Long-term functional maintenance of primary human hepatocytes in vitro.
Chengang XiangYuanyuan DuGaofan MengLiew Soon YiShicheng SunNan SongXiao-Nan ZhangYiwei XiaoJie WangZhigang YiYifang LiuBingqing XieMin WuJun ShuDa SunJun JiaZhen LiangDong SunYanxiang HuangYan ShiJun XuFengmin LuCheng LiKuanhui XiangZhenghong YuanShi-Chun LuHongkui DengPublished in: Science (New York, N.Y.) (2019)
The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.
Keyphrases
- hepatitis b virus
- induced apoptosis
- endothelial cells
- liver failure
- signaling pathway
- cell cycle arrest
- liver injury
- single cell
- cell therapy
- induced pluripotent stem cells
- endoplasmic reticulum stress
- oxidative stress
- circulating tumor
- pluripotent stem cells
- pi k akt
- emergency department
- single molecule
- sars cov
- genome wide
- cell death
- transcription factor
- epithelial mesenchymal transition
- cell proliferation
- mesenchymal stem cells
- preterm birth
- adverse drug