Immunodeficient mice are transplanted via splenic injection with isolated human hepatocytes taken from noninfected human donors. The transplanted cells translocate to and engraft within the mouse’s liver.
Human hepatocytes repopulate the mouse liver in an organized fashion and retain long term normal pharmacological responses. Human hepatocytes in the mouse liver are functional and secrete a variety of hepatic proteins. The replacement of mouse hepatocytes with human hepatocytes generally correlates with human albumin (hAlb) levels.
Upon engraftment, the PXB-mice with humanized liver can be inoculated with human serum containing infectious viral particles (HCV, HBV) and they support durable replication of the virus at levels observed in humans. The model provides an authentic viral infection utilizing human liver cells infected with virus (or malaria parasite) in a true in vivo settings.The non-infected PXB–mice can be utilized to address early evaluation of toxicity in human hepatocytes and characterization of human-type drug and lipoprotein metabolism. These applications are beneficial for safety assessm
ent and DMPK studies.