While hepatitis B infection is preventable by a well-established vaccine, the disease has proven to be extremely difficult to cure once infection occurs. Unfortunately, advances in this area are hindered by a lack of easily accessible and physiologically relevant infection models for study. HUREL’s liver models confront this challenge head-on with the development of “micro livers” – self-assembling co-cultures of cryopreserved primary hepatocytes that can maintain persistent infection for more than 40 days’ time.
In 2017, HUREL scientists and colleagues in the Muir and Ploss labs at Princeton University published a report on their successful liver model in the journal Nature Communications. In this paper, “Long-term hepatitis B infection in a scalable hepatic co-culture system,” Winer et al. described the novel approach with an eye toward its use in high-throughput assays, including inhibition of viral entry and the efficacy of antivirals.
The global impact of hepatitis B cannot be overstated. It is highly infectious – amazingly, it is estimated that around one in three people around the globe have been infected by the hepatitis B virus. Of these, nearly 300 million live with chronic infections, putting them at risk of complications such as liver fibrosis, cirrhosis, and hepatocellular carcinoma. In fact, hepatitis B is the leading cause of liver cancer around the world, and more than 800,000 deaths in total are attributable to the virus each year.
A number of challenges have stepped in the way of progress toward understanding the mechanics of the virus in liver tissue. For example, liver cells from hepatoma cell lines are readily cultured, but their patterns of proliferation and gene regulation differ significantly from primary human hepatocytes (PHHs). When PHHs are used directly, however, culture conditions readily lead to the cells’ loss of hepatic function and overall dedifferentiation.
As outlined in the 2017 report, Visikol’s HUREL model micro livers overcome these traditional limitations with the innovation of co-culturing PHHs with stromal cells. This co-culture model is very flexible, not only maintaining infection for an extended period of time, but also proving amenable to infection by viruses obtained from both cell culture and hepatitis B patients. Additionally, the infection protocol can be carried out up to 15 days after plating the cells, opening up many opportunities for innovative experimental design.
Importantly, the HUREL micro liver platform is relevant for much more than studies of viral infection. Its suitability for analysis in 96-well plates enables many highly uniform replicates to be carried out in assessing everything from viral activity, to liver metabolism, to hepatotoxicity. HUREL micro livers play an important role in the Visikol portfolio of liver assay services, the most comprehensive suite in the marketplace for studying the liver in two or three dimensions, in vitro and/or ex vivo, and with a wide variety of endpoint offerings. Please feel free to contact our team of experts with any questions you may have regarding your liver assay needs.