09 November 2012

Lungs-on-a-chip will replace guinea pigs

The model of pulmonary edema was recreated on a chip

Copper news based on the materials of the Wyss Institute for Biologically Inspired Engineering:
"Lung-on-a-chip" sets stage for next wave of research to replace animal testingAmerican scientists have recreated a model of pulmonary edema on a polymer chip using cells of the human body.

The authors of the work called their model, developed for testing new drugs, "lungs on a chip". The results of research by scientists from the Wyss Institute of Bioengineering at Harvard University are published in the journal Science Translational Medicine (Huh et al., A Human Disease Model of Drug Toxicity-Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice).

The "lungs on a chip" are a parallelepiped made of a transparent, flexible polymer. Inside the parallelepiped, two channels are located above each other, separated by a thin porous membrane lined with lung cells on one side and capillary wall cells on the other.

The lower channel acts as a blood vessel – a fluid simulating blood flows through it; an air flow moves through the upper channel. The breathing cycle simulates a vacuum pump, after which the entire system recreates the compression and expansion of the lungs during breathing.

With pulmonary edema, blood plasma penetrates through the walls of the capillary into the air-carrying part of the lung, namely into the connective tissue (interstitium). Usually, the fluid entering the interstitium is eliminated by the lymphatic system, but when edema occurs, too much plasma seeps through the capillaries, which the lymphatic system no longer has time to remove. It is this process that scientists have recreated with the help of their model.

The identity of the behavior of the artificially created model and the human lungs has been proved experimentally. To do this, the researchers used an anti-cancer chemotherapeutic drug called interleukin-2, one of the side effects of which is the occurrence of pulmonary edema.

Scientists injected the drug into a liquid flowing through a capillary channel, after which the "plasma" began to penetrate through the membrane into the air–carrying part of the system - just as it happens with the development of pulmonary edema.

However, two important discoveries were made during the experiment. Firstly, the researchers concluded that the immune system is not involved in the occurrence of edema during treatment with interleukin-2. Secondly, scientists have found that the activation of respiratory processes in pulmonary edema contributes to an increase in the amount of fluid entering the interstitium through the capillary wall by more than three times. Subsequently, they confirmed this discovery in experiments on model animals.

"This model of pulmonary edema can be used to identify new therapeutic agents in vitro," said Donald Ingber, MD, director of the Wyss Institute of Bioengineering and lead author of the study.

Ingber and his colleagues are striving to ensure that the models of organs-on-a–chip – heart, intestines, kidneys and lungs - developed at the Institute could gradually become a replacement for animal drug testing. "Leading pharmaceutical companies spend a lot of time and spend a huge amount of money on cell cultures and testing new drugs on animals. But these methods are often unable to predict the effect of medicinal agents on the human body," Ingber stressed.

Portal "Eternal youth" http://vechnayamolodost.ru09.11.2012

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