Hepatitis viral infections, both HCV and HBV, remain common diseases in both the developing and developed worlds. These infections can lead to liver damage manifesting as fibrotic and cirrhotic liver tissue and can result in the need for liver transplantation. To date, cell-based models of HCV and HBV infection and the viral replication cycle have been limited.
In recent studies, we have observed the presence of markers required to afford HCV attachment to, and uptake by, iPSC-differentiated hepatocytes (Figure 3). iCell Hepatocytes have been observed to exhibit SR-B1 and CD81 proteins, which are required for viral attachment. In addition, the cells stain positively for Occludin and Claudin1, which are required for viral internalization within the cell.
The data shown demonstrate that iCell Hepatocytes are capable of HCV uptake as evidenced by the staining with a luciferase-tagged viral particle. Notably, virus uptake is inhibited in a dose-dependent fashion by the anti-CD81 blocking antibody. The use of human iPSC-derived hepatocytes for the study of HCV activity, as well as for the identification of novel therapeutics to prevent viral injury, are thus enabled by this system.
In summary, CDI’s iCell Hepatocytes are a predictive in vitro model system for the study of hepatotoxicity and metabolic function as well as disease modeling, including HCV studies. These human iPSC-derived hepatocytes provide an improvement over existing models by delivering a consistent, reproducible, and limitless source of liver tissue that is reflective of native human liver function.