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Harvard's Wyss Institute models a human disease in an organ-on-a-chip
Date:11/7/2012

l of the lung-on-a-chip, fluid leaked across the membrane and two tissue layers, reducing the volume of air in the other channel and compromising oxygen transportjust as it does in lungs of human patients when it is administered at the equivalent doses and over the same time course. Blood plasma proteins also crossed into the air channel, leading to the formation of blood clots in the air space, as they do in humans treated with IL-2.

But one result came as a surprise.

It turns out the physical act of breathing greatly enhances the effects of IL-2 in pulmonary edema --"something that clinicians and scientists never suspected before," Ingber says. When the team turned on the vacuum attached to the chip to simulate breathing, it increased fluid leakage more than three-fold when treated with the clinically relevant IL-2 dose, and the Wyss team confirmed that the same response occurs in an animal model of pulmonary edema. This result could suggest that doctors treating patients on a respirator with IL-2 should reduce the tidal volume of air being pushed into the lungs, for example, in order to minimize the negative side effects of this drug.

Most exciting for the future of drug testing was the Wyss team's finding that "this on-chip model of human pulmonary edema can be used to identify new potential therapeutic agents in vitro," Ingber says. The pulmonary edema symptoms in the lung-on-a-chip disease model could be prevented by treating the tissues with a new class of drug, a transient receptor potential vanilloid 4 (TRPV4) channel blocker, under development by GlaxoSmithKline (GSK). In a separate study published by the GSK team in the same issue of Science Translation Medicine, the beneficial effects of TRPV4 inhibition in reducing pulmonary edema were independently validated using animal models of pulmonary edema caused by heart failure.

"In just a little more than two years, we've gone from unveiling the initial desi
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Contact: Kristen Kusek
kristen.kusek@wyss.harvard.edu
617-432-8266
Wyss Institute for Biologically Inspired Engineering at Harvard
Source:Eurekalert  

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