The liver plays a critical role in vertebrate biology. It has many important metabolic functions, including the regulation of glucose and cholesterol metabolism, the production of plasma proteins including clotting factors, and the detoxification of endogenous and exogenous compounds. The liver also produces various hormones involved in insulin regulation, blood pressure, and blood lipid levels. Because of the many physiological processes that depend on the liver, a fundamental understanding of liver biology and the ability to address these at the benchtop is essential for researchers involved in creating new, life-saving medicines.
The liver is composed of five major cell types. Hepatocytes comprise approximately 70% of the liver cell population and are responsible for most metabolic and hormonal processes. The other four cell types, collectively known as hepatic non-parenchymal cells, consist of resident macrophages called Kupffer cells, stellate cells, liver sinusoidal endothelial cells, and cholangiocytes. These cells serve to support the liver structure, transport molecules in and out, and communicate with the immune system.
One of the greatest challenges in drug development is the prediction of the safety and the metabolic fate of a new drug before it enters human clinical trials. Because the liver is the major site of metabolism and detoxification, in vitro cell systems that mimic the liver are significantly useful for predicting the consequences of drugs administered to humans in the clinic. The ability to isolate highly pure hepatocyte populations from non-transplantable, donated human livers to mimic the human liver environment has therefore become an integral part of the drug development pipeline.