Modelling Disease States In Primary Human Cells

Much of the research carried out in order to understand the basis of common human diseases relies on rodent models and the use of animal tissue. While such studies can be informative, there is currently a lack of good model systems based on human cells in vitro.

The FAL (FRAME ALternatives Laboratory) conducts research aimed at producing models of disease related to obesity and obesity related-diabetes using primary human cells. Such research is vitally important given the epidemic of obesity in the Western and developing worlds and the subsequent use of large numbers of animals in the search for answers to the health problems caused by obesity and diabetes.

Using human hepatocytes and stellate cells, we are currently developing models of fatty liver disease and non-alcoholic steatohepatitis – diseases that were rare until recently but which are now common and a major cause of morbidity and mortality.

We use co-culture of stellate cells and hepatocytes to recreate human fatty liver disease using a variety of methods including incubation with purified human lipoprotein fractions to induce lipid deposition in cultured cells. Biochemical and gene expression analysis is then used to assess the effects of lipid loading in human cells.

A similar technique is used to induce insulin resistance in primary human skeletal muscle myotubes as a model for obesity induced diabetes.