U.S. researchers have begun testing drugs using a microchip lined with
living cells that replicates many of the features of a human lung, a technology
that may one day help improve drug testing and reduce researchers' dependence
on animal studies.
In 2010, researchers at Harvard's Wyss Institute for Biologically
Inspired Engineering developed the so-called lung-on-a-chip technology that
mimics the function of air sacs called alveoli, which transfer oxygen through a
thin membrane from the lung to the blood.
For drug companies, the technology offers a way to better predict how
drugs will work in people, ultimately reducing the cost of drug development by
identifying problems before drugs are tested in clinical trials. "Major
pharmaceutical companies spend a lot of time and a huge amount of money on cell
cultures and animal testing to develop new drugs, but these methods often fail
to predict the effects of these agents when they reach humans," Dr. Donald
Ingber, whose study was published on Wednesday in Science Translational
Medicine, said in a statement.
Now the Wyss team is putting its artificial lung to the test, using the
device to recreate pulmonary edema, a condition that causes fluid to leak into
the air sacs of the lungs, and then treating it with an experimental drug from
GlaxoSmithKline. The device, which is about the size of a memory stick, is made
of a flexible polymer that contains hollow channels. These channels are divided
by a thin, permeable membrane lined on one side with human lung cells and on
the other with tiny blood vessel or capillary cells that are bathed in fluid to
simulate blood flow. A vacuum is applied to recreate the way human tissue
stretches during breathing.
For the study, the team treated the device with interleukin-2 or IL-2, a
cancer drug that can cause pulmonary edema, a deadly condition in which the
lungs fill with fluid and blood forms clots. When injected into the blood
channel of the device, the drug caused fluid to start leaking across the
membrane, reducing the amount of volume of air in the other channel. Blood
plasma crossed into the air channels and started to clot.
Dr. Geraldine Hamilton, co-author on the paper and the senior lead for
the organs on chips program at Wyss, said the study is "providing us with
a very exciting proof of concept for our ability to use organs on chips to
create human disease models." When the team turned on the vacuum to simulate
breathing, fluid leakage increased, suggesting that breathing may make the
condition worse.
"We learned more about the mechanisms by which this happens. Than
really wouldn't have been possible through an animal model," Hamilton
said. The team next used their model to test a new class of drug being
developed by GlaxoSmithKline called a TRPV4 channel blocker. They found that
treating the tissues in the device with the Glaxo drug before exposing it to
IL-2 prevented blood vessel leakage in the device.
To confirm this finding, Kevin Thorneloe, a scientist at
GlaxoSmithKline, did a parallel study in which he tested the drug in the lungs
of rodents and dogs with pulmonary edema caused by heart failure and found the
drug improved lung function and reduced leakage, consistent with the chip
finding. "These findings suggest that TRPV4 blockers could be used to
limit pulmonary edema in patients with heart or lung disease, and were an
important step toward validating the lung on a chip model," said
Thorneloe, whose companion study was published in the same journal. "This
technology is still in its early stages of development," he said, noting
that several additional studies will be needed to further validate the chip
device.
Although initially, such devices will be used to support early research
seeking to get a better understanding of disease at the molecular level,
Thorneloe said over time, they could be used to quickly study the impact of
several drugs on lung function. In July, Wyss entered a $37 million agreement
with the U.S. defense department to help develop 10 engineered organs, all
linked into one system. The idea is to replicate a human body on a chip, which
could be used to rapidly assess responses to new drugs and potential chemical
threats.
Donna Dambach, a pre-clinical safety scientist at Roche's Genentech
unit, said she thinks drug companies will be quick to adopt these technologies
for their own internal decision-making. But Dambach said it will likely take
much longer for drug companies to replace animal models used for regulatory
approval with these engineered organs. "I think everyone would love that,
but animals are complex, like human beings, and we really have to make certain
that we're at least predicting some level of that complexity in these
systems."
Source: Chicago Tribune
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