Advances in cell sources of hepatocytes for bioartificial liver

Xiao-Ping Pan and Lan-Juan Li
Hangzhou, China

BACKGROUND: Orthotopic liver transplantation (OLT) is the
most effective therapy for liver failure. However, OLT is severely
limited by the shortage of liver donors. Bioartificial liver (BAL)
shows great potential as an alternative therapy for liver failure.
In recent years, progress has been made in BAL regarding
genetically engineered cell lines, immortalized human
hepatocytes, methods for preserving the phenotype of primary
human hepatocytes, and other functional hepatocytes derived
from stem cells.
DATA SOURCES: A systematic search of PubMed and ISI Web
of Science was performed to identify relevant studies in English
language literature using the key words such as liver failure,
bioartificial liver, hepatocyte, stem cells, differentiation, and
immortalization. More than 200 articles related to the cell
sources of hepatocyte in BAL were systematically reviewed.
RESULTS: Methods for preserving the phenotype of primary
human hepatocytes have been successfully developed. Many
genetically engineered cell lines and immortalized human
hepatocytes have also been established. Among these cell lines,
the incorporation of BAL with GS-HepG2 cells or alginateencapsulated
HepG2 cells could prolong the survival time and
improve pathophysiological parameters in an animal model
of liver failure. The cBAL111 cells were evaluated using the
AMC-BAL bioreactor, which could eliminate ammonia and
lidocaine, and produce albumin. Importantly, BAL loading
with HepLi-4 cells could significantly improve the blood
biochemical parameters, and prolong the survival time in pigs
with liver failure. Other functional hepatocytes differentiated
from stem cells, such as human liver progenitor cells, have been
successfully achieved.
CONCLUSIONS: Aside from genetically modified liver cell
lines and immortalized human hepatocytes, other functional hepatocytes derived from stem cells show great potential as cell
sources for BAL. BAL with safe and effective liver cells may be
achieved for clinical liver failure in the near future.
(Hepatobiliary Pancreat Dis Int 2012;11:594-605)