung alveolus-on-a-chip model of acute radiation-induced lung injury |
| title_sort | human lung alveolus on a chip model of acute radiation induced lung injury |
| url | https://doi.org/10.1038/s41467-023-42171-z |
| work_keys_str_mv | AT queenydasgupta ahumanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT amandajiang ahumanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT amymwen ahumanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT robertjmannix ahumanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT yunchengman ahumanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT seanhall ahumanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT emiliajavorsky ahumanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT donaldeingber ahumanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT queenydasgupta humanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT amandajiang humanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT amymwen humanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT robertjmannix humanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT yunchengman humanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT seanhall humanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT emiliajavorsky humanlungalveolusonachipmodelofacuteradiationinducedlunginjury AT donaldeingber humanlungalveolusonachipmodelofacuteradiationinducedlunginjury |