"In vivo chip" device for monitoring the side effects of anticancer drugs

Release date: 2017-08-29

Researchers at the Kyoto Institute of Integrated Cell Materials Science (iCeMS) at Kyoto University have designed a small "in-vivo chip" device that can test the side effects of drugs on human cells. The device addresses some of the current problems with similar microfluidic devices and provides hope for the next generation of preclinical drug testing.

Integrated heart/chip cancer (iHCC) is used to test the toxicity of the anticancer drug doxorubicin to heart cells. Researchers led by Ken-iichiro Kamei of iCeMS found that although the drug itself is not toxic to heart cells, the drug metabolites produced by interaction with cancer cells are toxic.

The device is smaller than the microscope slide. It consists of six cells; each two connects a series of inlets and valves through a microchannel. A pneumatic pump controls the movement of fluid through the passage. Each two rooms and their separate microchannel system form a test bench. The three test beds in the device allow small changes to be introduced on each bed to simultaneously compare the results.

The team first tested the effects of doxorubicin on heart cells and liver cancer cells isolated from small wells. The drug has the expected anticancer effect on cancer cells without causing damage to heart cells.

Then they run the test using the iHCC device. The heart cells are placed in one chamber while the liver cancer cells are placed in another chamber. Doxorubicin is introduced into the cell culture medium of the closed-loop system that connects the microchannels of the two chambers to simulate the circulatory system of the blood. In this way, the drug flows through the two chambers in a continuous loop in one direction.

The team found signs of toxicity in both cancer and heart cells. They hypothesized that compounds that act as metabolic by-products of interaction between doxorubicin and cancer cells cause toxic effects.

To test this, they added doxorubicin to the wells that cultured heart cells and liver cancer cells, respectively. It is toxic to heart cells but not to cancer cells.

When doxorubicin alone is added to liver cancer cells, the amount of by-products produced is too small to be toxic to heart cells. The team believes this is because the amount of cell culture medium required for testing will dilute the metabolite.

In contrast, when doxorubicin is introduced into iHCC, the metabolites are not diluted as they move through the microchannel circulatory system because of the smaller volume of cell culture required. Therefore, the drug does have a toxic effect on heart cells through its metabolites.

The device needs further improvement, but studies have shown how this design concept can be used to study the toxic side effects of anticancer drugs on heart cells before expensive clinical trials. The study was published in the journal Royal Institute of Chemical Progress.

Source: Noble

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