Evaluation of a reversibly immortalized human hepatocyte line in bioartificial liver in pigs
Keywords:
Reversible immortalization, hepatocytes, bioartificial liver, fulminant hepatic failure.Abstract
An appropriate cell source is essential for the clinical application of bioartificial liver (BAL) system. This study
aimed to test a reversibly immortalized human hepatocyte line (HepLi-4) in our newly validated choanoid fluidized
bed bioreactor based BAL in pigs with fulminant hepatic failure (FHF). 15 FHF pigs were allocated to three
groups: a BAL group receiving BAL treatment with HepLi-4 cells; a sham BAL group receiving cell-free BAL
treatment; and a FHF group receiving intensive care only. Expression of liver-specific genes in HepLi-4 cells
before and after BAL was analyzed, adult human hepatocytes acted as a reference. In BAL group, Fischer index
was higher and serum indirect bilirubin level was lower compared with two control groups. Survival time in BAL
group was longer than that in two control groups, but the difference was not statistically significant. Gene
expression analysis showed that the transcript levels of liver-specific genes in HepLi-4 were retained after BAL,
but significant variations were observed between HepLi-4 and human hepatocytes. HepLi-4 showed beneficial
metabolic effects on FHF pigs in BAL, but is still not an appropriate cell source for BAL. More insights into
interpreting the conditions for hepatocyte differentiation are needed.v
