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Semin Liver Dis 2020; 40(02): 189-212
DOI: 10.1055/s-0040-1701444
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Art of Making Artificial Liver: Depicting Human Liver Biology and Diseases in Mice

Go Sugahara
1   Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California
2   Research & Development Department, PhoenixBio, Co., Ltd, Higashi-Hiroshima, Hiroshima, Japan
,
Yuji Ishida
1   Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California
2   Research & Development Department, PhoenixBio, Co., Ltd, Higashi-Hiroshima, Hiroshima, Japan
,
Jeffrey Sun
1   Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California
,
Chise Tateno
2   Research & Development Department, PhoenixBio, Co., Ltd, Higashi-Hiroshima, Hiroshima, Japan
,
Takeshi Saito
1   Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California
3   USC Research Center for Liver Diseases, Los Angeles, California
› Author Affiliations
Financial Support This work was supported by funds from NIH NIAAA (R21AA022751: TS), NIH NIAID (R21AI139954: TS), NIH NIDDK (RO1DK101773: TS), and research funding from PhoenixBio.
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Publication History

Publication Date:
19 February 2020 (online)

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Abstract

Advancement in both bioengineering and cell biology of the liver led to the establishment of the first-generation humanized liver chimeric mouse (HLCM) model in 2001. The HLCM system was initially developed to satisfy the necessity for a convenient and physiologically representative small animal model for studies of hepatitis B virus and hepatitis C virus infection. Over the last two decades, the HLCM system has substantially evolved in quality, production capacity, and utility, thereby growing its versatility beyond the study of viral hepatitis. Hence, it has been increasingly employed for a variety of applications including, but not limited to, the investigation of drug metabolism and pharmacokinetics and stem cell biology. To date, more than a dozen distinctive HLCM systems have been established, and each model system has similarities as well as unique characteristics, which are often perplexing for end-users. Thus, this review aims to summarize the history, evolution, advantages, and pitfalls of each model system with the goal of providing comprehensive information that is necessary for researchers to implement the ideal HLCM system for their purposes. Furthermore, this review article summarizes the contribution of HLCM and its derivatives to our mechanistic understanding of various human liver diseases, its potential for novel applications, and its current limitations.

Keywords

humanized liver chimeric mouse - human hepatocyte - liver diseases - liver biology - bioengineering