Evaluation of a novel bioartificial liver in rats with complete liver ischemia:: treatment efficacy and species-specific α-GST detection to monitor hepatocyte viability
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作者:
Flendrig, LM
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机构:Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med G2 130, NL-1100 DE Amsterdam, Netherlands
Flendrig, LM
Chamuleau, RAFM
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机构:Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med G2 130, NL-1100 DE Amsterdam, Netherlands
Chamuleau, RAFM
Maas, MAW
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机构:Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med G2 130, NL-1100 DE Amsterdam, Netherlands
Maas, MAW
Daalhuisen, J
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机构:Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med G2 130, NL-1100 DE Amsterdam, Netherlands
Daalhuisen, J
Hasset, B
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机构:Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med G2 130, NL-1100 DE Amsterdam, Netherlands
Hasset, B
Kilty, CG
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机构:Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med G2 130, NL-1100 DE Amsterdam, Netherlands
Kilty, CG
Doyle, S
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机构:Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med G2 130, NL-1100 DE Amsterdam, Netherlands
Doyle, S
Ladiges, NCJJ
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机构:Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med G2 130, NL-1100 DE Amsterdam, Netherlands
Ladiges, NCJJ
Jörning, GGA
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机构:Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med G2 130, NL-1100 DE Amsterdam, Netherlands
Jörning, GGA
la Soe, JW
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机构:Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med G2 130, NL-1100 DE Amsterdam, Netherlands
la Soe, JW
Sommeijer, D
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机构:Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med G2 130, NL-1100 DE Amsterdam, Netherlands
Sommeijer, D
te Velde, AA
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机构:Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med G2 130, NL-1100 DE Amsterdam, Netherlands
te Velde, AA
机构:
[1] Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med G2 130, NL-1100 DE Amsterdam, Netherlands
Background/Aims: There is an urgent need for an effective bioartificial liver system to bridge patients with fulminant hepatic failure to liver transplantation or to regeneration of their own liver. Recently, we proposed a bioreactor with a novel design for use as a bioartificial liver (BAL). The reactor comprises a spirally wound nonwoven polyester fabric in which hepatocytes are cultured (40 . 10(6) cells/ml) as small aggregates and homogeneously distributed oxygenation tubing for decentralized oxygen supply and CO2 removal. The aims of this study were to evaluate the treatment efficacy of our original porcine hepatocyte-based BAL in rats with fulminant hepatic failure due to liver ischemia (LIS) and to monitor the viability of the porcine hepatocytes in the bioreactor during treatment. The latter aim is novel and was accomplished by applying a new species-specific enzyme immunoassay (EIA) for the determination of porcine alpha-glutathione S-transferase (alpha-GST), a marker for hepatocellular damage. Methods: Three experimental groups were studied: the first control group (LIS Control, n=13) received a glucose infusion only; a second control group (LLS No-Cell-BAL, n=8) received BAL treatment without cells; and the treated group (LIS Cell-BAL, n=8) was connected to our BAL which had been seeded with 4.4 . 10(8) viable primary porcine hepatocytes. Results/Conclusions: In contrast to previous comparable studies, BAL treatment significantly improved survival time in recipients with LIS. In addition, the onset of hepatic encephalopathy was significantly delayed and the mean arterial blood pressure significantly improved. Significantly lower levels of ammonia and lactate in the LIS Cell-BAL group indicated that the porcine hepatocytes in the bioreactor were metabolically activity. Low pig alpha-GST levels suggested that our bioreactor was capable of maintaining hepatocyte viability during treatment. These results provide a rationale for a comparable study in LIS-pigs as a next step towards potential clinical application.
机构:
UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USAUNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USA
Baquerizo, A
Mhoyan, A
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UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USAUNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USA
Mhoyan, A
Shirwan, H
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机构:
UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USAUNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USA
Shirwan, H
Swensson, J
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UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USAUNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USA
Swensson, J
Busuttil, RW
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UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USAUNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USA
Busuttil, RW
Demetriou, AA
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UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USAUNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USA
Demetriou, AA
Cramer, DV
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UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USAUNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USA
机构:
UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USAUNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USA
Baquerizo, A
Mhoyan, A
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h-index: 0
机构:
UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USAUNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USA
Mhoyan, A
Shirwan, H
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机构:
UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USAUNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USA
Shirwan, H
Swensson, J
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机构:
UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USAUNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USA
Swensson, J
Busuttil, RW
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机构:
UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USAUNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USA
Busuttil, RW
Demetriou, AA
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机构:
UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USAUNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USA
Demetriou, AA
Cramer, DV
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机构:
UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USAUNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, DEPT SURG, LIVER TRANSPLANT PROGRAM, LOS ANGELES, CA 90048 USA