While scientists have access to a myriad of methods and technologies to study the functionality of life at the cellular level, performing practical studies of biologic processes at the level of organs has been a challenge. Animal models, which have their own ethical and practical downsides, are typically used to do this research. A research team at the Wyss Institute for Biologically Inspired Engineering at Harvard University has announced the development of a tiny “lung-on-a-chip” that mimics some of the functions of the real organ at a small scale. They’re using it to study pulmonary edema, a disease involving the accumulation of fluid within the lungs.
The channels of the microfluidic chip are composed of human pulmonary epithelial and endothelial cells that have air and liquid flowing across. The cells themselves are also put under regular physical stress like that experienced within a real lung. They were able to induce pulmonary edema through drug toxicity using interleukin-2 (IL-2), a white blood cell regulator that’s used for immunotherapy of cancer patients.
More about the chip from the Wyss Institute:
The lung-on-a-chip device [see video], 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.
When IL-2 was injected into the blood channel 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 transport — just 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 [Donald Ingber, M.D., Ph.D., founding director of the Wyss Institute and senior author of the study] 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.
Flashback: Artificial Lung Without Need for Extra Oxygen
Link: Animation demonstrating the mechanics of the lung-on-a-chip…
Press release: “Lung-on-a-chip” sets stage for next wave of research to replace animal testing
Study in Science Translational Medicine: A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice
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