US scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University have shown that their ‘lung-on-a-chip’ can mimic pulmonary edema, a life-threatening lung condition characterised by fluid and blood clots in the lungs. The scientists have reported that this technology can aid medical research and help identify potential new therapies. The chip may reduce the need for animal testing in the future.
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‘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,’ says Donald Ingber, founding director of the Wyss Institute and senior author of the study.
The lung-on-a-chip device is a clear, flexible block of silicone rubber with two tiny channels separated by a thin membrane. One channel is lined with human lung cells through which air flows; the other channel is lined with blood-vessel cells through which a blood substitute fluid flows. The channels are moved by a vacuum to re-create the way human lung tissues expand and contract when breathing.
The researchers injected a cancer chemotherapy drug interleukin-2 (IL-2) into the blood-vessel-like channel. The fluid and blood plasma proteins leaked across the membrane into the air channel, similar to the drug’s side effect in patients.
But one result that came as a surprise was that when the vacuum attached to the chip was turned on to simulate breathing, fluid leakage increased more than three-fold suggesting that breathing may make the condition worse. The pulmonary edema symptoms in the lung-on-a-chip disease model could be prevented by treating the tissues with TRPV4 channel blocker, a new class of drug being developed by GlaxoSmithKline.
‘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,’ says Donald Ingber, founding director of the Wyss Institute and senior author of the study.
The lung-on-a-chip device is a clear, flexible block of silicone rubber with two tiny channels separated by a thin membrane. One channel is lined with human lung cells through which air flows; the other channel is lined with blood-vessel cells through which a blood substitute fluid flows. The channels are moved by a vacuum to re-create the way human lung tissues expand and contract when breathing.
The researchers injected a cancer chemotherapy drug interleukin-2 (IL-2) into the blood-vessel-like channel. The fluid and blood plasma proteins leaked across the membrane into the air channel, similar to the drug’s side effect in patients.
But one result that came as a surprise was that when the vacuum attached to the chip was turned on to simulate breathing, fluid leakage increased more than three-fold suggesting that breathing may make the condition worse. The pulmonary edema symptoms in the lung-on-a-chip disease model could be prevented by treating the tissues with TRPV4 channel blocker, a new class of drug being developed by GlaxoSmithKline.
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