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Dec 13, 2012
 |  BC Innovations  |  Tools & Techniques

Pulmonary edema on a chip

Researchers at the Harvard University have described the first disease model to emerge from the institute's organ-on-a-chip microfluidic device technology.1,2 The model of pulmonary edema could be better than culture models at predicting whether therapeutics will translate to humans.

The team already has used the lung-on-a-chip model in proof-of-concept studies to test potential pulmonary edema therapeutic candidates including GlaxoSmithKline plc's GSK2193874, an inhibitor of transient receptor potential vanilloid 4 (TRPV4; VRL2),3 and wants to expand the use of the chip to model multiple lung diseases.

GSK2193874 was also proven effective in a mouse model of pulmonary edema, validating the results that were found in the chip model (see Box 1, "TRPV4 inhibition").

The microfluidics system on a chip is about 2 cm long and mimics the alveolar-capillary interface and mechanical effects of breathing. The device is composed of two channels-a layer of human alveolar epithelial cells exposed to air and pulmonary microvascular endothelial cells exposed to flowing culture medium.

The channels are separated by a porous polymer-coated extracellular matrix. The channel interface is bordered by two chambers that can deform the polymer membrane upon application of a vacuum to mimic the mechanical effects of breathing.

Notably, the ability to simulate the mechanics of breathing is absent in 3D culture models of the lung.

Previous studies by the Boston team showed that the model can replicate the key physiological features of lung function, but it was unknown whether the device could model pulmonary diseases.2,4

Now, Donald Ingber and colleagues have generated a model that captures features of edema, provides insights into disease mechanisms and can help assess therapeutic candidates.

Ingber is a professor of vascular biology at Harvard Medical School and Boston Children's Hospital, professor of bioengineering at Harvard University and director of the Wyss Institute.

Pulmonary edema involves the abnormal accumulation of...

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