体外原代人肝细胞的长期功能维持

StephenW

Long-term functional maintenance of primary human hepatocytes in vitro

    Chengang Xiang1,*, Yuanyuan Du1,*, Gaofan Meng1,*, Liew Soon Yi1, Shicheng Sun1, Nan Song1, Xiaonan Zhang2, Yiwei Xiao3, Jie Wang3, Zhigang Yi4, Yifang Liu5, Bingqing Xie6, Min Wu2, Jun Shu4, Da Sun6, Jun Jia1, Zhen Liang6, Dong Sun1, Yanxiang Huang7, Yan Shi1, Jun Xu1, Fengmin Lu3, Cheng Li5, Kuanhui Xiang3, Zhenghong Yuan4,†, Shichun Lu8,†, Hongkui Deng1,6,†

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Science  26 Apr 2019:
Vol. 364, Issue 6438, pp. 399-402
DOI: 10.1126/science.aau7307

  

Keep hepatocytes fresh

Freshly isolated primary human hepatocytes (PHHs) quickly lose their identity and function in vitro, limiting their application in modeling infectious liver diseases and screening drugs. Xiang et al. describe a simple and effective five-chemical culture condition that can maintain the mature function of cultured PHHs for an extended period of time. PHHs cultured in this way can support the entire viral life cycle and recapitulate long-term infection of the hepatitis B virus. This system created a useful drug-screening platform for developing new antiviral strategies.

Science, this issue p. 399
Abstract

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.

StephenW

体外原代人肝细胞的长期功能维持

    Chengang Xiang1，*，Yuanyuan Du1，*，Gaofan Meng1，*，Liew Soon Yi1，Shicheng Sun1，Nan Song1，Zhangananan Zhang2，Yiwei Xiao3，Jie Wang3，Zhigang Yi4，Liu Yifang Liu，Bingqing Xie6，Min Wu2，Jun Shu4，Da Sun6，Jun Jia1，Zhen Liang6，Dong Sun1，Yanxiang Huang7，Yan Shi1，Jun Xu1，Fengmin Lu3，Cheng Li5，Kuanhui Xiang3，Zhenghong Yuan4，†，Shichun Lu8，†，Hongkui Deng1,6，†

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科学26四月2019：
卷。 364，Issue 6438，pp.399-402
DOI：10.1126 / science.aau7307

  

保持肝细胞新鲜

新鲜分离的原代人肝细胞（PHH）在体外迅速丧失其特性和功能，限制了它们在模拟感染性肝病和筛选药物中的应用。翔等人。描述了一种简单有效的五化学培养条件，可以长时间保持培养的PHH的成熟功能。以这种方式培养的PHH可以支持整个病毒生命周期并重现乙型肝炎病毒的长期感染。该系统为开发新的抗病毒策略创建了一个有用的药物筛选平台。

科学，这个问题p。 399
抽象

在体外维持终末分化细胞，尤其是肝细胞已被证明具有挑战性。在这里，我们通过使用五种化学物质（5C）的组合调节细胞信号传导途径，证明了原代人肝细胞（PHH）的长期体外维持。 5C培养的PHH显示全局基因表达谱和肝细胞特异性功能，类似于新鲜分离的对应物。此外，这些细胞在4周内有效地重现乙型肝炎病毒（HBV）感染的整个过程，产生感染性病毒颗粒并形成HBV共价闭合的环状DNA。我们的研究表明，通过化学方法，PHH的功能性维持支持体外长期HBV感染，为研究HBV细胞生物学和抗病毒药物筛选提供了有效的平台。