Release date: 2017-08-30
Recently, the Integrated Cell Materials Research Institute (iCeMS) of Kyoto University in Japan has designed a body-on-a-chip device that can test the side effects of drugs on human cells. The device addresses some of the current problems associated with microfluidic devices and provides new ideas for the next generation of preclinical drug trials. The study was published on the Royal Society of Chemistry Advances on August 24.
Pre-clinical trials of microfluidic devices in place of animals
Nowadays, the development of new pharmaceutical products, including anticancer agents, has many difficulties and requires huge expenses and long-term time. Among these reasons, a particular problem is the pre-clinical trial. In the pre-clinical test before the clinical trial, there are evaluations of the efficacy of the experimental animals, toxicity evaluation tests, and the like. However, it shows that there are many different reactions with humans, so it is difficult to predict the efficacy and toxicity in clinical trials. In addition, the use of experimental animals involves animal protection and is also an ethical issue. Therefore, the development of new test methods has become important to reproduce the reaction of the agent with humans and without animal experiments.
The Kyoto University study used "microfluidic devices" to achieve this goal. Using this device technology, it is possible to mimic the vascular network and tissue in the human body. On this device, cancer cells of human origin and normal cardiomyocytes are carried, and tissues can be connected.
One chip carries two cells that are connected to each other.
This device for detecting heart/cancer on a single chip (iHCC) was used to test the toxicity of the anticancer drug doxorubicin to cardiomyocytes. Researchers led by Ken-ichiro Kamei of iCeMS found that when the drug itself is not heart cytotoxic, the interaction of the drug's metabolites with cancer cells can cause toxicity.
The device is smaller than the microscope slide. It consists of six chambers; each two is connected by a series of inlets and valves, channels. A pneumatic pump controls the flow of fluid in the passage. Each of the two chambers and the respective microchannel system constitutes a test bed. The presence of three test beds in the equipment allows small changes to be introduced in each bed to simultaneously compare the results.
Such a system is more sensitive than cell culture
The team first tested the effects of doxorubicin with separately cultured heart cells and liver cancer cells. The drug has an anticancer effect on cancer cells and does not cause myocardial cell damage.
Then they use the iHCC device to test. Heart cells are placed in one chamber and liver cancer cells are placed in the other. Doxorubicin is introduced into the cell culture medium and circulated through a microchannel closed-loop system that connects the two chambers, mimicking the blood circulatory system. In this way, the drug flows in one direction in a continuous cycle through the two chambers.
The team found signs of toxicity in both cancer cells and heart cells. They speculate that doxorubicinol, a metabolic byproduct of the interaction between doxorubicin and cancer cells, is responsible for the toxic effects.
To test this, they added doxorubicinol to separately cultured heart cells and liver cancer cells and found it to be toxic to heart cells rather than cancer cells.
When doxorubicin is added to liver cancer cells alone, the amount of doxorubicinol produced is too small to be toxic to cardiomyocytes. The team believes this is because the amount of cell culture medium required for the test dilutes the metabolites.
In contrast, when doxorubicin is introduced into iHCC, the flow through the microchannel circulatory system causes the volume of the desired cell culture medium to be small, while the metabolite is not diluted. Therefore, the drug has a toxic effect on cardiomyocytes through its metabolites.
This is a new design concept
The device needs further improvement, but this study suggests that this design concept can be used to study the toxic side effects of anticancer drugs on heart cells before expensive clinical trials. This is the first successful example of connecting multiple organizations on a chip and confirming interactions. This is a model of human in vitro drug mimicry. The function of this new "human body model" device has been confirmed in research and has broad prospects.
Source: Bio-Exploration
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