Lung-on-a-Chip Used to Model Human Disease

Harvard researchers mimic pulmonary edema on a microchip

2 min read
Lung-on-a-Chip Used to Model Human Disease
Wyss Institute

A lung-on-a-chip looks nothing like a human lung: It's a clear, flexible piece of silicone rubber that's smaller than your thumb, with human lung cells growing inside the microscopic channels carved into it. But researchers have shown that this gizmo can not only mimic the essential functions of a healthy human lung, it can also be used to reproduce the conditions inside a diseased lung. This proof-of-concept research shows that organ-on-a-chip devices can aid medical research and drug development, and may reduce the need for animal testing in the future. 

The researchers hail from Harvard's Wyss Institute for Biologically Inspired Engineering, which is at the forefront of organ-on-a-chip research. We've covered prior triumphs from the Wyss researchers like their gut-on-a-chip, which mimicked human intestines and came complete with peristaltic motions, and their plans to link together ten different organ-chips to create a "human-on-a-chip." They describe their latest advance in the journal Science Translational Medicine

The lung-on-a-chip is fabricated using techniques learned from computer microchip manufacturing. Its channels have a porous matrix in the middle that host lung cells on one side, where air flows over them, and capillary cells on the other side, where a blood-like fluid flows over them. Vacuum pumps on both sides of the chip cause it to expand and contract, mimicking the way the human lung's air sacs expand and contract with every breath. 

In the latest research, the scientists reproduced the symptoms of pulmonary edema, a potentially deadly condition characterized by fluid and blood clots in the lungs. The cancer chemotherapy drug interleukin-2 (IL-2) is known to cause pulmonary edema in some patients, so the researchers introduced IL-2 into the lung-on-a-chip and watched to see what happened. Just as in a real lung, on the chip the drug caused fluid and proteins to cross over the matrix and leak into the air flow channel.

The researchers also tested a new class of drug that's being developed by GlaxoSmithKline to treat pulmonary edema symptoms. The drug was effective on the chip, and in a separate study the pharmaceutical scientists validated the results in animal experiments. These results suggest that organ-on-chip technology could soon reduce the need for animal testing, which is expensive, slow, and controversial. 

Donal Ingber, founding director of the Wyss Institute and a senior author of this study, spoke in a press release about the utility of this cutting-edge technology:

"In just a little more than two years, we've gone from unveiling the initial design of the lung-on-a-chip to demonstrating its potential to model a complex human disease, which we believe provides a glimpse of what drug discovery and development might look like in the future."

Images: Wyss Institute

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This CAD Program Can Design New Organisms

Genetic engineers have a powerful new tool to write and edit DNA code

11 min read
A photo showing machinery in a lab

Foundries such as the Edinburgh Genome Foundry assemble fragments of synthetic DNA and send them to labs for testing in cells.

Edinburgh Genome Foundry, University of Edinburgh

In the next decade, medical science may finally advance cures for some of the most complex diseases that plague humanity. Many diseases are caused by mutations in the human genome, which can either be inherited from our parents (such as in cystic fibrosis), or acquired during life, such as most types of cancer. For some of these conditions, medical researchers have identified the exact mutations that lead to disease; but in many more, they're still seeking answers. And without understanding the cause of a problem, it's pretty tough to find a cure.

We believe that a key enabling technology in this quest is a computer-aided design (CAD) program for genome editing, which our organization is launching this week at the Genome Project-write (GP-write) conference.

With this CAD program, medical researchers will be able to quickly design hundreds of different genomes with any combination of mutations and send the genetic code to a company that manufactures strings of DNA. Those fragments of synthesized DNA can then be sent to a foundry for assembly, and finally to a lab where the designed genomes can be tested in cells. Based on how the cells grow, researchers can use the CAD program to iterate with a new batch of redesigned genomes, sharing data for collaborative efforts. Enabling fast redesign of thousands of variants can only be achieved through automation; at that scale, researchers just might identify the combinations of mutations that are causing genetic diseases. This is the first critical R&D step toward finding cures.

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