TY - JOUR T1 - HBV infection-induced liver cirrhosis development in dual-humanised mice with human bone mesenchymal stem cell transplantation JF - Gut JO - Gut SP - 2044 LP - 2056 DO - 10.1136/gutjnl-2018-316091 VL - 68 IS - 11 AU - Lunzhi Yuan AU - Jing Jiang AU - Xuan Liu AU - Yali Zhang AU - Liang Zhang AU - Jiaojiao Xin AU - Kun Wu AU - Xiaoling Li AU - Jiali Cao AU - Xueran Guo AU - Dongyan Shi AU - ­Jun Li­ AU - Longyan Jiang AU - Suwan Sun AU - Tengyun Wang AU - Wangheng Hou AU - Tianying Zhang AU - Hua Zhu AU - Jun Zhang AU - Quan Yuan AU - Tong Cheng AU - Jun Li AU - Ningshao Xia Y1 - 2019/11/01 UR - http://gut.bmj.com/content/68/11/2044.abstract N2 - Objective Developing a small animal model that accurately delineates the natural history of hepatitis B virus (HBV) infection and immunopathophysiology is necessary to clarify the mechanisms of host-virus interactions and to identify intervention strategies for HBV-related liver diseases. This study aimed to develop an HBV-induced chronic hepatitis and cirrhosis mouse model through transplantation of human bone marrow mesenchymal stem cells (hBMSCs).Design Transplantation of hBMSCs into Fah-/-Rag2-/-IL-2Rγc-/- SCID (FRGS) mice with fulminant hepatic failure (FHF) induced by hamster-anti-mouse CD95 antibody JO2 generated a liver and immune cell dual-humanised (hBMSC-FRGS) mouse. The generated hBMSC-FRGS mice were subjected to assessments of sustained viremia, specific immune and inflammatory responses and liver pathophysiological injury to characterise the progression of chronic hepatitis and cirrhosis after HBV infection.Results The implantation of hBMSCs rescued FHF mice, as demonstrated by robust proliferation and transdifferentiation of functional human hepatocytes and multiple immune cell lineages, including B cells, T cells, natural killer cells, dendritic cells and macrophages. After HBV infection, the hBMSC-FRGS mice developed sustained viremia and specific immune and inflammatory responses and showed progression to chronic hepatitis and liver cirrhosis at a frequency of 55% after 54 weeks.Conclusion This new humanised mouse model recapitulates the liver cirrhosis induced by human HBV infection, thus providing research opportunities for understanding viral immune pathophysiology and testing antiviral therapies in vivo. ER -