Improvement of serum amino acid profile in hepatic failure with the bioartificial liver using multicellular hepatocyte spheroids

Shiraha, Hidenori; Koide, Naoki; Hada, Hajime; Ujike, Kozo; Nakamura, Masaki; Shinji, Toshiyuki; Gotoh, Sachiko; Tsuji, Takao

doi:10.1002/(sici)1097-0290(19960520)50:4<416::aid-bit8>3.0.co;2-o

Cited by 29 publications

(12 citation statements)

References 14 publications

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“…Then, formed hepatocyte spheroids containing (1.0 − 3.1) × 10 10 hepatocytes were inoculated into the hollow fiber bioreactor. The hepatocyte density in the hollow fiber cartridge was about 3.0 × 10 7 cells/ml, which was almost comparable to that used by Sakai et al (34). The results showed that the hepatocytes maintained typical structure, and tight junctions between hepatocytes were observed.…”

Section: Discussionsupporting

confidence: 78%

“…Wu et al (33) also reported that hepatocyte spheroids maintained higher P450 activity than monolayers on collagen and demonstrated that the higher P450 activity within spheroids was associated with their ability to maintain a greater degree of differentiation compared to the monolayer. Shiraha et al (34) found that the ratio of BCAA/AAA in serum from a patient with hepatic failure increased by the BAL treatment using multicellular hepatocyte spheroids. Sakai et al (35) used a BAL with a spin filter‐type bioreactor based on suspension perfusion culture of porcine hepatocyte spheroids to perform the perfusion test of culture medium and 100% human plasma for 8 h. Their results indicated that the spheroid in the bioreactor had almost the same functions on a unit‐cell basis as those in small‐scale rotational culture.…”

Section: Discussionmentioning

confidence: 99%

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Bioartificial Liver Inoculated with Porcine Hepatocyte Spheroids for Treatment of Canine Acute Liver Failure Model

Chen

Ding

et al. 2003

Artificial Organs

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The aim of this study was to evaluate a novel bioartificial system in a canine model of acute liver failure. An acute liver failure model in canines was induced by an end-side portocaval shunt combined with common bile duct ligation and transection. The bioartificial liver system, which utilized blood perfusion through a hollow fiber bioreactor from BIOLIV A3A inoculated with 1.0 - 3.1 x 1010 porcine hepatocyte spheroids, was developed for the treatment of acute liver failure. Sixteen acute liver failure model canines were divided between a group treated with bioartificial liver (n=8) and a control group (n=8) for 5 h. Blood alanine aminotransferase (ALT), alkaline phosphatase (AKP), total bilirubin (TBi), direct bilirubin (DBi), prothrombin time (PT), ammonia levels, and the ratio of branched chain to aromatic amino acids (Fischer's ratio) were determined. ALT, AKP, TBi, DBi, and ammonia levels were significantly elevated, PT was significantly prolonged, and Fischer's ratio decreased significantly in the canine model of the two groups on day 14 after operation compared to baseline. There were no significant differences between the two groups in laboratory data before treatment. In canines treated with the bioartificial liver system, ALT, AKP, TBi, DBi, and ammonia levels decreased significantly, PT was significantly shortened, Fischer's ratio was significantly elevated after treatment, and the survival rate by day 7 after treatment was 100%. In canines in the control group, on the other hand, there were no significant differences in ALT, AKP, TBi, DBi, PT, and ammonia levels between pretreatment and posttreatment, though these indices decreased to a slight degree after treatment. The survival rate by day 7 after treatment was 62.5% in the control group. Fischer's ratio decreased after treatment. ALT, AKP, TBi, DBi, PT, and ammonia levels in the bioartificial liver system group were lower, and Fischer's ratio and survival rate were higher than those in the control group after treatment. These results indicate that the novel bioartificial liver system we developed has a significant impact on the course of canine acute liver failure model and has potential advantages for clinical use in patients with acute liver failure.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Bioartificial Liver Inoculated with Porcine Hepatocyte Spheroids for Treatment of Canine Acute Liver Failure Model

Chen

Ding

et al. 2003

Artificial Organs

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“…, porous gelatin sponges(Lin et al 1995), a multicompartment capillary system(Gerlach et al 1995), polyurethane foam(Matsushita et al 1991), or simply agarose (e.g Shiraha et al 1996). have been applied.…”

mentioning

confidence: 99%

“…Bader et al 1996) but also spheroids grown on diverse nonadherent surfaces, such as hepatocyte spheroids of human or animal origin (i.e. Nyberg et alTong et al 1994;Li et al 1992;Ueno et al 1992;Yagi et al 1993;Yuasa et al 1993;Nemoto et al 1995;Niwa et al 1996;Ota et al 1996;Peshwa et al 1996;Shiraha et al 1996;Wu et al 1996). In general, cocultivation of normal cells, with layers of feeder cells, e.g.…”

mentioning

confidence: 99%

Multicellular spheroids: a three‐dimensionalin vitroculture system to study tumour biology

Kunz-Schughart

Kreutz

Knuechel

1998

Int J Experimental Path

305

231

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The growth of tumour cells as three-dimensional multicellular spheroids in vitro has led to important insights in tumour biology, since properties of the in vivo-tumour such as proliferation or nutrient gradients, can be studied under controlled conditions. While this review starts with an update of recent data on spheroid monocultures, especially concerning tumour microenvironment and therapeutic modalities, the main emphasis is put on the spectrum of heterologous cultures which have evolved in previous years. This type of culture includes tumour cell interaction with endothelial, fibroblast or immunocompetent cells. The relation of the spheroid culture model to other types of three-dimensional culture and our critical evaluation and presentation of the technical aspects of growing and analysing spheroids are included in the text. These topics are chosen to help the experimental pathologist design experiments with tumour spheroids and to stimulate discussion.

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“…Media WE, 199, and HM produced comparable amounts aerobic metabolism (8,39) and the metabolism of the gluconeogenic amino acids alanine, threonine, valine, asparof urea at all days. There was significantly higher production of urea by medium 1640 compared to media 199 tate, and methionine (15,41). The two-way ANOVA for lactate, aspartate, and methionine was not statistically and WE on days 2 and 4 and compared to the other three media on day 6.…”

Section: Sample Preparation For Nmr Spectroscopy Samplesmentioning

confidence: 99%

Comparison of Bioenergetic Activity of Primary Porcine Hepatocytes Cultured in Four Different Media

Dabos

Nelson²,

Hewage

et al. 2004

Cell Transplant

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Primary hepatocytes have extensively been used in biochemical, pharmacological, and physiological research. Recently, primary porcine hepatocytes have been regarded as the cells of choice for bioartificial liver support systems. The optimum culture medium for hepatocytes to be used in such devices has yet to be defined. In this study we investigated the effectiveness of four culture media in driving energy metabolism of primary porcine hepatocytes. The media selected were William's E medium, medium 1640, medium 199, and hepatocyte medium. Cells (3 × 10 10 ; viability 87 ± 6%) were isolated from weanling piglets and seeded on 90-mm plates in the above media supplemented with antibiotics and hormones at a density of 8 × 10 6 viable cells per plate. Using 1 H NMR spectroscopy we looked at indices of glycolysis, gluconeogenesis, ketogenesis, and ureagenesis on days 2, 4, and 6 of the experiments (n = 9). We also studied urea and albumin synthesis and total P450 content. The examined metabolic pathways of the hepatocytes were maintained by all media, although there were statistically significant differences between them. All media performed well in glycolysis, ureagenesis, and albumin synthesis. William's E medium and medium 199 outperformed the rest in gluconeogenesis. Medium 199 was best in ketogenesis. Overall, medium 199 was the best at driving energy metabolism from its constituent substrates and we think that it preferentially should be used in the culture of primary porcine hepatocytes.

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Improvement of serum amino acid profile in hepatic failure with the bioartificial liver using multicellular hepatocyte spheroids

Cited by 29 publications

References 14 publications

Bioartificial Liver Inoculated with Porcine Hepatocyte Spheroids for Treatment of Canine Acute Liver Failure Model

Bioartificial Liver Inoculated with Porcine Hepatocyte Spheroids for Treatment of Canine Acute Liver Failure Model

Multicellular spheroids: a three‐dimensionalin vitroculture system to study tumour biology

Comparison of Bioenergetic Activity of Primary Porcine Hepatocytes Cultured in Four Different Media

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