Toxicity Studies in Organoid Models: Developing an Alternative to Animal Testing

Alternatives to animal testing have long been explored when it comes to studying the safety of various chemical compounds for use in food, medicine and cosmetics. With the advent of three-dimensional (3D) cell culture to create organoids, more relevant human organoid models are being explored as one way to provide safe and effective compound testing while minimizing the need for testing in animals. The international project Physiologically Anchored Tools for Realistic nanOmateriaL hazard aSsessment (PATROLS) led by the Swansea University Medical School aims to establish a battery of innovative, next-generation safety testing tools that can more accurately predict the effects of engineered nanomaterial (ENM) exposure in humans and the environment.

One project being researched by Samantha Llewellyn, a research assistant at Swansea University, is developing predictive physiologically relevant 3D liver models for ENM safety assessment. By having a model to evaluate realistic ENM exposures, a researcher can study liver function, hepatic metabolism and microtissue cell viability after acute (24 hours) or prolonged (several days) exposure. A microtissue model for assessing ENM hepatotoxicity needs to mimic primary hepatocytes and be amenable to assays used to test cell viability and metabolism.

The right tools for testing this 3D liver model include the bioluminescent-based CellTiter-Glo® 3D Viability and P450-Glo® Assays. When creating organoids, having reagents that can penetrate to the center of the dense and complex 3D liver spheroids is important so that the cell viability readout encompasses the entire microtissue. The CellTiter-Glo® 3D Viability Assay accomplishes this task, providing accurate assessment of 3D tissue cell health. Measuring cytochrome P450 (CYP450) activity is necessary for studying liver function. The P450-Glo® Assays have the flexibility to assess CYP450 activity while preserving the liver spheroids; thus, researchers can gather more data from a single experiment.

The importance of Samantha Llewellyn’s research as part of PATROLs is establishing a 3D liver model that could evaluate realistic ENM exposures and reduce the need for animal testing. Bioluminescent assays for assessing cell health and liver enzyme function are necessary to reach this goal.

luciferse technologies are allowing researchers to develop predictive 3D organoid models for ERM testing

To learn more about the last 30 years of bioluminescent innovations and the discoveries they’ve enabled, please visit our 30th anniversary celebration page.

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Sara is a native Wisconsinite who grew up on a fifth-generation dairy farm and decided she wanted to be a scientist at age 12. She was educated at the University of Wisconsin—Parkside, where she earned a B.S. in Biology and a Master’s degree in Molecular Biology before earning her second Master’s degree in Oncology at the University of Wisconsin—Madison. She has worked for Promega Corporation for more than 15 years, first as a Technical Services Scientist, currently as a Technical Writer. Sara enjoys talking about her flock of entertaining chickens and tries not to be too ambitious when planning her spring garden.

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