Restoration of liver function in FAH-deficient mice repopulated with iPS cell–derived hepatocytes.
(A) In the absence of NTBC, a mouse with no digital chimerism is lethargic and shows signs of dehydration and lack of grooming (front), while a littermate with high levels of digital chimerism appears normal (back) at P22. (B–E) Blood analysis of liver function parameters at P22 in mice deprived of NTBC since P6. (B) Bilirubin and (C) albumin levels reflect the detoxification and protein synthesis functions of the liver, respectively. (D) Alkaline phosphatase (AP) is a marker of cholestasis, (E) while alanine aminotransferase (ALT) indicates hepatocyte injury. Mice with iPS cell contribution to the liver (all mice with high levels of digital chimerism, referred to as liver chimerism) have values indistinguishable from wild-type mice (including undetectable bilirubin), while the results from mice with no liver chimerism (all mice with no/low levels of digital chimerism) and FAH-deficient mice indicate liver failure. Liver function parameters of the mice with liver chimerism were stable at reanalysis at P70 and P300 (Supplemental Figure 2). Data represent mean ± SEM. **P < 0.005; #P > 0.05.