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FAL research: the liver

This year, the world-renowned FRAME Alternatives Laboratory (FAL) celebrates its 30-year anniversary. Funded by an annual grant made by FRAME to support its work, the FAL is based at the University of Nottingham Medical School and aims to produce human-based research systems for medical research that are better and more relevant to humans than current animal models.

The FAL’s current cutting-edge research is based around three key pillars: neuroinflammation, the liver and biomaterials. Here, we explain the FAL’s research into the liver and how its researchers use human cells to model liver disease.

The liver

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are two of the least well publicised health epidemics affecting the western world and are closely linked to obesity and Type 2 diabetes. The liver is an important focus of the FAL’s research as there are currently no available treatments for NAFLD and NASH.

In NAFLD, fat accumulates in the liver. Over time, this leads to inflammation and then fibrosis – scarring of the liver. To model this process, the FAL uses all the primary human cells involved in the liver, including hepatocyte cells, Kupffer cells, stellate cells and cells with liver disease (fibrosis), all derived from liver samples which are ethically sourced from hospitals in the East Midlands region.

As the liver has a remarkable capacity to regenerate, the FAL is also isolating the cells it believes are adult stem cells and is growing and differentiating these to produce hepatocytes. The FAL then produces ‘scaffolding’ from donated human liver tissue that has had the original cells removed. New cells (healthy or damaged) can be inserted by FAL researchers to produce mini organs that can be used to investigate liver diseases, toxicity and the effectiveness of potential drugs.