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FRAME supports cell model research for NAFLD

The FRAME Alternatives Laboratory has recently been involved in a conference paper in Proceedings of the Nutrition Society, which looked at identifying the best cell models for studying non-alcoholic fatty liver disease (NAFLD).

The FRAME Alternatives Laboratory (FAL) supports many projects that aim to improve human health through research using human tissue. In this area, in-vivo animal models have previously been used or cell lines produced from animals, often rats. For some research, animal derived cell lines may still be the best ‘replacement’ option available. However, we know in some cases animal models cannot effectively replicate the effects of a disease, or successfully predict responses to drugs within the human body.  In the same way, some animal-derived cell lines are poor predictors of human cell reactions. To get the best scientific outcomes the most suitable available model should be used.

For many years, the FAL has been growing liver cells and fine-tuning culture techniques to replicate conditions in the human body.

The liver is responsible for the majority of metabolism of drugs and chemicals that enter the body. Creating accurate in-vitro liver models is therefore important in advancing non-animal methods in the field of drug discovery and toxicology. Liver disease is another area of research interest for the FAL. The global obesity epidemic has led to a huge increase in the incidence of non-alcoholic fatty liver disease (NAFLD, 25% of the UK population). NAFLD begins with the hepatic accumulation of lipid droplets within the liver cells (hepatocytes). This process is also known as hepatic steatosis.

Rodent models and cell lines are commonly used as models of the human liver but lack vital characteristics of the human organ. Primary human hepatocytes, derived from donated human liver samples, are the gold standard and are grown routinely in the FAL. Supply of primary human cells, however, is very limited and will never meet the needs of industry and academia.

Human liver cell models

As part of this research, the FAL has been involved in a recently published conference paper in Proceedings of the Nutrition Society, which compared primary human hepatocytes and HepG2 cells as models to study the development of hepatic steatosis. 1

To help identify better dietary recommendations, treatments and prevention strategies for NAFLD, there needs to be a greater understanding of the impact of specific nutrients on the liver and NAFLD development. This study compared the commonly used HepG2 hepatoma cell line, with primary human hepatocytes obtained from 3 patients undergoing elective liver surgery.

The study found differences between the behaviour of HepG2 cells and primary human hepatocytes when treated with different nutrients. They responded differently in terms of lipid accumulation and to glucose and fructose treatments, although had similar responses to fatty acid treatment. Here, both cells showed increased intracellular lipid, although more in the HepG2 cells. The study concluded that HepG2 cells may not therefore be a physiologically relevant model for studying NAFLD.

New, reproducible and sustainable models of human hepatocytes need to be developed to meet the pressing demand for human liver cell models.

  1. Hugget Z.J., Brameld J.M., Bennett A.J., Salter A.M. (2019). Comparison of primary human hepatocytes and HepG2 cells as models to study the development of hepatic steatosis. Proceedings of the Nutrition Society 78 (OCE1), E14

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