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

L. M. Flendrig; R. A. Chamuleau; M. A. Maas; J. Daalhuisen; B. Hasset; C. G. Kilty; S. Doyle; N. C. Ladiges; G. G. Jörning; J. W. la Soe; D. Sommeijer; A. A. te Velde

doi:https://doi.org/10.1016/S0168-8278(99)80078-6

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

L. M. Flendrig, R. A. Chamuleau, M. A. Maas, J. Daalhuisen, B. Hasset, C. G. Kilty, S. Doyle, N. C. Ladiges, G. G. Jörning, J. W. la Soe, D. Sommeijer, A. A. te Velde

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Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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 x 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 (LIS 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 x 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

Original language	English
Pages (from-to)	311-320
Journal	Journal of Hepatology
Volume	30
Issue number	2
DOIs	https://doi.org/10.1016/S0168-8278(99)80078-6
Publication status	Published - 1999

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Flendrig, L. M., Chamuleau, R. A., Maas, M. A., Daalhuisen, J., Hasset, B., Kilty, C. G., Doyle, S., Ladiges, N. C., Jörning, G. G., la Soe, J. W., Sommeijer, D., & te Velde, A. A. (1999). Evaluation of a novel bioartificial liver in rats with complete liver ischemia: treatment efficacy and species-specific alpha-GST detection to monitor hepatocyte viability. Journal of Hepatology, 30(2), 311-320. https://doi.org/10.1016/S0168-8278(99)80078-6

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

abstract = "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 x 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 (LIS 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 x 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",

author = "Flendrig, {L. M.} and Chamuleau, {R. A.} and Maas, {M. A.} and J. Daalhuisen and B. Hasset and Kilty, {C. G.} and S. Doyle and Ladiges, {N. C.} and J{\"o}rning, {G. G.} and {la Soe}, {J. W.} and D. Sommeijer and {te Velde}, {A. A.}",

year = "1999",

doi = "https://doi.org/10.1016/S0168-8278(99)80078-6",

language = "English",

volume = "30",

pages = "311--320",

journal = "Journal of Hepatology",

issn = "0168-8278",

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Flendrig, LM, Chamuleau, RA, Maas, MA, Daalhuisen, J, Hasset, B, Kilty, CG, Doyle, S, Ladiges, NC, Jörning, GG, la Soe, JW, Sommeijer, D & te Velde, AA 1999, 'Evaluation of a novel bioartificial liver in rats with complete liver ischemia: treatment efficacy and species-specific alpha-GST detection to monitor hepatocyte viability', Journal of Hepatology, vol. 30, no. 2, pp. 311-320. https://doi.org/10.1016/S0168-8278(99)80078-6

Evaluation of a novel bioartificial liver in rats with complete liver ischemia: treatment efficacy and species-specific alpha-GST detection to monitor hepatocyte viability. / Flendrig, L. M.; Chamuleau, R. A.; Maas, M. A. et al.
In: Journal of Hepatology, Vol. 30, No. 2, 1999, p. 311-320.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Evaluation of a novel bioartificial liver in rats with complete liver ischemia: treatment efficacy and species-specific alpha-GST detection to monitor hepatocyte viability

AU - Flendrig, L. M.

AU - Chamuleau, R. A.

AU - Maas, M. A.

AU - Daalhuisen, J.

AU - Hasset, B.

AU - Kilty, C. G.

AU - Doyle, S.

AU - Ladiges, N. C.

AU - Jörning, G. G.

AU - la Soe, J. W.

AU - Sommeijer, D.

AU - te Velde, A. A.

PY - 1999

Y1 - 1999

N2 - 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 x 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 (LIS 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 x 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

AB - 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 x 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 (LIS 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 x 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

U2 - https://doi.org/10.1016/S0168-8278(99)80078-6

DO - https://doi.org/10.1016/S0168-8278(99)80078-6

M3 - Article

C2 - 10068112

SN - 0168-8278

VL - 30

SP - 311

EP - 320

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 2

ER -