Research ArticlesBioengineering

A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice

Science Translational Medicine  07 Nov 2012:
Vol. 4, Issue 159, pp. 159ra147
DOI: 10.1126/scitranslmed.3004249

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Pulmonary Edema-on-a-Chip

Drug testing in animal models is time-consuming, costly, and often does not accurately predict the adverse effects in humans. Toward a more reliable output, Huh and colleagues developed a “lung-on-a-chip” that models human lung function in both normal and disease states.

The authors cultured two types of human lung cells in parallel microchannels, which were separated by a thin membrane. Much like the human lung, the upper “alveolar” channel was filled with air, whereas the lower “microvascular” channel was filled with liquid. Vacuum was cyclically applied to the sides of the channels to mimic the breathing motion of the lung. When Huh and colleagues added interleukin-2 (IL-2) to the microvascular channel, the fluid started to leak into the air compartment. This process reproduces what is seen in the clinic, where IL-2 induces pulmonary leakage, also known as “edema.” Cyclic mechanical strain introduced with IL-2 compromised the pulmonary barrier even further and led to a threefold increase in leakage. As expected, the addition of angiopoietin-1 stabilized the endothelial junctions and inhibited IL-2–induced vascular leakage. Lastly, the authors tested their pulmonary disease model against a new pharmacological agent, GSK2193874, which blocks certain ion channels activated by mechanical strain. This drug inhibited leakage, suggesting that it would be a viable treatment option for patients with pulmonary edema who are being mechanically ventilated.

Huh et al. have recreated the human lung on a microfluidic chip and shown that it not only mimics lung function in response to IL-2 and mechanical strain but also successfully predicts the activity of a new drug for pulmonary edema. The beneficial effects of GSK2193874 still need to be confirmed in humans, but were preliminary validated in animals in a study by Thorneloe et al. (this issue). The next step is to hook this lung up to other chip-based organs—heart, liver, pancreas, etc.—with the goal of one day being able to rapidly screen many drugs and conditions that could affect patient health.