HBV infection-induced liver cirrhosis development in dual-humanised mice with human bone mesenchymal stem cell transplantation
Lunzhi Yuan,Jing Jiang,Xuan Liu,Yali Zhang,Liang Zhang,Jiaojiao Xin,Kun Wu,Xiaoling Li,Jiali Cao,Guo Xueran,Dongyan Shi,Jun Li,Longyan Jiang,Suwan Sun,Tengyun Wang,Wangheng Hou,Tianying Zhang,Hua Zhu,Jun Zhang,Quan Yuan,Tong Cheng,Ningshao Xia +21 more
TLDR
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.Abstract:
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.read more
Citations
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Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer.
Yongyan Chen,Zhigang Tian +1 more
TL;DR: The current knowledge regarding hepatic innate lymphocytes with unique characteristics, including NK cells, ILC1/2/3s, NKT cells, γδ T cells, and MAIT cells are addressed and their potential roles in liver homeostasis maintenance and the progression of liver diseases and cancer are addressed.
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PBMC transcriptomics identifies immune-metabolism disorder during the development of HBV-ACLF.
Jiang Li,Xi Liang,Jing Jiang,Lingling Yang,Jiaojiao Xin,Dongyan Shi,Yingyan Lu,Jun Li,Keke Ren,Hozeifa Mohamed Hassan,Jianing Zhang,Pengcheng Chen,Heng Yao,Li Jiaqi,Tianzhou Wu,Linfeng Jin,Ping Ye,Tan Li,Huafen Zhang,Suwan Sun,Beibei Guo,Xingping Zhou,Qun Cai,Jiaxian Chen,Xiaowei Xu,Jianrong Huang,Shaorui Hao,Jinqiu He,Shaojie Xin,Di Wang,Jonel Trebicka,Xin Chen +31 more
TL;DR: The functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages and that immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF.
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Chronic hepatitis B and non-alcoholic fatty liver disease: Conspirators or competitors?
TL;DR: Recent advances in clinical and basic researches related to the underlying mutual interactions of non‐alcoholic fatty liver disease and chronic hepatitis B are summarized as well as potential animal models to facilitate further investigation.
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Animal Models of Hepatitis B Virus Infection-Success, Challenges, and Future Directions.
TL;DR: A review of the currently available animal models for research of HBV and HBV-related hepadnaviruses can be found in this article, where the authors discuss challenges and future directions for improvement.
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In vitro inhibition effects of hepatitis B virus by dandelion and taraxasterol
TL;DR: Dandelion and its component taraxasterol could inhibit HBV and may be a potential anti-HBV drug, whose potential targets were the host factors PTBP1 and SIRT1.
References
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Hepatitis B virus infection [1] (multiple letters)
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TL;DR: This Review discusses the development of these new generations of humanized mice, how they will facilitate translational research in several biomedical disciplines and approaches to overcome the remaining limitations of these models.
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Kuan Der Lee,Kuan Der Lee,Tom K. Kuo,Jacqueline Whang-Peng,Yu Fen Chung,Ching Tai Lin,Shiu Huey Chou,Jim Ray Chen,Yi Peng Chen,Oscar K. Lee +9 more
TL;DR: Human MSCs from different sources are able to differentiate into functional hepatocyte‐like cells and, hence, may serve as a cell source for tissue engineering and cell therapy of hepatic tissues and indicates that a revision of the definition may be required.
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