Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
The liver is susceptible to foreign substances such as drugs and pathogens. Various in vitro hepatocyte models have been used to elucidate the pathophysiology of liver disease caused by exposure to foreign substances. However, the clinical predictability of drug evaluation tests using hepatocytes cultured in two-dimensional and static conditions is not enough high. Therefore, it is expected that the liver-on-a-chip developed using MPS technology that can reproduce three-dimensional and fluidic conditions will be used for pharmaceutical research. To establish a highly functional and practical liver-on-a-chip, technologies for manufacturing microfluidic devices and generating liver cells are indispensable. We mainly use the devices using polydimethylsiloxane (PDMS), but there is concern that PDMS is easy to absorb drugs. We found that the logD value of a drug can be used to predict the level of drug adsorption into the PDMS devices. Recently, we have developed a device using a low adsorption material, and have confirmed that it is possible to perform pharmaceutical research with almost no risk of drug adsorption by using this device. We have developed a liver-on-a-chip with vascular and bile duct structures by seeding liver cells such as hepatocytes, bile duct epithelial cells, and vascular endothelial cells in the device developed above. Using this liver-on-a-chip, not only drug toxicity and metabolism testing can be performed, but also the excretion of bile acid components and drugs into the bile duct channel can be evaluated. We are now conducting research on the pathophysiology of liver diseases caused by infection with pathogens such as SARS-CoV-2 using this liver-on-a-chip.
