Evaluation of a novel bioartificial liver in rats with complete liver ischemia: treatment efficacy and species-specific α-GST detection to monitor hepatocyte viability

Flendrig, Leonard M.; Chamuleau, R. A. F. M.; Maas, Marjolein; Daalhuisen, Joost; Hasset, Brian; Kilty, Cormac G.; Doyle, Seán; Ladiges, N.C.J.J.; Jörning, G.G.A.; Soe, J.W. La; Sommeijer, Dirkje W.; Velde, Anje A. te

doi:10.1016/s0168-8278(99)80078-6

Cited by 58 publications

(29 citation statements)

References 37 publications

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“…In many different models of ALF several BALs based on animal liver cells have shown to prolong survival significantly in comparison to standard treatment [23][24][25][26][27][28][29][30][31][32][33] .…”

Section: How Good Are Results In Experimental Animals?mentioning

confidence: 99%

Future of bioartificial liver support

Chamuleau¹

2009

WJGS

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Many different artificial liver support systems (biological and non-biological) have been developed, tested preclinically and some have been applied in clinical trials. Based on theoretical considerations a biological artificial liver (BAL) should be preferred above the non-biological ones. However, clinical application of the BAL is still experimental. Here we try to analyze which hurdles have to be taken before the BAL will become standard equipment in the intensive care unit for patients with acute liver failure or acute deterioration of chronic liver disease.

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Section: How Good Are Results In Experimental Animals?mentioning

confidence: 99%

Future of bioartificial liver support

Chamuleau¹

2009

WJGS

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“…The stirred bioreactor setup is adequate for cell mass production. However, for liver substitution in bioartificial applications bioreactors with a dense oxygenation supply like hollow fiber systems (Flendrig et al, 1999;Gerlach et al, 1994) are recommended.…”

Section: Discussionmentioning

confidence: 99%

Cultivation of immortalized human hepatocytes HepZ on macroporous CultiSpher G microcarriers

Werner

Duvar

Müthing

et al. 2000

Biotechnol. Bioeng.

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“…downscaled bioreactor of the second-generation AMC-BAL [van de Kerkhove et al, 2005] with an internal volume of 10 ml and double number of gas capillaries [Poyck et al, 2007c]. The general configuration of the bioreactor, as described in detail by Flendrig et al [1997Flendrig et al [ , 1999, consists of a polycarbonate housing containing a 3D non-woven hydrophilic polyester matrix circularly wound around a polycarbonate core. Between the matrix layers, hydrophobic polypropylene gas capillaries are situated in a parallel fashion of which the ends are embedded in polyurethane resin and fitted with gas inlet and outlet caps.…”

Section: Bioreactormentioning

confidence: 99%

“…These extracorporeal devices contain large amounts of hepatocytes to support the wide array of liver functions of the failing liver, e.g., ammonia detoxification. In the Academic Medical Center (AMC) in Amsterdam, we developed the AMC-BAL that is characterized by direct contact between cells and plasma, an integrated oxygenation system through gas capillaries and a spirally wound polyester matrix [Flendrig et al, 1997[Flendrig et al, , 1999. Liver cells cultured in the AMC-BAL display 2-fold higher and more stable functionality compared with cells cultured in monolayer [Flendrig et al, 1997].…”

Section: Introductionmentioning

confidence: 99%

Expression of Glutamine Synthetase and Carbamoylphosphate Synthetase I in a Bioartificial Liver: Markers for the Development of Zonation in vitro

Poyck

Hoekstra²,

Vermeulen³

et al. 2008

Cells Tissues Organs

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Background: Mechanisms underlying hepatic zonation are not completely elucidated. In vitro test systems may provide new insights into current hypotheses. In this study, zonally expressed proteins, i.e. glutamine synthetase (GS; pericentral) and carbamoylphosphate synthetase (CPS; periportal), were tested for their expression patterns in the bioartificial liver of the Academic Medical Center (AMC-BAL). Methods: Distribution and organization of porcine hepatocytes inside the AMC-BAL as well as GS and CPS expression were analyzed (immuno-)histochemically in time. Ten zonally expressed proteins were analyzed by RT-PCR on cell isolate and bioreactor samples. General metabolic and hepatocyte-specific functions were determined as well. Results: Viable hepatocyte layers of approximately 150 µm were observed around gas capillaries, whereas inside the matrix, single cells or small aggregates were present. GS protein and mRNA levels were upregulated in time. GS protein was preferentially expressed in hepatocytes adjacent to oxygen-supplying capillaries and in previously CPS-positive hepatocytes. No shift towards a periportal or pericentral phenotype was observed from RT-PCR analysis. Conclusion: Induction of GS expression inside the AMC-BAL is not dependent of (low) oxygen tensions and hepatic nuclear factor 4α transcript levels. GS expression might be related to (1) low substrate levels and/or autocrine soluble factors, or (2) to cytoskeleton interactions, putatively associated with the β-catenin signaling pathway.

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Evaluation of a novel bioartificial liver in rats with complete liver ischemia: treatment efficacy and species-specific α-GST detection to monitor hepatocyte viability

Cited by 58 publications

References 37 publications

Future of bioartificial liver support

Future of bioartificial liver support

Cultivation of immortalized human hepatocytes HepZ on macroporous CultiSpher G microcarriers

Expression of Glutamine Synthetase and Carbamoylphosphate Synthetase I in a Bioartificial Liver: Markers for the Development of Zonation in vitro

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