HBV infection-induced liver cirrhosis development in dual-humanised mice with human bone mesenchymal stem cell transplantation.
Gut
; 68(11): 2044-2056, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-30700543
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Hepatite B Crônica
/
Transplante de Células-Tronco Mesenquimais
/
Modelos Animais de Doenças
/
Cirrose Hepática
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article