• Monday, July 22, 2019 @ 12:00 am

Findings represent key milestone in PATROLS initiative to establish tools for evaluating health and environmental risks of nanomaterials.

In a new study published in Scientific Reports, scientists from the Nano-Safety Research Group at the Heriot-Watt University and InSphero AG evaluated 3D cell-based liver models for predicting adverse effects caused by chronic exposure to engineered nanomaterial (ENM). The research team, led by Heriot-Watt Professor Vicki Stone, a particle toxicology expert, investigated how the presence and inter-donor variability of liver immune cells (specifically, Kupffer cell populations) governs the hepatic response to ENMs. The study, conducted as part of the EU-funded project Physiologically Anchored Tools for Realistic nanomaterial hazard aSessment (PATROLS), established InSphero 3D InSight™ Multi-Donor Human Liver Microtissues as a valuable nanotoxicology risk assessment tool.


ENMs, which are commonly used in consumer products ranging from sunscreens and cosmetics to clothing and sports gear, have unique physical characteristics that can induce toxic responses, particularly in organs involved in nanoparticle accumulation and subsequent clearance, such as the liver.


“3D InSight™ Human Liver Microtissues are engineered to reflect the complex multicellular composition and function of human liver for up to 4 weeks in culture. Unlike traditional 2D and simple 3D monoculture models, our microtissues can capture immune responses of the liver as well as effects of toxins on basic liver function,” said co-author Dr. Wolfgang Moritz, InSphero Head of External Collaborations and IP. 3D InSight™ Human Liver Microtissues are produced from multi-donor primary hepatocytes in co-culture with Kupffer cells and liver endothelial cells, the three liver cell types that cooperate in eliminating toxins and particulates from the body.


Heriot-Watt Research Toxicologist Dr. Ali Kermanizadeh added, “The presented data confirm that InSphero‘s human liver microtissues are more suitable for hazard assessment in response to chronic ENM exposure, given particularly by their longevity and immune-competence provided by the inclusion of Kupffer cells.”


The PATROLS project coordinator, Professor Shareen H. Doak from Swansea University said, “This research illustrates the value of using 3D primary human liver microtissue models to provide a better understanding of nanomaterial safety. A key focus of the PATROLS project is development of more-realistic, next-generation culture systems that allow us to move away from the need to test nanomaterials in animals. This paper is a great example of how PATROLS is making significant progress in this area.”


Read the Nature Scientific Reports paper “The importance of inter-individual Kupffer cell variability in the governance of hepatic toxicity in a 3D primary human liver microtissue model”


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