Alveolus-on-a-Chip Model of Acute Radiation-Induced Lung Injury

Authors:

Michelle Yang, Yuncheng Man, Donald E. Ingber

Date Created:

2025-01-01

Course Title:

Professor:

Not specified

About Paper:

Exposure to ionizing radiation due to nuclear incidents, space Using this model, we performed a radiation dose-response study, travel, or cancer radiotherapy can result in acute radiation-inducedemonstrating that disease hallmarks, including cellular DNA lung injury (RILI), a condition characterized by pneumonitis and double-strand breaks, reactive oxygen species generation, pro- subsequent lung fibrosis. Animal models fail to recapitulate key inflammatory cytokine production, immune cell recruitment, and hallmarks of human pathophysiology, and there are currently no tissue barrier dysfunction, can be fully recapitulated and increase effective treatments for RILI. Here, we employ a human Lung in a radiation dose-dependent manner. We also performed bulk Alveolus Chip model of acute RILI for the development of novel RNA sequencing on the epithelial and endothelial cells to analyze radiation medical countermeasures. The Lung Alveolus Chip is a the post-radiation differentially regulated biological processes. microfluidic device composed of two parallel channels separated Importantly, using NeMoCAD (network model for causality- by an extracellular matrix-coated porous membrane lined with aware discovery), a machine learning-based computational tool human primary alveolar epithelial cells interfaced with human that analyzes the transcriptome network features of a diseased state primary lung microvascular endothelial cells. The epithelial cells and predicts gene targets and drugs to reverse the features of the areculturedinair,andtheendothelialcellsaresubjectedtomedium disease, we identified several existing FDA-approved drugs that flow, mimickingtheair-liquidinterfaceofhumanlungs. Rhythmic we are testing in the Lung Alveolus Chip. Future studies will breathing motions are simulated by applying cyclic suction to the focus on validating the cellular and molecular mechanisms of the side chambers of the flexible device, which reversibly stretches promising drug candidates using gene-based approaches, such as and relaxes the flexible porous membrane and attached cell layers. gene silencing and CRISPR-Cas9 technology.

Abstract:

Exposure to ionizing radiation due to nuclear incidents, space Using this model, we performed a radiation dose-response study, travel, or cancer radiotherapy can result in acute radiation-inducedemonstrating that disease hallmarks, including cellular DNA lung injury (RILI), a condition characterized by pneumonitis and double-strand breaks, reactive oxygen species generation, pro- subsequent lung fibrosis. Animal models fail to recapitulate key inflammatory cytokine production, immune cell recruitment, and hallmarks of human pathophysiology, and there are currently no tissue barrier dysfunction, can be fully recapitulated and increase effective treatments for RILI. Here, we employ a human Lung in a radiation dose-dependent manner. We also performed bulk Alveolus Chip model of acute RILI for the development of novel RNA sequencing on the epithelial and endothelial cells to analyze radiation medical countermeasures. The Lung Alveolus Chip is a the post-radiation differentially regulated biological processes. microfluidic device composed of two parallel channels separated Importantly, using NeMoCAD (network model for causality- by an extracellular matrix-coated porous membrane lined with aware discovery), a machine learning-based computational tool human primary alveolar epithelial cells interfaced with human that analyzes the transcriptome network features of a diseased state primary lung microvascular endothelial cells. The epithelial cells and predicts gene targets and drugs to reverse the features of the areculturedinair,andtheendothelialcellsaresubjectedtomedium disease, we identified several existing FDA-approved drugs that flow, mimickingtheair-liquidinterfaceofhumanlungs. Rhythmic we are testing in the Lung Alveolus Chip. Future studies will breathing motions are simulated by applying cyclic suction to the focus on validating the cellular and molecular mechanisms of the side chambers of the flexible device, which reversibly stretches promising drug candidates using gene-based approaches, such as and relaxes the flexible porous membrane and attached cell layers. gene silencing and CRISPR-Cas9 technology.

Source:

Harvard / Rebecca Xue, Pruthvi Gowda, Nika Danial / 2025

Topics:

lung, radiation, cell, model, alveolu, human, acute, using, rili, chip, epithelial, gene

Co-authors:

@michelleyang387 , @yunchengman388 , @donaldeingber389