Figure 1.

Generation of human bone marrow mesenchymal stem cells-Fah^-/- Rag2^-/- IL-2Rγc^-/-SCID (hBMSC-FRGS) mice through the transplantation of hBMSCs into fulminant hepatic failure (FHF)-FRGS mice. (A) Schematic design of the rescue of FRGS mice with life-threatening FHF by hBMSC transplantation, the generation of hBMSC-derived human hepatocytes and immune cell lineages, and the modelling of the progression of HBV infection-induced viremia, immune and inflammatory responses, antibody synthesis, chronic hepatitis and liver cirrhosis. (B) Schematic design of the cell transplantation treatments administered to mice. During the perioperative period, FHF-FRGS mice with or without hBMSC transplantation received the same treatments, including 2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) on-off treatment, JO2 and busulfan injection. FHF-FRGS mice with hBMSC transplantation received a splenic injection of 1×10⁶ hBMSCs at day 0. The normal FRGS mice were administered 100% NTBC in their drinking water without any extra treatment. (C) Survival analysis of mice in the three groups during the perioperative period. The survival of hBMSC-FRGS and normal FRGS mice was observed for 60 weeks (n=30/group). (D) Temporal changes in eight typical biochemical markers of liver function (n=8/group). (E) H&E staining of liver tissue collected from FHF-FRGS with or without hBMSC transplantation and normal FRGS mice (bar=50 µm). The yellow arrow indicates the haemorrhage point, the red arrow indicates dead cells and the black arrow indicates residual cells. a) P<0.05; b) p<0.01; c) p<0.001. ALT, alanine transaminase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; cccDNA, covalently closed circular DNA; DC, dendritic cell; HBcAg, hepatitis B core antigen; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; NS, not significant; PT, prothrombin time; TB, total bilirubin; TBA, total bile acid; TC, total cholesterol; TP, total protein.