* Study offers proof that new devices can mimic disease
* Companies see way to test drugs for toxic side effects
By Julie Steenhuysen
CHICAGO, Nov 7 (Reuters) – 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.”
