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It’s pretty hard to smoke at Harvard University unless you are a small rubber block full of lung cells at the Wyss Institute. Then, it’s totally OK, because it’s in the name of science.

This block, called a lung-airway-on-a-chip, is connected to a respirator that mimics how humans smoke. It’s part of new technology created by Wyss researchers to study the effects of tobacco smoke and electronic cigarettes on lung cells.

“The smoke goes through this instrument, into the airway of our organ chip, and it comes out again, so that the chip experiences cigarette smoke as if a human is breathing and smoking at the same time,” said Dr. Don Ingber, founding director of the Wyss Institute and coauthor of the study, published Thursday in Cell Systems.


The chip has a hollow channel lined with cells from the small lung airways called bronchioles. To breathe and smoke cigarettes, a smoking machine that looks like the barrel of a Gatling gun holds up to 10 cigarettes, hooked up to a respirator that breathes in and out, passing smoke over the lung cells.

The smoking machine-lung chip setup could replace costly and time-consuming animal studies, said Ingber, and be used to hunt for patient-specific drug targets for smoking-related diseases. Scientists can do this, said lead author Kambez Benam, by splitting up a sample from a single person and putting them under two different conditions at the same time.


“We can have one set that can have smoke exposure, and another one that doesn’t have smoke exposure,” said Benam, a technology development fellow at the Wyss. “That’s one of the advantages of this technology for discovering genes or [drug] targets.”

For this study, Benam targeted chronic obstructive pulmonary disease (COPD), the third-leading cause of death worldwide. Smoking is the main cause of COPD, and there is no cure.

Researchers lined the chips with cells derived from COPD patients as well as unaffected people and filled the chambers with cigarette smoke. When they compared gene expression from the two pools of cells, they found 147 genes that were expressed differently in the COPD samples, compared to healthy cells.

The lung cells on the chip mimic actual lung tissue, complete with mucus and cilia, the small bristle-like projections that help sweep contaminants out of the lungs. In a look at how e-cigarette vapors might affect the function of the lungs, the team found that in normal lung cells, vaping had some effect on the way cilia moved. For this paper, they didn’t do the broad gene expression experiment that they did for cigarette smoke.

The researchers cautioned that the smoking machine doesn’t represent a complete lung and its interactions with other human organs and systems. They also said that they need to see how long-term exposure to cigarette smoke might affect lung cell physiology and gene expression.

Still, the system is useful, said Dr. Norman Edelman, senior scientific advisor for the American Lung Association, who was not involved with the study, especially if it can also be used to look at other bronchial irritants, which Ingber said is possible.

“I think it’s complementary, not an alternative,” Edelman said, adding that there may be some toxic interactions between cells and organs that researchers might miss by just looking at chips versus animal models.

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