Cigarette smoke exposure is a major cause of human disease and a leading cause of death around the world. Although we know smoking causes lung disease, limitations with existing cell and animal models have hindered researchers from fully understanding the effect that smoking has on lung tissue.
Fortunately, researchers at the Wyss Institute, led by Dr. Don Ingber, Founding Director of the Wyss Institute for Biologically Inspired Engineering at Harvard University and mentor of a former NAVS/IFER fellowship recipient, may have a solution. Dr. Ingber and his team have developed a more promising human-relevant model to better understand how people respond to cigarette smoke exposure by coupling a breathing “lung-on-a-chip” device with a smoke machine that is able to mimic the actions of cigarette smokers.
While other cell-based models are available to study the exposure of lung cells to cigarette smoke, they expose cells to smoke from above the cells and do not mimic the natural lateral manner in which cells are typically exposed to smoke.
The use of animal models for these cigarette smoke exposure tests is also problematic, both scientifically—the presence of disease pathology in animal models is questionable—and ethically. We are all familiar with horrific images of scientific experiments in which animals are forced to ingest cigarette smoke. This type of research still takes place, particularly in the testing of e-cigarettes.
The most widely used animal models, however, receive exposure to smoke differently than humans do. Most animals used in smoke exposure studies are “obligate nose breathers” and don’t breathe through their mouths. In these studies, the animals get exposed to smoke passively when their cages are filled with smoke. Humans can be exposed to smoke in a more active manner, as we can breathe through our mouths.
The biomimetic smoking robot engineered by Dr. Ingber and his team overcomes such limitations and enables variables—including puffs per cigarette, puff duration and inter-puff intervals—to be adjusted in the model to more accurately simulate human cigarette smoking behavior. Researchers can then study the effect on cells exposed to the smoke as compared to cells that have not been exposed to it, to better understand how the lungs respond. This will be helpful in advancing drug development for lung diseases and to study toxicity profiles of tobacco-related products, such as e-cigarettes.
A new article, describing how to engineer, assemble and operate the biomimetic smoking robot was published in the journal Nature Protocols this month, providing researchers around the world with information on how to develop this animal-free model in their own labs.
NAVS is excited about the potential of the smoking lung-on-a-chip and how this sophisticated, in vitro tool is allowing researchers to model human smoke exposure without relying on animal models. Click here to watch a video of the smoking lung-on-a-chip.
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Benam, K. et al. “Biomimetic smoking robot for in vitro inhalation exposure compatible with microfluidic organ chips.” Nature Protocols. 2020