US scientists have managed to mimic pulmonary edema of the lungs in a microchip lined with living human cells.
Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University used a ‘lung-on-a-chip’ to study drug toxicity and identify potential new therapies to prevent pulmonary edema, which can be deadly as it causes a persons lungs to fill with fluid and blood clots.
The study provides further hope and evidence that an ‘organ-on-a-chip’ can be used successfully to speed up drug discovery by replacing lengthy and costly traditional practices.
The device is a crystal clear, flexible polymer about the size of a memory stick. It contains hollow channels fabricated using computer microchip manufacturing techniques. Two of the channels are separated by thin, flexible, porous membrane that is lined on one side with human cells from the air sac on one side and human capillary blood cells on the other side.
A vacuum is applied to side channels that deform the tissue-tissue interface to re-create the way human lung tissues physically expand and retract when breathing.
"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," said Wyss Institute founding director and study senior author Dr Donald Ingber.
A cancer chemotherapy drug called interleukin-2, of which pulmonary edema is a side effect, was injected in the ‘lung-on-a-chip’ to see if it would developed the condition. The drug produced the same side effects on the chip as it does to a human lung – fluid leakage, reduced volume of air, compromised oxygen transportation and blood clots in the air space.
The researchers then discovered that the act of breathing greatly enhances the effect of the drug in pulmonary edema, suggesting that doctors treating patients on a respirator with interleukin-2 should reduce the tidal volume of air being pushed into the lungs, to minimise the negative side effects of the drug.
Dr James Anderson, who was part of a support team for the researchers, said; "Organs-on-a-chip represents a new approach to model the structure, biology, and function of human organs, as evidenced by the complex breathing action of this engineered lung. This breathing action was key to providing new insight into the etiology of pulmonary edema.
"These results provide support for the broader use of such microsystems in studying disease pathology and hopefully for identifying new therapeutic targets."
The research was funded by the National Institutes of Health (NIH), the Food and Drug Administration (FDA), Defense Advanced Research Projects Agency (DARPA) and the Wyss Institute for Biologically Inspired Engineering at Harvard University.
Image: The university believe organs-on-a-chip could speed up drug discovery in the future. Photo: Courtesy of Wyss Institute for Biologically Inspired Engineering at Harvard University.
