Animal testing alternative breakthrough
Scientists have partnered to create a liver-on-chip device mimicking human physiology.
Part-funded by the European Research Council and the European Commission, scientists at Israel’s Hebrew University of Jerusalem and Germany’s Fraunhofer Institute for Cell Therapy and Immunology hope the breakthrough will help move towards replacing the use of animals in research; presently, human cells rarely survive more than a few days outside the body. The research results mark the first discovery of a new toxicity mechanism using the newly emerging human-on-a-chip technology.
Speaking about the results, Professor Yaakov Nahmias, the study’s lead author and director of the Alexander Grass Center for Bioengineering at Hebrew University of Jerusalem, said: “The liver organs we created were less than a millimetre in diameter and survived for more than a month.
“We realised that because we are building the organs ourselves, we are not limited to biology, and could introduce electronic and optical sensors to the tissue itself. Essentially we are building bionic organs on a chip,” said Nahmias.
While other research groups displayed similar results, the breakthrough came when the groups added nanotechnology-based optoelectronic sensors to the living tissues, which enabled the group to identify a new mechanism of acetaminophen (Tylenol) toxicity.
The authors discovered that acetaminophen blocked respiration much faster and at a much lower dose than previously believed. The current understanding was that acetaminophen was broken to a toxic compound, called NAPQI, before damaging the cells. As the liver could naturally deactivate NAPQI, damage was thought to occur only at high doses and in cases of diseased or compromised liver function.
Professor Oren Shibolet, head of the liver unit at the Tel-Aviv Sourasky Medical Center, added his thoughts, though was not involved in the original study: “We knew that acetaminophen can cause nephrotoxicity as well as rare but serious skin reactions, but up until now we didn’t really understand the mechanism of such an effect. This new technology provides exceptional insight into drug toxicity, and could in fact transform current practice.”
The current study was released in the Archives of Toxicology journal.
