Researchers at the Wyss Institute at Harvard University have developed a microfluidic chip that can recreate some of the features of radiation-induced lung injury. The lungs are very sensitive to radiation, and this can limit the application of radiotherapy to treat cancer. Accurately modeling radiation-induced lung injury could assist in developing new methods to prevent and treat the phenomenon, but it has been difficult to study this before the advent of advanced organ-on-a-chip models. The lung chip presented here contains human lung alveolar epithelial cells interfacing with lung capillary cells. The goal is to recreate the alveolar-capillary interface, and then by exposing the chip to radiation, the researchers can monitor the effects on these cellular populations in detail, as well as trying new treatments to reduce the effects of radiation.

The lungs are highly sensitive to radiation, with significant exposure resulting in radiation-induced lung injury. This manifests as sustained inflammation and fibrosis, which can affect lung function. This can be an issue for survivors of nuclear accidents, who may have inhaled contaminated particles, but it can also affect patients undergoing radiotherapy whereby dose limitation is required to avoid significant damage to the lungs. In any case, discovering how and why the lungs are so sensitive to radiation, and trialing new treatments offers hope for such patients.

The issue is that is has been difficult to study this phenomenon to date. Radiation-induced lung injury is a complex condition, and can vary significantly between patients based on a variety of risk factors. Moreover, animal models of the condition do not typically recapitulate its complex presentation and entail serious ethical concerns. In response, these researchers have developed an advanced in vitro system that can mimic some of the aspects of radiation-induced lung damage.

The chip is a microfluidic culture system that contains human lung alveolar epithelial cells in one channel, where they are exposed to air as in the lung, and another channel containing lung capillary endothelial cells that are exposed to a nutrient medium as a blood surrogate. This medium also contains immune cells, as they are relevant in radiation-induced injury. The two channels are separated by a semi-permeable membrane. The chip can be exposed to clinically relevant doses of radiation, and then the cellular responses can be measured.

The team quantified the appearance of so-called “DNA damage foci” created by the repair protein p53. Each visualized spackle represents one such foci, and the number of spackles in both, epithelial (top row) and endothelial cells (bottom row) increases with the radiation dose they applied to the alveolar-capillary interface on the chips. Credit: Wyss Institute at Harvard University

“Forming a better understanding of how radiation injury occurs and finding new strategies to treat and prevent it poses a multifaceted challenge that in the face of nuclear threats and the realities of current cancer therapies needs entirely new solutions,” said Donald Ingber, Wyss Institute Director. “The Lung Chip model that we developed to recapitulate development of radiation-induced lung damage injury leverages our extensive microfluidic Organ Chip culture expertise and, in combination with new analytical and computational drug and biomarker discovery tools, gives us powerful new inroads into this problem.”

Study in journal Nature Communications: A human lung alveolus-on-a-chip model of acute radiation-induced lung injury

Via: Wyss Institute

Source link