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The Humane Research Trust is funding a research project to advance liver toxicity research. Researchers at the University of Manchester are developing innovative hydrogels to help them grow liver cells in the lab. They hope this technology will optimise liver toxicity drug tests, reducing the use of animals and animal products.
The liver is one of the most critical and largest organs of the human body with a highly complex structure. It has several essential functions, from metabolising carbohydrates, lipids, toxins and drugs, to synthesising proteins and storing vitamins and glycogen.
Researchers must carefully consider potential liver toxicity when they develop new drugs or testing existing ones. Drugs can cause damage to the liver, known as ‘hepatic injury.’ Hepatic injury can lead to liver failure, which is often a life-threatening condition. When testing drugs, researchers must ensure it will not cause hepatic injury. This can result in delays to the drug approvals process.
“There are two clear overarching reasons that drugs do not make it to the clinic," said Professor Julie Gough, Professor of Biomaterials and Tissue Engineering at the University of Manchester. "Either they fail to work as intended, or they are simply not safe." This issue is becoming increasingly important, with liver diseases on the rise. In addition, this issue is compounded by the high cost of therapy and a lack of liver donors.
The Humane Research Trust is currently funding a liver research project at the University of Manchester. The project is led by Prof Gough, who is using entirely non-animal methodologies and products. At present, there is a global heavy reliance on animal testing within drug toxicity research. One common way of testing the hepatic toxicity of drugs uses a substance called Matrigel. Matrigel, derived from tumours grown in mice, is commonly used as a medium to grow liver cells in the lab.
Prof Gough and her research group are using hydrogels as an alternative to Matrigel. They have developed hydrogels from aminos acids, the building blocks of proteins in our body. This unique medium is effective at mimicking the extracellular matrix. The researchers want to identify the most optimal hydrogel to grow human liver cells in the lab. This would enable scientists to use these cells in experiments to test the toxicity of drugs or toxins.
“These hydrogel mimics of liver tissue could reduce the number of animals required for research. This is because they could enable decision-making prior to animal-model investigation,” said Prof Gough. “This would thereby reduce the number of animals used in drug-testing experiments.”
