PROPAGATION OF HUMAN HEPATOCYTES IN NON-HUMAN ANIMALS

摘要

The present invention relates to the preparation of non-human animals having chimeric livers, whereby some or substantially all of the hepatocytes present are human hepatocytes. It is based, at least in part, on the discovery that rats, tolerized in utero against human hepatocytes, were found to serve as long-term hosts for human hepatocytes introduced post-natally, and the introduced hepatocytes maintained their differentiated phenotype, as evidenced by continued production of human albumin. The present invention further relates to the use of such animals as models of various liver diseases, including viral invention. Such embodiments are based on the discovery that transplanted human hepatocytes in chemeric livers were found to be susceptible to HBV infection in situ and supported replication of the virus as evidenced by the appearance of HBsAg in serum and in liver cells and by the presence of covalently closed circular DNA forms in liver.