Influence of Serum from Rats with Fulminant Hepatic Failure on Hepatocytes in a Bioartificial Liver System

  title={Influence of Serum from Rats with Fulminant Hepatic Failure on Hepatocytes in a Bioartificial Liver System},
  author={Y Ito and Susumu Eguchi and Yukio Kamohara and Hiroyuki Inuo and Kosho Yamanouchi and Sadayuki Okudaira and Katsuhiko Yanaga and Junichiro Furui and Takashi Kanematsu},
  journal={The International Journal of Artificial Organs},
  pages={303 - 310}
Fulminant hepatic failure (FHF) is a life-threatening condition marked by many excessively increased unmetabolized toxins and growth factors. Recently developed bioartificial liver (BAL) systems containing hepatocytes can be used to treat patients with FHF. However, the behavior of these hepatocytes on exposure to FHF serum in vitro remains unclear. In the present study, we used FHF rat models and the sera from these rats (i.e., FHF serum) contained elevated inflammatory cytokines (TNF-α, IL-1… 
The effect of rat acute-liver-failure plasma on HepaRG cells.
HepaRG cells are negatively affected by rat plasma, even of healthy origin, but their ammonia eliminating capacity is relatively resistant, underlining their suitability for BAL application.
Protective effects of ACLF sera on metabolic functions and proliferation of hepatocytes co-cultured with bone marrow MSCs in vitro.
ACLF serum does not impair the cell morphology, viability, proliferation and overall metabolic capacities of hepatocyte co-cultured with MSCs in vitro.
Alginate-encapsulated HepG2 cells in a fluidized bed bioreactor maintain function in human liver failure plasma.
Data show that in LF plasma, alginate-encapsulated HepG2 cells can maintain viability, and metabolic, synthetic, and detoxificatory activities, indicating that the system can be scaled-up to form the biological component of a bioartificial liver.
Optimized performance of the integrated hepatic cell-loaded cryogel-based bioreactor with intermittent perfusion of acute liver failure plasma.
A hybrid bioreactor that integrates a hepatic cell-loaded cryogel disc and an activated carbon cloth in one compact unit is designed with potential application as a bioartificial liver support and its functionality and longevity in the presence of intermittent exposure to ALF plasma is analyzed.
Effects of acute‐liver‐failure‐plasma exposure on hepatic functionality of HepaRG‐AMC‐Bioartificial Liver
  • G. Nibourg, R. Hoekstra, +4 authors R. Chamuleau
  • Biology, Medicine
    Liver international : official journal of the International Association for the Study of the Liver
  • 2013
The AMC‐bioartificial liver loaded with the human hepatoma cell line HepaRG as biocomponent (HepaRG‐AMC‐BAL) has recently proven efficacious in rats with acute liver failure (ALF). However, its
Fabrication of macroporous cryogels as potential hepatocyte carriers for bioartificial liver support.
Cryogel-based closed continuous bioreactor systems could maintain HepG2 cells at high density for 7 days and showed the ability of immobilized cells to detoxify circulating plasma obtained from patients with acute on chronic liver failure (ACLF).
Evaluation of liver support systems for preclinical testing by animal trials.
Various animal models of acute liver failure are reviewed with respect to their suitability for evaluating liver support systems (LSS) according to envisaged modes of therapy to increase the value of the preclinical testing of LSS.
Human liver cell lines for the AMC-bioartificial liver
De HepaRG-levercellijn is een veelbelovend biologisch component voor het maken van de kunstlever AMC-BAL. Geert Nibourg werkte aan een humane levercellijn die beschikbaar is in ruime hoeveelheden en


Treatment of Acute Liver Failure in Pigs Reduces Hepatocyte Function in a Bioartificial Liver Support System
The results show that hepatocytes in the BAL remained viable after 24 h treatment of anhepatic pigs, as shown by the LDH release and pseudocholine esterase production, however, metabolic functions such as ammonia clearance, ECOD and urea synthesis were reduced after 24h exposure of hepatocytes to autologous ALF plasma, whereas these functions were unaltered after 24H culturing of the cells in the bioreactor.
Fulminant hepatic failure in rats: Survival and effect on blood chemistry and liver regeneration
A novel model of FHF in rats is developed that has a number of physiological and biochemical features seen clinically in FHF, including severely impaired ability of the residual liver tissue to regenerate, and changes in blood chemistry reflected rapid development of liver failure.
Rapid inhibition of DNA synthesis in hepatocytes from regenerating rat liver by serum from patients with fulminant hepatic failure.
Investigation of the acute effects of serum from patients with fulminant hepatic failure on isolated hepatocytes from normal and regenerating rat livers found a specific inhibitory effect of FHF serum on DNA synthesis in hepatocyte from regenerating livers.
Clinical significance of human hepatocyte growth factor in blood from patients with fulminant hepatic failure
The results suggest that human hepatocyte growth factor in blood from patients with fulminant hepatic failure is a physiological hepato‐trophic factor and plays an important role in liver regeneration of patients.
Inhibition of signal transducer and activator transcription factor 3 in rats with acute hepatic failure.
It is shown that in rats with critically low hepatocyte mass, whether with or without ongoing liver cell necrosis, inhibition of liver regeneration is associated with early and sustained increase in blood IL-6 levels, and that after massive hepatocyte loss, an early and rapid rise inBlood IL- 6 levels may weaken the hepatic regenerative response through up-regulation of Stat3 inhibitors PIAS3 and SOCS-1.
Clinical use of a bioartificial liver in the treatment of acetaminophen-induced fulminant hepatic failure.
The BAL support system seems to improve the outcome of high-risk patients with acetaminophen-induced fulminant hepatic failure, even in the absence of liver transplantation.
Increase in albumin mRNA by repeated intrahepatic transplantation of F344 rat hepatocytes into the liver of congenic analbuminemic rats.
The results demonstrate that the number of intrahepatically transplanted hepatocytes is able to be increased by repeated infusion, and the transplantability was confirmed by the increase in theNumber of albumin-positive cells and appearance of normal albumin mRNA within the recipient liver, andThe elevated serum albumin level.
Levels of the human hepatocyte growth factor in serum of patients with various liver diseases determined by an enzyme‐linked immunosorbent assay
Serum human hepatocyte growth factor levels in patients with acute hepatitis, chronic hepatitis and cirrhosis were found to be slightly higher than those in normal subjects, but only the increase in serum human hepatocytes growth factor of acute hepatitis patients was statistically significant.
Changes in liver regenerative factors in a case of living‐related liver transplantation
The liver of the patient with FHF did not respond to liver regenerative stimulus, in part, through involvement of inhibitor TGF‐β, and the HGF/c‐met system is thought to be involved in the mechanism of regeneration.
In patients with FHF, TNF production was increased and correlated closely with activity of interleukin-1, another cytokine that is released by monocytes/macrophages in response to infection and endotoxin and is produced in increased quantities in FHF.