用功能性人类免疫系统和肝细胞重建的下一代人源化小鼠能

StephenW

用功能性人类免疫系统和肝细胞重建的下一代人源化小鼠能否模拟病毒性肝炎向肝癌发生的进展？
郭晶龙 1 , 王思月 2 , 齐高 1
隶属关系
隶属关系

    1
    【作者单位】： 吉林大学第一医院心血管内科;
    2
    美国德克萨斯州休斯顿贝勒广场一号贝勒医学院免疫学和微生物学研究生课程。

    PMID：36213658 PMCID：PMC9537463 DOI：10.3389/fmed.2022.1002260

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抽象的

乙型肝炎病毒 (HBV) 和丙型肝炎病毒 (HCV) 慢性感染会导致肝炎、纤维化、肝硬化和肝细胞癌等肝脏免疫病理学疾病，这些疾病难以治疗并继续成为全球主要的健康问题。由于 HBV 和 HCV 的物种特异性嗜肝性，传统啮齿动物模型在研究感染和相关肝脏免疫发病机制方面的效用受到限制。用功能性人类免疫系统和肝细胞重建的人源化小鼠（HIS-HuHEP 小鼠）对于 HBV 或 HCV 感染的体内研究以及肝脏免疫发病机制进展的人类特异性方面非常有用。然而，目前的 HIS-HuHEP 小鼠都不能模拟病毒性肝炎向肝癌发生的进展，这可能是患者 HBV 或 HCV 慢性感染的一个臭名昭著的结果，这表明它们在功能上受到损害，并且仍有很大的改进空间和建立功能更完善的下一代HIS-HuHEP小鼠。在这篇综述中，我们首先总结了建立 HIS-HuHEP 小鼠的主要要求。然后，我们讨论了当前 HIS-HuHEP 小鼠及其应用的各自协议，以及它们的优缺点。我们还提出了进一步改进和建立下一代 HIS-HuHEP 小鼠的观点。

关键词：肝硬化；纤维化;肝炎病毒；肝细胞癌;人肝细胞嵌合体；人性化免疫系统；人源化小鼠；肝脏免疫发病机制。

版权所有 © 2022 郭、王和高。
利益冲突声明

作者声明，该研究是在没有任何可能被解释为潜在利益冲突的商业或财务关系的情况下进行的。处理编辑 ZH 在审查时宣布与作者 QG 和 JG 共享隶属关系。

StephenW

Can next-generation humanized mice that reconstituted with both functional human immune system and hepatocytes model the progression of viral hepatitis to hepatocarcinogenesis?
Jinglong Guo  1 , Siyue Wang  2 , Qi Gao  1
Affiliations
Affiliations

    1
    Department of Cardiovascular Disease, The First Hospital of Jilin University, Changchun, China.
    2
    Graduate Program in Immunology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, United States.

    PMID: 36213658 PMCID: PMC9537463 DOI: 10.3389/fmed.2022.1002260

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Abstract

Hepatitis B virus (HBV) and Hepatitis C virus (HCV) chronic infections cause liver immunopathological diseases such as hepatitis, fibrosis, cirrhosis, and hepatocellular carcinomas, which are difficult to treat and continue to be major health problems globally. Due to the species-specific hepato-tropism of HBV and HCV, conventional rodent models are limited in their utility for studying the infection and associated liver immunopathogenesis. Humanized mice reconstituted with both functional human immune system and hepatocytes (HIS-HuHEP mice) have been extremely instrumental for in vivo studies of HBV or HCV infection and human-specific aspects of the progression of liver immunopathogenesis. However, none of the current HIS-HuHEP mice can model the progression of viral hepatitis to hepatocarcinogenesis which may be a notorious result of HBV or HCV chronic infection in patients, suggesting that they were functionally compromised and that there is still significant space to improve and establish next-generation of HIS-HuHEP mice with more sophisticated functions. In this review, we first summarize the principal requirements to establish HIS-HuHEP mice. We then discuss the respective protocols for current HIS-HuHEP mice and their applications, as well as their advantages and disadvantages. We also raise perspectives for further improving and establishing next-generation HIS-HuHEP mice.

Keywords: cirrhosis; fibrosis; hepatitis virus; hepatocellular carcinoma; human hepatocytes chimeric; humanized immune system; humanized mice; liver immunopathogenesis.

Copyright © 2022 Guo, Wang and Gao.
Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling Editor ZH declared a shared affiliation with the authors QG and JG at the time of review.

StephenW

https://www.frontiersin.org/arti ... ed.2022.1002260/pdf