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Revolutionising drug safety: Growing game-changing human liver cells

Professor Kenneth Linton

Professor Kenneth Linton

Queen Mary University London

Animals to be replaced: Mice, rats, guinea pigs and rabbits

At Queen Mary University London, Professor Kenneth Linton’s main area of research is the study of proteins that move things in and out cells, known as transporters, and their functions including the movement and flow of bile from the liver. This new project focuses on the role of transporters in liver cells to understand their role in the development of drug induced liver injury.

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The Problem – Drug Induced Liver Injury

Millions of animals are used each year worldwide for the safety testing of drugs and other substances.

The liver makes a fluid called bile, which helps break down fats during digestion and carries waste products out of the liver into the digestive tract, where they leave the body. Proteins known as transporters act as conveyor belts to move the bile and processed drugs out of the liver into the gut. Sometimes drugs mistakenly target these transporters, which can cause drug induced liver injury (DILI).

Although drugs are tested in animals before they are approved for use in humans, DILI is still a common and serious problem which can result in patient deaths. This is because there are important differences in the chemical makeup of human and animal bile fluid and in its production.

To avoid this problem and replace the use of animals in drug development, human liver cells can be used for drug safety testing in the lab. However, when grown for long periods of time, liver cells can lose or undergo changes in their unique characteristics, including their ability to make bile. This could make the results unreliable, putting patients at risk.

A better liver model

To overcome this problem, Professor Kenneth Linton at Queen Mary University of London has developed a new way to make liver cells from human-derived stem cells (special cells which can develop into many different cell types). These cells are able to keep their characteristics and most importantly, keep their bile-making abilities when grown in the lab. If scaled up, this technique could provide a limitless supply of cells for drug testing, replacing animals in experiments.

Professor Linton is currently growing these liver cells using a gel-like scaffold system for the cells to grow on called Matrigel, which is made using animal ingredients. Over the course of this Animal Free Research UK funded 12-month pilot project, he will replace these Matrigel structures with an animal-free alternative to allow drug testing on the liver cells without the use of any animal-derived products.

Training the next generation

Over the course of the project, two early career researchers will be trained in these techniques (one masters student and a final year undergraduate Biomedical Scientist). Professor Linton is also preparing two papers for publication and will share the results on his lab webpage, through presentations and through his relationships with industry partners, which will help other scientists to learn about and use the technology. In the future he also plans to apply for further funding to grow this technology and implement its use in standard drug development and testing practices.

Millions of animals are used each year worldwide for the safety testing of drugs and other substances, most of which are mice and rats. The use of these liver cells for drug safety testing could replace animals used in these experiments while gaining human-relevant results, leading to safer and more effective treatments for patients.