"Lung-on-a-chip" technology can mimic the life-threatening condition pulmonary edema and holds the potential to become an alternative to animal testing for drug toxicity, according to a new study in Science Translation Medicine.
Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University introduced organ-mimicking chips two years ago, including the lung, heart, kidney and gut. A video of the "lung-on-a-chip" explains that within the thumb-sized device, a thin, porous membrane divides the space, with human lung cells exposed to air on one side and human capillary blood cells lining the other, with a medium flowing over them containing white blood cells. Vacuum chambers on the sides mimic the rhythmic expansion and contraction that occurs with breathing.
In the latest research, the researchers were able to create pulmonary edema, a condition in which fluid and blood clots fill the lungs, on the chip to make some surprising findings. By injecting the cancer chemotherapy drug interleukin-2, fluid and blood plasma proteins leaked across the membrane into the air channel, similar to the way it does in patients, reports MIT Technology Review.
Among the surprises: The immune system was not represented on the chip, but the leakage occurred anyway. The two had been thought to be related. And the leakage worsened three-fold with the breathing-like movements, which the researchers previously didn't know. That suggests that doctors using the drug with patients on a respirator should reduce the volume of air being pushed into the lungs, according to a Wyss announcement.
"In just a little more than two years, we've gone from unveiling the initial design of the lung-on-a-chip to demonstrating its potential to model a complex human disease, which we believe provides a glimpse of what drug discovery and development might look like in the future," senior author Donald Ingber said.
In a second study in Science Translation Medicine, a GlaxoSmithKline drug candidate was found to reduce pulmonary edema in mice with heart failure. The pharmaceutical company researchers also were also co-authors on the Wyss study.
And a separate perspective in the journal discusses how such cell-based models that mimic human biological processes have the potential to improve predictions of drug-related adverse events.
The work is further evidence that semiconductor technology is gaining traction in biomedical research. Previously, teams from the Massachusetts Institute of Technology and Stanford have developed chip-based tests to make diagnosis faster and easier.