Liver xeno-repopulation with human hepatocytes in Fah-/-Rag2-/- mice after pharmacological immunosuppression.

The American Journal of Pathology
Zhiying HeXin Wang

Abstract

Functional human hepatocytes xeno-engrafted in mouse liver can be used as a model system to study hepatitis virus infection and vaccine efficacy. Significant liver xeno-repopulation has been reported in two kinds of genetically modified mice that have both immune deficiency and liver injury-induced donor hepatocyte selection: the uPA/SCID mice and Fah(-/-) Rag2(-/-)Il2rg(-/-) mice. The lack of hardy breeding and the overly elaborated technique in these two models may hinder the potential future application of these models to hepatitis virus infection and vaccination studies. Improving the transplantation protocol for liver xeno-repopulation from human hepatocytes will increase the model efficiency and application. In this study, we successfully apply immunosuppressive drug treatments of anti-asialo GM1 and FK506 in Fah(-/-)Rag2(-/-) mice, resulting in significant liver xeno-repopulation from human hepatocytes and human fetal liver cells. This methodology decreases the risk of animal mortality during breeding and surgery. When infected with hepatitis B virus (HBV) sera, Fah(-/-)Rag2(-/-) mice with liver xeno-repopulation from human hepatocytes accumulate significant levels of HBV DNA and HBV proteins. Our new protocol for humani...Continue Reading

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Citations

May 24, 2014·Cell Death & Disease·D XiangY-P Hu
Aug 28, 2013·Expert Opinion on Drug Metabolism & Toxicology·Katsutoshi Yoshizato, Chise Tateno
May 1, 2013·Current Opinion in Immunology·Ramesh Akkina
Jan 18, 2012·The International Journal of Biochemistry & Cell Biology·Zhi-Ying HeXin Wang
Mar 19, 2011·Science China. Life Sciences·Baoliang SuYiping Hu
Apr 9, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Min-Jun WangYi-Ping Hu
Oct 22, 2013·Biochemical and Biophysical Research Communications·Keiichi KosakaKazuaki Chayama
Nov 10, 2013·The American Journal of Pathology·Tanuja L GuttiLarisa Y Poluektova
Feb 27, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Fang YanYunfang Wang
Nov 29, 2017·Cellular and Molecular Life Sciences : CMLS·Salamah M AlwahshDavid C Hay
Jul 17, 2019·Inflammation and Regeneration·Tomoko YamaguchiTakahiro Ochiya
Apr 4, 2021·Viruses·Katja Giersch, Maura Dandri

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