New Lung Chip Model Provides Insights into Radiation Damage to Lungs

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A team of researchers from the Wyss Institute for Biologically Inspired Engineering at Harvard University and Boston Children’s Hospital has developed an in vitro model that closely mimics radiation-induced lung injury (RILI). RILI is a common side effect of radiation therapy for cancer patients and can also occur following exposure to high radiation doses in nuclear accidents. The model, called the Lung Alveolus Chip, recaptures many of the hallmarks of RILI, including inflammation, injury to lung epithelial and blood vessel-lining endothelial cells, and radiation-induced DNA damage in lung tissue. The findings of the study are published in Nature Communications.

One of the major obstacles in understanding the pathological processes triggered by radiation in the lungs and developing medical countermeasures is the lack of experimental model systems that accurately replicate the damage that occurs in humans. Small animal preclinical models do not produce the same responses as humans, and non-human primate models are in short supply, costly, and raise ethical concerns. The Lung Alveolus Chip provides a human-relevant, preclinical model for studying RILI.

The Lung Alveolus Chip is a microfluidic culture system that consists of two channels. One channel contains primary human lung alveolar epithelial cells, which are exposed to air as they would be in the lungs. The adjacent channel contains primary human lung capillary endothelial cells, which are perfused with a blood-like nutrient medium. The chip also incorporates cyclic mechanical movements to mimic breathing motions. The lung chip can be exposed to clinically relevant doses of radiation and observed for the effects over an extended period of time.

When the Lung Alveolus Chip was exposed to increasing doses of radiation, the researchers observed breaks in the cells’ chromosomes and increased levels of reactive oxygen species. The cells also increased in size, and the barrier formed by endothelial and epithelial cells began to break down. The chip also exhibited an increase in pro-inflammatory cytokines, which is important for assessing radiation injury to the lungs. The chip provided insights into the early and later-stage inflammatory responses and identified a gene called HMOX1, which is involved in an anti-oxidant response and was upregulated following radiation exposure.

The researchers also evaluated the potential of two drugs, lovastatin and prednisolone, to suppress the effects of acute RILI. Lovastatin reduced DNA damage and cellular hypertrophy early after radiation, similar to prednisolone. However, later on, lovastatin worsened the disruption of the endothelial barrier. This suggests that targeting HMOX1 and other potential processes involved in RILI may require a more balanced therapeutic approach.

The Lung Alveolus Chip provides an advanced platform for studying RILI and developing potential treatment options. The team at the Wyss Institute plans to use similar models to investigate acute radiation damage in other organs and tissues. By linking different organ chips together, they hope to understand the effects of radiation damage on multiple organs. Additionally, personalized Lung Alveolus Chips could be used to study the hypersensitivities of patients predisposed to radiation due to other lung diseases. This research could lead to the development of medical countermeasures to protect against radiation-induced lung injury.

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  1. Source: Coherent Market Insights, Public sources, Desk research
  2. We have leveraged AI tools to mine information and compile it
Ravina
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Ravina Pandya,  Content Writer, has a strong foothold in the market research industry. She specializes in writing well-researched articles from different industries, including food and beverages, information and technology, healthcare, chemical and materials, etc. With an MBA in E-commerce, she has an expertise in SEO-optimized content that resonates with industry professionals.