Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have mimicked pulmonary edema in a microchip lined by living human cells, as reported today in the journal Science Translation Medicine. They used this "lung-on-a-chip" to study drug toxicity and identify potential new therapies to prevent this life-threatening condition.
The study offers further proof-of-concept that human "organs-on-chips" hold tremendous potential to replace traditional approaches to drug discovery and development.
"Major pharmaceutical companies spend a lot of time and a huge amount of money on cell cultures and animal testing to develop new drugs," says Donald Ingber, M.D., Ph.D., founding director of the Wyss Institute and senior author of the study, "but these methods often fail to predict the effects of these agents when they reach humans."
The lung-on-a-chip device, which the team first described only two years ago, is a crystal clear, flexible polymer about the size of a memory stick that contains hollow channels fabricated using computer microchip manufacturing techniques. Two of the channels are separated by a thin, flexible, porous membrane that on one side is lined with human lung cells from the air sac and exposed to air; human capillary blood cells are placed on the other side with medium flowing over their surface. A vacuum applied to side channels deforms this tissue-tissue interface to re-create the way human lung tissues physically expand and retract when breathing.
Wyss Technology Development Fellow Dongeun Huh, Ph.D., who also holds appointments at Boston Children's Hospital and Harvard Medical School, studied a cancer chemotherapy drug called interleukin-2or IL-2 for shortin the lung-on-a-chip. A major toxic side effect of IL-2 is pulmonary edema, which is a deadly condition in which the lungs fill with fluid and blood clots.
When IL-2 was injected into the blood channe
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Wyss Institute for Biologically Inspired Engineering at Harvard