Researchers have created the first artificial human liver model from genetically engineered human liver cells. It is hoped that the artificial liver will be an effective model to study fatty liver diseases.

Non-alcoholic fatty liver disease (NAFLD) is a condition where fat builds up in the liver, eventually leading to liver failure. There is currently no cure for NAFLD both because of the disease complexity and lack of biological models. Due to the differences between mice and human liver physiology NAFLD is difficult to study in mice, so there is a need for an effective human liver model.

The gene SIRT1 has been shown to impact the development of NAFLD due to its role in liver energy metabolism. Although the expression of SRTT1 has been shown to be lower in patients with NAFLD, SRTT1 protein targeted therapies have had inconclusive results in clinical trials.

In this study, human liver cells were extracted from a donor and had their SRT1 expression knocked down. The cells were then converted into pluripotent stem cells and then re-differentiated into human liver cells.

The liver cells were assembled on a rat liver stripped of all its cells. They were able to self-assemble into a 3D fully-functional liver, with blood vessels and the usual structural features of a working liver.

Once formed, the liver displayed an accumulation of triglycerides, increased inflammation and macrovesicular steatosis, a build-up of fat vesicles within the cells. All features are characteristic of early fatty liver disease. The lack of expression of the SIRT1 gene was therefore shown to contribute directly to fatty liver formation.

The artificial liver therefore shows promise as both a model for NAFLD and a future artificial organ for use in humans.

Front Line Genomics recently partnered with WuXi NextCODE to produce the webinar New Approaches to the Old Hunt for NASH Therapies. The conversation was moderated by Donna Cryer, the President and CEO of the Global Liver Institute. The panel discussed why there has been limited progress in therapies for nonalcoholic steatohepatitis (NASH) and possible approaches for the future. The Webinar can be watched for free on demand here.