Stimulative effect of non-parenchymal liver cells on ability of tyrosine aminotransferase induction in hepatocytes

Yagi, Kiyohito; Suenobu, Noriko; Serada, Masashi; Tsuda, Kozo; Kondoh, A.; Miura, Yoshiharu

doi:10.1007/bf00376097

Cited by 10 publications

(5 citation statements)

References 26 publications

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“…We have been investigating the use of nonparenchymal liver cells (NPLCs) as well as hepatocytes with the aim of constructing a BAL system that mimics the in vivo environment to sustain liver functions in vitro. Among our results, we found that a monolayer co-culture of hepatocytes and NPLCs stimulated the induction of tyrosine aminotransferase (TAT), which is a hepatocyte-specific function (Yagi et al, 1992); microencapsulated heterospheroids consisting of hepatocytes and NPLCs maintained albumin secretion and TAT induction longer than a spheroids consisting only of hepatocytes (Yagi et al, 1993); a hierarchical co-culture in which hepatocytes and NPLCs were separated by a collagen layer also exhibited a similar stimulatory effect (Yagi et al, 1995). In the latter configuration, a soluble factor(s) was able to diffuse from the NPLCs at the bottom of the dish through the collagen layer and reach the hepatocytes without dispersing into the medium.…”

Section: Introductionmentioning

confidence: 77%

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et al. 1998

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A hierarchial co-culture, in which rat hepatocytes and non-parenchymal liver cells (NPLCs) were separated by a collagen layer and which was designed to mimic the in vivo microenvironment, was carried out with the aim of developing a module for bio-artificial liver support. Compared with a monolayer co-culture and hepatocytes cultured alone in a monolayer, higher urea synthesis activity was maintained for 6 d in the hierarchical co-culture. When a rat hepatoma cell line H4-II-E-C3, which retains the induction of tyrosine aminotransferase (TAT), was co-cultured in a monolayer with NPLCs, dose-dependent stimulation of TAT induction was observed. In a hierarchical co-culture, NPLCs further stimulated TAT induction in H4-II-E-C3 cells. Since peritoneal macrophages could stimulate TAT induction in hepatocytes in both monolayer and hierarchical co-cultures, bone marrow cells, which can proliferate and differentiate into macrophages in vitro, were investigated as a possible substitute for NPLCs. Bone marrow cells isolated from rat femurs were cultivated in the presence of IL-3 and macrophage colony-stimulating factor (M-CSF), and co-cultured with hepatocytes. Urea synthesis and TAT induction of hepatocytes were stimulated in the co-culture. The co-culture of bone marrow and H4-II-E-C3 cells, both of which have proliferation ability in vitro, was also shown to be effective in stimulating liver functions. The hierarchical configuration, in which two cell types can communicate with the soluble factor(s) through a collagen layer, was found to be more effective than a monolayer in long-term co-culture.

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Section: Introductionmentioning

confidence: 77%

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et al. 1998

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“…Why do we need mixed liver cell spheroids? Hepatocyte cultures with nonparenchymal cells have higher function than pure hepatocyte cultures (22). It has previously been shown that heterologous interaction is important for maintaining hepatocyte differentiation partly via paracrine regulations (23).…”

Section: Discussionmentioning

confidence: 99%

A Novel Method for Faster Formation of Rat Liver Cell Spheroids

et al. 2002

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Hepatocyte spheroids are expected to be the main component of the artificial liver bioreactor for their higher function. The preparation of hepatocyte spheroids, however, can require as many as 24 to 96 h. To reduce this time, we investigated a method employing a new technique of rat hepatocyte preparation and a dynamic culture. The modified Seglen's method for standard hepatocyte isolation was altered by elimination of ethyleneglycol bis(aminoethylether) tetraacetate from the first perfusate and calcium from the second perfusate. Isolated hepatocytes were cultured in a spinner flask by spinning at 120 rpm. The modified Seglen's method was used as a control. Cells obtained by the new method were more cohesive and formed a higher proportion of cell aggregates than control cells. In the spinning culture, hepatocytes had a tendency to aggregate and 80% of cells formed spheroids within 6 h of culturing. The mean size of spheroids was 68.5 +/- 18.5 microm. Confocal laser scanning microscopy revealed that individual spheroids contained approximately 30% of nonparenchymal cells over their surface. Using the new hepatocyte preparation method followed by a spinning culture, we were able to produce hepatocyte spheroids in as few as 6 h.

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“…Kupffer cell/ hepatocyte co-cultures have also been reported, exhibiting responses to a variety of inflammatory stimuli not observed in monocultures [86]. Metabolic functions are also dramatically increased when KCs are cultured with hepatocytes, as demonstrated by Yagi et al [87]. Various other immune cells have also been co-cultured with hepatocytes [23,88], such as, for example, the monocytic THP-1 cell line [89].…”

Section: D Liver Co-culturesmentioning

confidence: 95%

Three-dimensional (3D) liver cell models - a tool for bridging the gap between animal studies and clinical trials when screening liver accumulation and toxicity of nanobiomaterials

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Movia

Prina-Mello

2022

Drug Deliv. and Transl. Res.

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Despite the exciting properties and wide-reaching applications of nanobiomaterials (NBMs) in human health and medicine, their translation from bench to bedside is slow, with a predominant issue being liver accumulation and toxicity following systemic administration. In vitro 2D cell-based assays and in vivo testing are the most popular and widely used methods for assessing liver toxicity at pre-clinical stages; however, these fall short in predicting toxicity for NBMs. Focusing on in vitro and in vivo assessment, the accurate prediction of human-specific hepatotoxicity is still a significant challenge to researchers. This review describes the relationship between NBMs and the liver, and the methods for assessing toxicity, focusing on the limitations they bring in the assessment of NBM hepatotoxicity as one of the reasons defining the poor translation for NBMs. We will then present some of the most recent advances towards the development of more biologically relevant in vitro liver methods based on tissue-mimetic 3D cell models and how these could facilitate the translation of NBMs going forward. Finally, we also discuss the low public acceptance and limited uptake of tissue-mimetic 3D models in pre-clinical assessment, despite the demonstrated technical and ethical advantages associated with them. Graphical abstract 3D culture models for use as in vitro alternatives to traditional methods and conventional in vivo animal testing for testing liver accumulation and toxicity of nanobiomaterials

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Stimulative effect of non-parenchymal liver cells on ability of tyrosine aminotransferase induction in hepatocytes

Cited by 10 publications

References 26 publications

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A Novel Method for Faster Formation of Rat Liver Cell Spheroids

Three-dimensional (3D) liver cell models - a tool for bridging the gap between animal studies and clinical trials when screening liver accumulation and toxicity of nanobiomaterials

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