Signaling networks in hepatic oval cell activation

Erker, Laura; Grompe, Markus

doi:10.1016/j.scr.2008.01.002

Cited by 53 publications

(51 citation statements)

References 81 publications

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“…While several secreted molecules that participate in the LPC response have been reported (Erker and Grompe 2007), their possible involvement as niche signals has not been explored. This study provides compelling evidence that Thy1 + periportal cells form the niche for LPCs by residing in close proximity to LPCs and producing a key regulatory factor, FGF7.…”

Section: Discussionmentioning

confidence: 99%

FGF7 is a functional niche signal required for stimulation of adult liver progenitor cells that support liver regeneration

et al. 2013

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The liver is a unique organ with a remarkably high potential to regenerate upon injuries. In severely damaged livers where hepatocyte proliferation is impaired, facultative liver progenitor cells (LPCs) proliferate and are assumed to contribute to regeneration. An expansion of LPCs is often observed in patients with various types of liver diseases. However, the underlying mechanism of LPC activation still remains largely unknown. Here we show that a member of the fibroblast growth factor (FGF) family, FGF7, is a critical regulator of LPCs. Its expression was induced concomitantly with LPC response in the liver of mouse models as well as in the serum of patients with acute liver failure. Fgf7-deficient mice exhibited markedly depressed LPC expansion and higher mortality upon toxin-induced hepatic injury. Transgenic expression of FGF7 in vivo led to the induction of cells with characteristics of LPCs and ameliorated hepatic dysfunction. We revealed that Thy1 + mesenchymal cells produced FGF7 and appeared in close proximity to LPCs, implicating a role for those cells as the functional LPC niche in the regenerating liver. These findings provide new insights into the cellular and molecular basis for LPC regulation and identify FGF7 as a potential therapeutic target for liver diseases.

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Section: Discussionmentioning

confidence: 99%

FGF7 is a functional niche signal required for stimulation of adult liver progenitor cells that support liver regeneration

et al. 2013

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“…are not yet fully understood [84,85]. Given the multifunctional role assigned to BMP signaling during early liver development, including hepatic specification and liver morphogenesis, a potential role for BMP in oval cell activation, expansion and differentiation should be considered.…”

Section: Role Of Bmps In Liver Developmentmentioning

confidence: 99%

BMPS and Liver: More Questions than Answers

Herrera¹,

Sánchez²,

Fabregat³

2012

Current Pharmaceutical Design

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“…38,45 Other investigators suggest that they are the progeny of a hepatic stem cell, also referred to as adult liver stem cells. 45,59 The mechanisms by which these cells are activated to proliferate and differentiate during liver regeneration is important for the development of new therapies to treat liver disease. 59 Hepatic oval cell activation, proliferation, and differentiation has been observed under certain physiological conditions, mainly when the proliferation of existing hepatocytes has been inhibited as a consequence of a severe hepatic injury.…”

Section: Hepatic Oval Stem Cells Are Bipotent Stem Cellsmentioning

confidence: 99%

“…45,59 The mechanisms by which these cells are activated to proliferate and differentiate during liver regeneration is important for the development of new therapies to treat liver disease. 59 Hepatic oval cell activation, proliferation, and differentiation has been observed under certain physiological conditions, mainly when the proliferation of existing hepatocytes has been inhibited as a consequence of a severe hepatic injury. 60 In addition to the effects seen in the liver, oval cells or oval like-cells are implicated in the architecture of the regenerated pancreas after injury 61,62 and they may be involved in the regeneration of other organs as well.…”

Section: Hepatic Oval Stem Cells Are Bipotent Stem Cellsmentioning

confidence: 99%

Pluripotent plasticity of stem cells and liver repopulation

Gennero

Roos

Sperber

et al. 2010

Cell Biochemistry & Function

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Different types of stem cells have a role in liver regeneration or fibrous repair during and after several liver diseases. Otherwise, the origin of hepatic and/or extra-hepatic stem cells in reactive liver repopulation is under controversy. The ability of the human body to self-repair and replace the cells and tissues of some organs is often evident. It has been estimated that complete renewal of liver tissue takes place in about a year. Replacement of lost liver tissues is accomplished by proliferation of mature hepatocytes, hepatic oval stem cells differentiation, and sinusoidal cells as support. Hepatic oval cells display a distinct phenotype and have been shown to be a bipotential progenitor of two types of epithelial cells found in the liver, hepatocytes, and bile ductular cells. In gastroenterology and hepatology, the first attempts to translate stem cell basic research into novel therapeutic strategies have been made for the treatment of several disorders, such as inflammatory bowel diseases, diabetes mellitus, celiachy, and acute or chronic hepatopaties. In the future, pluripotent plasticity of stem cells will open a variety of clinical application strategies for the treatment of tissue injuries, degenerated organs. The promise of liver stem cells lie in their potential to provide a continuous and readily available source of liver cells that can be used for gene therapy, cell transplant, bio-artificial liver-assisted devices, drug toxicology testing, and use as an in vitro model to understand the developmental biology of the liver.

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Signaling networks in hepatic oval cell activation

Cited by 53 publications

References 81 publications

FGF7 is a functional niche signal required for stimulation of adult liver progenitor cells that support liver regeneration

FGF7 is a functional niche signal required for stimulation of adult liver progenitor cells that support liver regeneration

BMPS and Liver: More Questions than Answers

Pluripotent plasticity of stem cells and liver repopulation

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