Use of advanced human lung culture models to study effects of radiotherapy

Pulmonary radiation toxicity is a main dose-limiting factor of radiotherapy for lung cancer, and manifests primarily as radiation-induced pneumonitis and fibrosis. A variety of mechanisms have been implicated in this toxicity, with a central role of DNA damage following radiation and formation of reactive oxygen intermediates (ROI), resulting in cellular stress, cell death and inflammation. The tissue repair process that is subsequently initiated may result in development of a pro-fibrotic environment, resulting in radiation-induced lung fibrosis.

Improved understanding of the mechanisms involved in this pulmonary toxicity is important for risk reduction and treatment. These mechanisms can be studied in patients and in animal models, and increasingly in vitro culture models are being employed. In recent years, there has been a rapid development of novel advanced patient- and disease-specific lung culture models, such as organoids and lung-on-chip. These are based on the use of primary cell cultures derived from lung tissue, or human induced pluripotent stem cell (hiPSC)-derived lung cells, and may include various cell types. During this presentation, the development and application of such airway and alveolar epithelial-centered lung models will be discussed, including their application in studies on photon and proton radiation.