Humanized Murine Model for HBV and HCV Using Human Induced Pluripotent Stem Cells

Infection of hepatitis B virus (HBV) and hepatitis C virus (HCV) results in heterogeneous outcomes from acute asymptomatic infection to chronic infection leading to cirrhosis and hepatocellular carcinoma (HCC). In vitro models using animal hepatocytes, human HCC cell lines, or in vivo transgenic mouse models have contributed invaluably to understanding the pathogenesis of HBV and HCV. A humanized mouse model made by reconstitution of human primary hepatocytes in the liver of the immunodeficient mouse provides a novel experimental opportunity which mimics the in vivo growth of the human hepatocytes. The limited access to primary human hepatocytes necessitated the search for other cellular sources, such as pluripotent stem cells. Human embryonic stem cells (hESCs) have the features of self-renewal and pluripotency and differentiate into cells of all three germ layers, including hepatocytes. Humaninduced pluripotent stem cells (iPSCs) derived from the patient's or individual's own cells provide a novel opportunity to generate hepatocyte-like cells with the defined genetic composition. Here, we will review the current perspective of the models used for HBV and HCV study, and introduce the personalized mouse model using human iPSCs. This novel mouse model will facilitate the direct investigation of HBV and HCV in human hepatocytes as well as probing the genetic influence on the susceptibility of hepatocytes to HBV and HCV.