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

被引:50
作者
Flendrig, LM
Chamuleau, RAFM
Maas, MAW
Daalhuisen, J
Hasset, B
Kilty, CG
Doyle, S
Ladiges, NCJJ
Jörning, GGA
la Soe, JW
Sommeijer, D
te Velde, AA
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med G2 130, NL-1100 DE Amsterdam, Netherlands
[2] Biotrin Int Co, Dublin, Ireland
关键词
alpha-GST; bioartificial liver; bioreactor; hepatocytes; liver support; oxygenator; polyester nonwoven; xenogeneic;
D O I
10.1016/S0168-8278(99)80078-6
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:311 / 320
页数:10
相关论文
共 49 条
  • [1] A NOVEL BIOREACTOR DESIGN FOR IN-VITRO RECONSTRUCTION OF IN-VIVO LIVER CHARACTERISTICS
    BADER, A
    KNOP, E
    BOKER, K
    FRUHAUF, N
    SCHUTTLER, W
    OLDHAFER, K
    BURKHARD, R
    PICHLMAYR, R
    SEWING, KF
    [J]. ARTIFICIAL ORGANS, 1995, 19 (04) : 368 - 374
  • [2] Xenoantibody response of patients with severe acute liver failure exposed to porcine antigens following treatment with a bioartificial liver
    Baquerizo, A
    Mhoyan, A
    Shirwan, H
    Swensson, J
    Busuttil, RW
    Demetriou, AA
    Cramer, DV
    [J]. TRANSPLANTATION PROCEEDINGS, 1997, 29 (1-2) : 964 - 965
  • [3] CORRELATION BETWEEN ELECTROENCEPHALOGRAPHIC AND BIOCHEMICAL INDEXES IN ACUTE HEPATIC-ENCEPHALOPATHY IN RATS
    CHAMULEAU, RAFM
    DEUTZ, NEP
    DEHAAN, JG
    VANGOOL, J
    [J]. JOURNAL OF HEPATOLOGY, 1987, 4 (03) : 299 - 306
  • [4] Galactosamine-induced fulminant hepatic necrosis in unanesthetized canines
    DiazBuxo, JA
    Blumenthal, S
    Hayes, D
    Gores, P
    Gordon, B
    [J]. HEPATOLOGY, 1997, 25 (04) : 950 - 957
  • [5] DEVELOPMENT OF A BIOARTIFICIAL LIVER USING ISOLATED HEPATOCYTES
    DIXIT, V
    [J]. ARTIFICIAL ORGANS, 1994, 18 (05) : 371 - 384
  • [6] DIXON FJ, 1958, ARCH PATHOL, V65, P18
  • [7] Circulatory, respiratory, cerebral, and renal derangements in acute liver failure: Pathophysiology and management
    Ellis, A
    Wendon, J
    [J]. SEMINARS IN LIVER DISEASE, 1996, 16 (04) : 379 - 388
  • [8] Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure
    Ellis, AJ
    Hughes, RD
    Wendon, JA
    Dunne, J
    Langley, PG
    Kelly, JH
    Gislason, GT
    Sussman, NL
    Williams, R
    [J]. HEPATOLOGY, 1996, 24 (06) : 1446 - 1451
  • [9] FARGHALI H, 1994, PHYSIOL RES, V43, P121
  • [10] Flendrig LM, 1997, ARTIF ORGANS, V21, P1177