Proliferative human cell sources applied as biocomponent in bioartificial livers: a review.
BACKGROUND
Bioartificial livers (BALs) are urgently needed to bridge severe liver failure patients to liver transplantation or liver regeneration. When based on primary hepatocytes, their efficacy has been shown in animal experiments and their safety was confirmed in clinical trials. However, a proliferative human cell source with therapeutic functionality is needed to secure availability and move BAL application forward.


METHODS
This review compares the performance of BALs based on proliferative human biocomponents and primary hepatocytes. This review evaluates relevant studies identified by searching the MEDLINE database until July 2011 and some of our own unpublished data.


CONCLUSIONS
All the discussed hepatocyte-like biocomponents show deficiencies in their hepatic functionality compared with primary hepatocytes, particularly functions occurring late in liver development. Nonetheless, the HepaRG, HepG2-GS-CYP3A4, and mesenchymal stem cells show efficacy in a statistically well-powered animal model of acute liver failure, when applied in a BAL device. Various methods to gain higher functionality of BALs, including genetic modification, the usage of combinatory cell sources, and improvement of culture methods, have scarcely been applied, but may further pave the path for BAL application. Clinical implementation of a BAL based on a human proliferative biocomponent is still several years away.
University of Amsterdam, Academic Medical Center, Department of Experimental Surgery (Surgical Laboratory; IWO 1A.1-117), Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Geert A A
GA
Nibourg
Robert A F M
RA
Chamuleau
Thomas M
TM
van Gulik
Ruurdtje
R
Hoekstra
D001672:Biocompatible Materials; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006801:Humans; D019164:Liver, Artificial; D013234:Stem Cells / Q000166:cytology
D001672:Biocompatible Materials