3D人类肝脏类器官：研究HBV感染，复制和肝肿瘤发生的体外平

StephenW

3D human liver organoids: An in vitro platform to investigate HBV infection, replication and liver tumorigenesis
Shringar Rao  1 , Tanvir Hossain  1 , Tokameh Mahmoudi  2
Affiliations
Affiliations

    1
    Department of Biochemistry, Erasmus University Medical Centre, PO Box 2040, 3000, CA, 9 Rotterdam, the Netherlands.
    2
    Department of Biochemistry, Erasmus University Medical Centre, PO Box 2040, 3000, CA, 9 Rotterdam, the Netherlands. Electronic address: [email protected].

    PMID: 33675983 DOI: 10.1016/j.canlet.2021.02.024

Abstract

Hepatitis B Virus (HBV) infection is a leading cause of chronic liver cirrhosis and hepatocellular carcinoma (HCC) with an estimated 400 million people infected worldwide. The precise molecular mechanisms underlying HBV replication and tumorigenesis have remained largely uncharacterized due to the lack of a primary cell model to study HBV, a virus that exhibits stringent host species and cell-type specificity. Organoid technology has recently emerged as a powerful tool to investigate human diseases in a primary 3D cell-culture system that maintains the organisation and functionality of the tissue of origin. In this review, we describe the utilisation of human liver organoid platforms to study HBV. We first present the different categories of liver organoids and their demonstrated ability to support the complete HBV replication cycle. We then discuss the potential applications of liver organoids in investigating HBV infection and replication, related tumorigenesis and novel HBV-directed therapies. Liver organoids can be genetically modified, patient-derived, expanded and biobanked, thereby serving as a clinically-relevant, human, primary cell-derived platform to investigate HBV. Finally, we provide insights into the future applications of this powerful technology in the context of HBV-infection and HCC.

Keywords: Disease modelling; Hepatitis B Virus; Hepatocellular carcinoma; Liver organoids.

Copyright © 2021. Published by Elsevier B.V.

StephenW

3D人类肝脏类器官：研究HBV感染，复制和肝肿瘤发生的体外平台
Shringar Rao 1，Tanvir Hossain 1，Tokameh Mahmoudi 2
隶属关系
隶属关系

    1个
    伊拉斯姆斯大学医学中心生物化学系，荷兰鹿特丹9号邮政信箱2040，3000，CA。
    2个
    伊拉斯姆斯大学医学中心生物化学系，荷兰鹿特丹9号邮政信箱2040，3000，CA。电子地址：[email protected]。

    PMID：33675983 DOI：10.1016 / j.canlet.2021.02.024

抽象的

乙型肝炎病毒（HBV）感染是慢性肝硬化和肝细胞癌（HCC）的主要原因，全世界估计有4亿人被感染。由于缺乏研究HBV的原代细胞模型，HBV复制和肿瘤发生的确切分子机制在很大程度上尚未表征，HBV是一种表现出严格宿主种类和细胞类型特异性的病毒。最近，有机体技术已成为一种强大的工具，可以在维持原始组织的组织和功能的主要3D细胞培养系统中研究人类疾病。在这篇综述中，我们描述了利用人类肝类器官平台来研究HBV。我们首先介绍了不同类别的肝脏类器官及其支持完整HBV复制周期的已证明能力。然后，我们讨论肝脏类器官在研究HBV感染和复制，相关的肿瘤发生和新的HBV定向疗法中的潜在应用。可以对肝类器官进行基因修饰，患者衍生，扩增和生物储存，从而成为临床相关的人类原代细胞来源平台，用于研究HBV。最后，我们对HBV感染和HCC背景下这一强大技术的未来应用提供了见解。

关键字：疾病建模；乙型肝炎病毒;肝细胞癌；肝类器官。

版权所有©2021，由Elsevier B.V.发布。