Diagnosis for hepatitis, development of a vaccine for hepatitis virus and development of a new drug for liver diseases using primary culture of human hepatocytes

点击翻译按钮获取中文摘要

Adult rat hepatocytes in primary culture maintain many liver functions and respond to various hormones in the same ways as hepatocytes do in vivo. Moreover, mature hepatocyes can proliferate in vitro when cultured at low cell density with growth factors such as EGF and hepatocyte growth factor(HGF). Recently, we showsthat C <Cl_4> at low concentrations causes enzyme leakage from cultured adult rat hepatocytes due to a change in the permeability of the cell membrane and also demonstrate that glycyrrhyzin and glucocorticoid has a protective effect on enzyme leakage from the cell induced by C <Cl_4> . Thus, primary cultures of adult rat hepatocytes are a useful for toxicology and development of a new drug for liver disease. However, although these findings with rat hepatocytes must be very useful in understanding human hepatology, they cannot be applied to human liver directly. Therefore, it is necessary to study human hepatocytes in primary culture in comparison with those of rat liver. In particular, since human hepatitis virus has strict species specificity, it is essential to use human hepatocytes to study this virau infection, especially for the identification for non-A, non-B hepatitis virus. Hepatocytes were isolated from liver biopsy specimens and cultured in serum-free medium as monolayers. We found that proliferation of human hepatocytes can be induced by insulin EGF and HGF, and that growth of hepatocytes suppressed that of non-parenchymal liver cells in co-culture. Primary cultures of human hepatocytes are useful for diagnosis, identification and development of a vaccine for non-A, non-B hepatitis virus.