Disease Modelling of the Liver

Liver disease is a major health problem worldwide accounting for approximately 2 million deaths each year. It is the only cause of death that has continued to increase year on year since 1970. It is estimated that one in three people have been infected with Hepatitis B worldwide; furthermore, drug-induced liver damage is an increasing challenge for drug discovery.

Modelling NAFLD and NASH

One of the most common causes of chronic liver disease worldwide is Non-Alcoholic Fatty Liver Disease (NAFLD). NAFLD is a spectrum of metabolic diseases in which fat builds up in the liver in the absence of excess alcohol consumption. Non-Alcoholic Steatohepatitis (NASH) is the severest form on the NAFLD spectrum. Approximately twenty percent of people diagnosed with NAFLD go on to develop NASH, which is associated with steatosis, inflammation, presence of immune cells in the liver, and insulin resistance.

Left untreated, NASH may progress further into cirrhosis and/or liver cancer.

Modelling NAFLD and NASH

Our understanding of the molecular pathways underlying NAFLD/NASH progression has relied primarily on in vivo mouse models. However, none of the current mouse models displays the full spectrum of NASH pathophysiology.

CN Bio has developed hepatic in vitro models using the company’s 3D perfused platform, PhysioMimix™ . Using this platform, two assays have been developed for NAFLD/steatosis and NASH disease states, both of which are available for license.

In vitro NAFLD/NASH models

The NAFLD/steatosis model contains primary human hepatocytes loaded with free fatty acids to induce hepatic steatosis and metabolic changes.

The NASH model contains Kupffer cells and human stellate cells. Fat loading causes activation of human stellate cells, leading to inflammatory responses and expression of extracellular fibrotic proteins.

The models can be used to screen potential therapies against NAFLD/steatosis and NASH. They can also be used to investigate the molecular pathways underlying these processes and the metabolic properties of hepatocytes under disease conditions.

License the NASH Protocol

For Notable publications in disease modelling visit our Publications page

Preclinical tool for studying Hepatitis B infection

There are more than 240 million people infected with Hepatitis B (HBV) worldwide. Infection is associated with the development of liver cirrhosis and hepatocellular carcinoma. The study of HBV is complicated by the lack of suitable in vitro models that allow all steps of the viral life cycle or viral interaction with the host to be recapitulated. High viral titres are necessary to initiate infection in most in vitro culture models.

The inability to mimic the complexity of the liver using cell lines and regular primary human hepatocyte culture poses significant limitations for studying host/pathogen interactions.

In vitro models for studying Hepatitis B

CN Bio has developed perfused 3D liver cultures as a physiological preclinical tool to study HBV life cycle in the human liver. Primary human hepatocytes cultured in 3D in our Liver-on-Chip system are permissive to HBV infection and can be maintained for at least 40 days, enabling the recapitulation of all steps of the HBV life cycle.

The innate immune and cytokine responses following HBV infection in this in vitro microphysiological system mimic those observed in HBV-infected patients, creating an ideal tool for modelling the disease.

The co-culture of primary human hepatocytes and non-parenchymal cells in this system provides a valuable preclinical platform for HBV research.

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