PMID- 22719943
OWN - NLM
STAT- MEDLINE
DCOM- 20121213
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 6
DP  - 2012
TI  - Liver progenitor cell line HepaRG differentiated in a bioartificial liver 
      effectively supplies liver support to rats with acute liver failure.
PG  - e38778
LID - 10.1371/journal.pone.0038778 [doi]
LID - e38778
AB  - A major roadblock to the application of bioartificial livers is the need for a 
      human liver cell line that displays a high and broad level of hepatic 
      functionality. The human bipotent liver progenitor cell line HepaRG is a 
      promising candidate in this respect, for its potential to differentiate into 
      hepatocytes and bile duct cells. Metabolism and synthesis of HepaRG monolayer 
      cultures is relatively high and their drug metabolism can be enhanced upon 
      treatment with 2% dimethyl sulfoxide (DMSO). However, their potential for 
      bioartificial liver application has not been assessed so far. Therefore, HepaRG 
      cells were cultured in the Academic Medical Center bioartificial liver (AMC-BAL) 
      with and without DMSO and assessed for their hepatic functionality in vitro and 
      in a rat model of acute liver failure. HepaRG-AMC-BALs cultured without DMSO 
      eliminated ammonia and lactate, and produced apolipoprotein A-1 at rates 
      comparable to freshly isolated hepatocytes. Cytochrome P450 3A4 transcript levels 
      and activity were high with 88% and 37%, respectively, of the level of 
      hepatocytes. DMSO treatment of HepaRG-AMC-BALs reduced the cell population and 
      the abovementioned functions drastically. Therefore, solely HepaRG-AMC-BALs 
      cultured without DMSO were tested for efficacy in rats with acute liver failure 
      (n = 6). HepaRG-AMC-BAL treatment increased survival time of acute liver failure 
      rats  approximately 50% compared to acellular-BAL treatment. Moreover, HepaRG-AMC-BAL treatment 
      decreased the progression of hepatic encephalopathy, kidney failure, and ammonia 
      accumulation. These results demonstrate that the HepaRG-AMC-BAL is a promising 
      bioartificial liver for clinical application.
FAU - Nibourg, Geert A A
AU  - Nibourg GA
AD  - Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, 
      University of Amsterdam, Amsterdam, The Netherlands.
FAU - Chamuleau, Robert A F M
AU  - Chamuleau RA
FAU - van der Hoeven, Tessa V
AU  - van der Hoeven TV
FAU - Maas, Martinus A W
AU  - Maas MA
FAU - Ruiter, An F C
AU  - Ruiter AF
FAU - Lamers, Wouter H
AU  - Lamers WH
FAU - Oude Elferink, Ronald P J
AU  - Oude Elferink RP
FAU - van Gulik, Thomas M
AU  - van Gulik TM
FAU - Hoekstra, Ruurdtje
AU  - Hoekstra R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120618
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Animals
MH  - *Cell Differentiation
MH  - Liver/*pathology
MH  - Liver Failure, Acute/pathology/*therapy
MH  - *Liver, Artificial
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stem Cells/*pathology
PMC - PMC3377721
COIS- Competing Interests: RC is CSO of Hep-Art Medical Devices, which has the 
      exclusive license of the AMC bioartificial liver. However, he owns no shares of 
      the company. Hep-Art was established in 2000 to commercialize the AMC-BAL. 
      Hep-Art worked on developing a suitable human cell line until it ran out of 
      funding early 2007. Since then it halts its operations. Address: Hep-Art Medical 
      Devices BV. Reimersbeek 27, 1085 AE Amsterdam, The Netherlands. 
      http://www.hep-art.com. Hep-Art Medical Devices BV also provided part of the 
      funding for this study. GN, RC and RH have submitted a patent describing the 
      culture method. RH was employed by Hep-Art Medical Devices for 6 months. The 
      other authors who have taken part in this study declare that they do not have 
      anything to disclose regarding funding or conflict of interest with respect to 
      this manuscript. There are no products in development or marketed products to 
      declare. This does not alter the authors' adherence to all the PLoS ONE policies 
      on sharing data and materials.
EDAT- 2012/06/22 06:00
MHDA- 2012/12/14 06:00
PMCR- 2012/06/18
CRDT- 2012/06/22 06:00
PHST- 2012/01/30 00:00 [received]
PHST- 2012/05/10 00:00 [accepted]
PHST- 2012/06/22 06:00 [entrez]
PHST- 2012/06/22 06:00 [pubmed]
PHST- 2012/12/14 06:00 [medline]
PHST- 2012/06/18 00:00 [pmc-release]
AID - PONE-D-12-03021 [pii]
AID - 10.1371/journal.pone.0038778 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(6):e38778. doi: 10.1371/journal.pone.0038778. Epub 2012 Jun 18.