Developments in bioartificial liver research: concepts, performance, and applications

Nagamori, Seishi; Hasumura, Satoshi; Matsuura, Tomokazu; Aizaki, Hideki; Kawada, Masayuki

doi:10.1007/s005350070071

Cited by 46 publications

(27 citation statements)

References 66 publications

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“…In this study, fetal porcine hepatic cells with proliferative capacity were cultured in a RFB system that allowed highdensity, three-dimension culture [1][2][3][4] , and the usefulness of the RFB system as a BAL and the possibility of liver reconstruction with implantable organoids were examined. Although the high proliferative capacity of embryonic cells is well known, it has been unclear at which gestational age the fetal liver cells show optimal proliferation and functional capacity when used as a source of cells for a BAL or for organoid reconstruction.…”

Section: Discussionmentioning

confidence: 99%

“…In consideration of the results of oxygen consumption and morphological features, the NH3 loading test compared the HFE35 group, FME35 group, and HFE56 group. After incubation for one week (d 7) in the RFB, ammonium chloride (NH4Cl) was added at three concentrations (1 mmol/L + 2 mmol/L + 3 mmol/L) every 8 h for 24 h, followed by 3 mmol/L for a further 24 h [4] . Then NH3 and urea levels were measured on d 8 and d 9 using an automatic high-speed amino acid analyzer JLC-300 (JEOL Ltd., Tokyo).…”

Section: Ammonia Loading Testmentioning

confidence: 99%

“…We have developed a radial flow bioreactor (RFB), which is a 3-dimensional culture system that can be used for high-density culture [1][2][3][4] , achieving a cell density 10 times greater than that obtained with hollow-fiber culture [5,6] . A cylindrical bioreactor is filled with porous cellulose beads that act as microcarriers, and culture medium flows from the periphery toward the center of the reactor ( Figure 1A) [2,7] .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hepatic reconstruction from fetal porcine liver cells using a radial flow bioreactor

Ishii¹,

Saito²,

Marushima³

et al. 2008

WJG

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Section: Discussionmentioning

confidence: 99%

Section: Ammonia Loading Testmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hepatic reconstruction from fetal porcine liver cells using a radial flow bioreactor

Ishii¹,

Saito²,

Marushima³

et al. 2008

WJG

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“…Use of an RFB (RA-15, ABLE Co., Ltd., Tokyo, Japan) and mass flow controller (RAD925, ABLE Co., Ltd.) has previously been reported for the high-density, 3-dimensional mass production of cells, which attach to a matrix. 12,13 The matrix consisted of hydroxy apatite beads (diameter 1-2 mm, pore size Ͻ200 m, Asahi Optical Co., Ltd., Tokyo, Japan), with a high pore density, which gave a wide surface attachment area.…”

Section: Methodsmentioning

confidence: 99%

CYP3A4 inducible model for in vitro analysis of human drug metabolism using a bioartificial liver

Iwahori

2003

Hepatology

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CYP3A is responsible for approximately 50% of the therapeutic drug-metabolizing activity in the liver. The present study was undertaken to establish the CYP3A4 inducible model for analysis of human drug metabolism using a bioartificial liver composed of the functional hepatocellular carcinoma cell (HCC) line FLC-5. A radial-flow bioreactor (RFB), which is a carrier-filled type bioreactor, was used for 3-dimensional perfusion culture of FLC-5 cells. The CYP3A4 messenger RNA (mRNA) expression level 48 hours after rifampicin treatment in the RBF was approximately 100 times higher than that in a monolayer culture. Western blot analysis also demonstrated an increase in expression of the CYP3A protein. When testosterone, a substrate for CYP3A4, was added to the rifampicin-treated cell culture, 6␤-hydroxy testosterone as a metabolite was formed. D rug-drug interactions can be categorized as mediated by metabolic inhibition and enzyme induction. Numerous studies have been conducted on metabolic inhibition. It is now possible, to some extent, to predict drug-drug interactions in vivo based on the results in vitro. Enzyme induction has been studied using experimental animals, but, because of the existence of interspecies differences, it is often difficult to extrapolate the results of animal studies directly to humans. 1 To resolve these problems, enzyme-induction experiments have been performed using human primary cell culture systems, and experimental models established using these cell cultures have been recognized to be useful in the evaluation of enzyme induction. 2 However, longterm primary culture of human hepatocytes can reduce the functions of liver enzymes, as reflected, for example, by a decrease in the level of cytochrome P450 (CYP), an enzyme mainly catalyzing phase-I reactions of drug metabolism, 4 days after isolation, making it difficult to use these cells for prolonged periods of time. 3 Furthermore, because of interracial or sex-related differences and differences in storage periods (cell viability), the drug-metabolizing activity varies greatly among cells, causing problems in reproducibility. 4,5 For these reasons, much has been expected of liver cell lines that have uniform and stable properties, can be used for long-term experiments, are highly differentiated, and retain human liver functions.

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“…FLC4 (Nagamori et al, 2000) was a gift from Dr Seishi Nagamori. HuH1, HuH4 and HuH7 were obtained from the Japanese Culture Collection.…”

Section: Cell Lines and Tissue Samplesmentioning

confidence: 99%

Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma

et al. 2005

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We identified that suppressor of cytokine signaling-3 (SOCS-3) gene was aberrantly methylated in its CpG island in three of 10 human hepatocellular carcinoma (HCC) cell lines. SOCS-3 RNA was undetectable in five of the 10 HCC cell lines including the three methylated cell lines, and a demethylating agent, 5-aza-2 0 -deoxycytidine, reactivated SOCS-3 expression in three cell lines tested. The DNA region where we found aberrant DNA methylation includes a signal transducers and activators of transcription (STAT) binding consensus sequence. When the DNA region was used as a promoter, DNA methylation markedly reduced promoter activity. SOCS-3 was also aberrantly methylated in six of 18 primary HCC samples. SOCS-3 expression was reduced in three of the three methylated and one of the three unmethylated primary samples examined. Restoration of SOCS-3 in cells lacking SOCS-3 expression suppressed STAT3 phosphorylation and cell growth. We found that IL-6 acted as a growth factor in HCC cells. Inhibition of SOCS-3 expression in cells whose growth was induced by IL-6 enhanced STAT3 phosphorylation and cell growth. In addition, AG490, a chemical JAK2 inhibitor, suppressed cell growth and downregulated STAT3 phosphorylation, but not FAK phosphorylation. We also found that SOCS-3 physically interacted with phosphorylated FAK and Elongin B in HCC cells. Restoration of SOCS-3 decreased FAK phosphorylation as well as FAK protein level. Inhibition of SOCS-3 expression increased FAK phosphorylation, resulting in enhancement of cell migration. These data indicate that SOCS-3 negatively regulates cell growth and cell motility by inhibiting Janus kinase (JAK)/STAT and FAK signalings in HCC cells. Thus, loss of SOCS-3 by the associated DNA methylation confers cells advantage in growth and migration.

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Developments in bioartificial liver research: concepts, performance, and applications

Cited by 46 publications

References 66 publications

Hepatic reconstruction from fetal porcine liver cells using a radial flow bioreactor

Hepatic reconstruction from fetal porcine liver cells using a radial flow bioreactor

CYP3A4 inducible model for in vitro analysis of human drug metabolism using a bioartificial liver

Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma

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