Rattling in the Lung Chip

18. August 2010
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If you want to know how drugs or toxics affect the lungs, you have to kill animals. Or built organ-on-chips supplying answers. A bit of synthetics, a good load of vacuum, add E. coli and you have a wonderful pneumonia in the tin.

Computer industry is your choice of contact if you want to work precisely without limits in the tiniest space. Donald E. Ingber, director at the Wyss Institute for biologically inspired engineering at Harvard Medical School in Boston/USA and his team of scientists came to the same conclusion. The researchers used the know how of the chip manufacturer to create a new bio-chip. To be precise: We are talking about a so-called “organ-on-a-chip”, an artificial lung copying structure and attributes of those alveolar small sacs no human being can go without to exchange gases or survive.

And he created the lung in its image…

The challenge here was – on one hand – to copy this cellular interface layer between air and blood vessels – certainly by using original materials i. e. epithelial cells of the alveoli and endothelial cells of the capillaries. But they also had to reproduce the mechanics of the lungs. Because the interface layer should breath, very similar to what the human lung does, while it’s slumbering in the thorax.

The trick which brought success for Ingber and his colleagues was a method of manufacture of this chip by a produced matrix with enclosed channels. In one of the channels, the interface layer made of alveolar cells and endothelial cells was recreated, one side air, the other fluid. The other channels served as connection points for kind of a miniaturized air pump: “We applied a vacuum there which leads to the cell layer expanding and retracting”, explains Ingbert. In other words: The model acts exactly like the alveolar wall when costal arch and diaphragm rise and fall. “Now we have the opportunity to examine the lung regarding pathogens or environmental toxins. Only then we can really understand how biology functions when we are able to place it physically-mechanically within the context of real organs. Applying vacuum imitates nature”, says Ingbert. As he reported in the professional magazine Science, Ingbert sees his lung model as a prototype for other organs which could be produced similarly. “It could provide and alternative to a large number of animal studies”, the expert emphasizes.

Wanted: Artificial pneunomia

By now the Harvard researchers have made initial experiments with the model. They were able to show that their simulation on a chip actually is relatively successful. They checked for example, what happens if the lung model is exposed to an infection with escherichia coli – a kind of simulated pneumonia so to speak. E. coli bacteria were blown through the air channel onto the lung side of the model. At the same time, the culture medium on the blood side was enriched with leukocytes. In a case like this, mother nature normally does what we call damage control. She sends off her defence cells out into the cold alveolar environment to save there whatever is possible. Actually it functions the same in the model. The alveolar cells recognized the bacteria and sent off a signal towards the blood vessels. As a result the leukocytes started marching through the rhythmically stretching and contracting alveolar wall. They destroyed the bacteria in the air compartment.

The next step: Personalized models for pharmaceutical research

After this success the scientists made yet another experiment. Instead of bacteria they blew nanoparticles into the lung model to find out what the simulated lung might do with them – once in a breathing stage and once without. “We found out that the activity of breathing increases absorption of nanoparticles significantly”, emphasizes Dan Huh, head of the project ‘simulated lung’. This fact was not really known so far.

The lung model of the Boston researchers still has a few vulnerable spots. For example it was not possible yet to show that a gas exchange is possible to simulate via the artificial alveolar wall. They are currently working on that. It might also be possible that the lungs of different people react differently to foreign objects. This issue is particularly fascinating: Because in principle it would be possible to use the patient’s own cells to create an organ model. Thus a lung model could be produced which operates exactly the same as the lung of the patient you are looking for a therapy for. And if you pack other organ models like intestines or liver on the same chip, pharmaceutical researchers are able to examine unwanted organ effects of a drug along with it. “Here really completely new doors are opening for the development of drugs”, Ingbert is convinced of.

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