Organ Chip System Designed to Simulate Smoking Effects

Small airway chip (Wyss Institute, Harvard University)

27 October 2016. A system that combines human airway tissue on a chip with components that simulate cigarette smoking is being developed to test treatments for lung disorders. A team from the Wyss Institute for Biologically Inspired Engineering at Harvard University describe the system in today’s issue of the journal Cell Systems.

Cigarette smoking has long been known to cause a number of lung diseases, including chronic obstructive pulmonary disease, or COPD, a progressive respiratory disorder that makes it difficult to breathe, and causes coughing, wheezing, shortness of breath, and tightness in the chest. In addition to cigarette smoking, other irritants like chemical fumes or air pollution can contribute to the condition.

One problem in developing new treatments for COPD and other lung disorders exacerbated by smoking is the lack of accurate models for diagnostics and assessing therapies. Lung cells in lab cultures do not behave in the same way as in their original tissue, and small animals often used in lab tests have different inflammatory responses than humans and breath through their noses, while human smoke enters through the mouth.

The Wyss Institute team led by the institute’s director Donald Ingber built the system around its recently completed work that devised a lung small airway-on-a-chip device. That device, as described in Science & Enterprise in December 2015, is a hand-held microfluidic chip that models the cellular architecture of the human small airway. The micro-channels in the chip are lined with the lung’s surface layer cells and specialized cell types exposed to air. The chip’s channels can also be lined with cells from COPD patients, which can then be compared to healthy human airway tissue.

Added to the airway-on-a-chip are a machine that smokes lit cigarettes and a miniature respirator to simulate the inhaling and exhaling of smoke and fresh air. The system can be configured to test the effects of vapors from electronic cigarettes as well as traditional tobacco.

Wyss Institute technology researcher and first author Kambez Benam says the system can capture the complex oxidant-induced responses of lung cells to toxic elements in cigarette smoke as well as inflammation characteristic of COPD. The system also analyzes the responses of cilia growing from small airway cells that normally transport mucus, when exposed to cigarette smoke.

“We identified a COPD-specific signature,” says Benam in a Wyss Institute statement, “by comparing gene expression changes in COPD-derived chips exposed or not exposed to smoke and subtracting the changes that we see in chips made from healthy lung chips. This type of analysis could lead to future biomarkers, drug targets, and possibly more personalized approaches to COPD in the future.”

Ingber adds that, “The power of the technology is that it allows us to directly analyze the effect of a stimulus, in this case smoke exposure, on lung in what might be thought of as an in vitro human ‘pre-clinical’ study.” In conventional clinical trials such comparisons are difficult, notes Ingber, since patients have different histories, backgrounds and patterns of cigarette smoke exposure.

Ingber and colleagues from Wyss Institute founded Emulate Inc., a spin-off enterprise, in 2014 to commercialize the institute’s work on organ chip models. One of its products is a small airway chip device like that used in the study. Staff from Emulate Inc. took part in the research team that developed the smoking simulator. Benam, Ingber, and other co-authors filed a patent application for the breathing-smoking lung chip technology.

In the following video, Benam and Ingber tell more about and demonstrate the smoking simulation system.

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