FGF signaling segregates biliary cell‐lineage from chick hepatoblasts cooperatively with BMP4 and ECM components in vitro

Yanai, Masaaki; Tatsumi, Norifumi; Hasunuma, Noboru; Katsu, Kenjiro; Endo, Fumio; Yokouchi, Yuji

doi:10.1002/dvdy.21520

Cited by 60 publications

(47 citation statements)

References 66 publications

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“…Presumably, it is some aspect of cell-to-cell interaction that is critical for induction of multicellular bile ductule formation by the PICM-19 cells. The feeder-independent culture, therefore, provides an experimental platform from which to investigate what factors may be important in inducing duct formation by PICM-19 cells, such as the interplay of elevated culture pH (Talbot et al 2002), matrix interactions (Yanai et al 2008), and HGF levels (Montesano et al 1991a, b). Without the presence of the feeder cells, the reliance of the PICM-19 cell culture on STO conditioned medium can be examined.…”

Section: Discussionmentioning

confidence: 99%

Feeder-independent continuous culture of the PICM-19 pig liver stem cell line

Talbot

Blomberg

Garrett

et al. 2010

In Vitro Cell.Dev.Biol.-Animal

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The PICM-19 pig liver stem cell line is a bipotent cell line, i.e., capable of forming either bile ductules or hepatocyte monolayers in vitro, that was derived from the primary culture of pig embryonic stem cells. The cell line has been strictly feeder-dependent in that cell replication, morphology, and function were lost if the cells were cultured without STO feeder cells. A method for the feeder-independent continuous culture of PICM-19 cells (FI-PICM-19) is presented. PICM-19 cells were maintained and grown without feeder cells on collagen I-coated tissue culture plastic for 26 passages (P26) with initial split ratios of 1:3 that diminished to split ratios of less than 1:2 after passage 16. Once plated, the FI-PICM-19 cells were overlaid with a 1:12 to 1:50 dilution of Matrigel or related extracellular matrix product. Growth of the cells was stimulated by daily refeedings with STO feeder-cell conditioned medium. The FI-PICM-19 cells grew to an approximate confluence of 50% prior to each passage at 2-wk intervals. Growth curve analysis showed their average cell number doubling time to be ~96 h. Morphologically, the feeder-independent cells closely resembled PICM-19 cells grown on feeder cells, and biliary canalicui were present at cell-to-cell junctions. However, no spontaneous multicellular ductules formed in the monolayers of FI-PICM-19 cells. Ultrastructural subcellular features of the FI-PICM-19 cells were similar to those of PICM-19 cells cultured on feeder cells. The FI-PICM-19 cells produced a spectrum of serum proteins and expressed many liver/hepatocyte-specific genes. Importantly, cytochrome P450 (EROD) activity, ammonia clearance, and urea production were maintained by the feeder-independent cells. This simple method for the propagation of the PICM-19 cell line without feeder cells should simplify the generation and selection of functional mutants within the population and enhances the cell line's potential for use in toxicological/pharmacological screening assays and for use in an artificial liver device.

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Section: Discussionmentioning

confidence: 99%

Feeder-independent continuous culture of the PICM-19 pig liver stem cell line

Talbot

Blomberg

Garrett

et al. 2010

In Vitro Cell.Dev.Biol.-Animal

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“…Given that hepatic stellate cells also express jagged 1 (66), it will be interesting to investigate whether they modulate biliary cell development via Notch signaling. Alternatively, hepatic stellate cells could influence hepatoblast differentiation through production of ECM proteins, as different ECM components have different effects on the determination of the hepatocyte and biliary cell fate (67,68).…”

Section: Hepatic Stellate Cells In Liver Developmentmentioning

confidence: 99%

Hepatic stellate cells in liver development, regeneration, and cancer

Yin¹,

Evason²,

Asahina³

et al. 2013

J. Clin. Invest.

602

567

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Hepatic stellate cells are liver-specific mesenchymal cells that play vital roles in liver physiology and fibrogenesis. They are located in the space of Disse and maintain close interactions with sinusoidal endothelial cells and hepatic epithelial cells. It is becoming increasingly clear that hepatic stellate cells have a profound impact on the differentiation, proliferation, and morphogenesis of other hepatic cell types during liver development and regeneration. In this Review, we summarize and evaluate the recent advances in our understanding of the formation and characteristics of hepatic stellate cells, as well as their function in liver development, regeneration, and cancer. We also discuss how improved knowledge of these processes offers new perspectives for the treatment of patients with liver diseases.

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“…Several FGFR2b ligands are implicated in developing livers, including FGF1, FGF7, and FGF10. In vitro studies have shown that FGF1 enriches bipotential hepatic progenitor cells, whereas FGF7 promotes differentiation of biliary epithelial cells (BECs) in cultured embryonic livers [5,6]. Expression of FGF10 in hepatic stellate cells (HSCs) is crucial for the developing liver by maintaining survival of hepatoblasts through FGFR2b receptor [4].…”

Section: Introductionmentioning

confidence: 99%

Expression and Function of Fibroblast Growth Factor (FGF) 7 during Liver Regeneration

Tsai

Wang

2011

Cell Physiol Biochem

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Background/Aim: Previous studies have shown that fibroblast growth factors (FGFs) are involved in the process of liver injury repair. Liver regeneration after partial hepatectomy (PH) is impaired in transgenic mice expressing dominant-negative FGFR2b in hepatocytes. Although FGF7, a ligand specifically bound to FGFR2b, is expressed by activated hepatic stellate cells (HSCs) in fibrotic livers, the expressions and functions of FGF7 and FGFR2b after PH remain unexplored. Therefore, this study sought to examine the potential role of FGF7 signaling during liver regeneration. Methods: We examined the expression of FGF7 and FGFR2b in normal and regenerating livers. Effects of FGF7 on hepatocytes were examined in vitro using primary hepatocyte culture with FGF7 recombinant protein and in vivo by hydrodynamic-based gene transfer method. Results: We found that FGF7 expression was increased according to the activation status of HSCs after PH. The receptor, FGFR2b, was also increased in hepatocytes during liver regeneration. In vitro treatment with FGF7 protein activated ERK1/2 and promoted proliferation of hepatocytes isolated from regenerating livers. In vivo overexpression of exogenous FGF7 could notably promote hepatic proliferation and activate MAPKs after PH. Conclusion: This study suggests a role for activated HSC-expressed FGF7 in stimulating FGF signaling pathways in hepatocytes and regulating liver regeneration.

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FGF signaling segregates biliary cell‐lineage from chick hepatoblasts cooperatively with BMP4 and ECM components in vitro

Cited by 60 publications

References 66 publications

Feeder-independent continuous culture of the PICM-19 pig liver stem cell line

Feeder-independent continuous culture of the PICM-19 pig liver stem cell line

Hepatic stellate cells in liver development, regeneration, and cancer

Expression and Function of Fibroblast Growth Factor (FGF) 7 during Liver Regeneration

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