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Lung-on-a-chip: a breath of fresh air in disease modelling

By Dr Isabel Goodhand, Science Writer, Alto Marketing – 13th November

The ultimate goal of the disease model is to mimic the disease state, and direct drug development at the pre-clinical stage. Human cell culture and animal models are the two main approaches relied upon at present. However, static 2D cell monolayers are hardly representative of the complex in vivo situation, while animal testing is a necessary evil that commonly falls short of reflecting the equivalent human condition. We may share most of our genome, but there are a number of fundamental distinctions to be drawn between mice and men.

In order to test novel treatments, we first need an accurate model…

The latest model

Enter the “organ-on-a-chip” revolution. Combining advances in 3D cell culture and bioengineering, selected organ functions are recaptured in the form of miniature artificial devices.

Last week, researchers at Harvard’s Wyss institute published a paper in Science Translational Medicine, describing a lung-on-a-chip model. They then used the device to study lung toxicity resulting from IL-2 anti-cancer treatment. Cancer therapies are notorious for extreme side effects, and IL-2 treatment is no exception. Lung toxicity is commonly observed as pulmonary oedema, where fluid seeps out of the blood flow to accumulate in the airspaces of the lungs, compromising gas exchange and leading to respiratory failure.

Lung-on-a-chip: mimicking conditions within the human lung with a device the size of a memory stick. A porous flexible membrane represents lung tissue, and separates two hollow channels equivalent to the airway (circulated with air), and blood supply (circulated with media). Human alveolar cells line the surface of the “airway”, while human capillary blood cells line the “blood” side. Simulating how lung tissue expands and contracts under the motion of normal breathing, the membrane is also distorted by a vacuum applied to adjacent side channels.

Incredibly, it was discovered that the mechanical forces of breathing motions increase membrane permeability and exacerbate pulmonary oedema. This factor, unaccounted for in standard cell culture, makes you wonder what other causal factors are missed in simplified disease models. Furthermore, the researchers also used the lung-on-a-chip to identify novel therapeutic compounds that alleviate this.

Admittedly, it’s not a perfect solution and there are many other factors at work for which only a complete human model would account for. However, this most recent innovation still represents a major advance in the realm of translational research, leading to insights that static cell culture or animal models simply cannot provide.

Obviously, developing a great new scientific product is fantastic; making sure that the relevant people know about it is the other half of the “marketing” equation. And that’s where Alto Marketing comes in…

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