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Activation of stem cells in hepatic diseases

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Abstract

The liver has enormous regenerative capacity. Following acute liver injury, hepatocyte division regenerates the parenchyma but, if this capacity is overwhelmed during massive or chronic liver injury, the intrinsic hepatic progenitor cells (HPCs) termed oval cells are activated. These HPCs are bipotential and can regenerate both biliary epithelia and hepatocytes. Multiple signalling pathways contribute to the complex mechanism controlling the behaviour of the HPCs. These signals are delivered primarily by the surrounding microenvironment. During liver disease, stem cells extrinsic to the liver are activated and bone-marrow-derived cells play a role in the generation of fibrosis during liver injury and its resolution. Here, we review our current understanding of the role of stem cells during liver disease and their mechanisms of activation.

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Abbreviations

αFP:

Alpha-fetoprotein

AAF:

2-N-acetylaminofluorene

BDL:

Bile duct ligation

BM:

Bone marrow

BMSC:

Bone marrow stem cell

CCl4 :

Carbon tetrachloride

CDE:

Choline-deficient ethionine-supplemented

CK:

Cytokeratin

CTGF:

Connective tissue growth factor

DDC:

3,5-Diethoxycarbonlyl-1,4-dihydrocollidine-supplemented

DPPIV:

Dipeptidyl peptidase IV

ECM:

Extracellular matrix

ERK:

Extracellular signal-regulated kinase

EGF:

Epidermal growth factor

FAH −/− :

Fumarylacetoacetate hydrolase knockout

FGF:

Fibroblast growth factor

FGFR:

FGF receptor

G-CSF:

Granulocyte colony-stimulating factor

HGF:

Hepatocyte growth factor

HCC:

Hepatocellular carcinoma

HPC:

Hepatic progenitor cell

IFN:

Interferon

IL:

Interleukin

JAK:

Janus kinase

LIF:

Leukaemia inhibitor factor

LIFR:

LIF receptor

LT:

Lymphotoxin

MMP:

Metalloproteinase

OC:

Oval cell

OSM:

Oncostatin M

OSMR:

OSM receptor

PH:

Partial hepatectomy

PPAR:

Peroxisome-proliferator-activated receptor

SCF:

Stem cell factor

SDF-1:

Stromal-cell-derived factor 1

SgIGSF:

Spermatogenic immunoglobulin superfamily

STAT:

Signal transductor and activator of transcription

TGF:

Transforming growth factor

TNF:

Tumour necrosis factor

TWEAK:

TNF-like weak induction of apoptosis

uPA:

Urokinase-type plasminogen activator

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  1. MRC/University of Edinburgh Centre for Inflammation Research, The Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK

    T. G. Bird, S. Lorenzini & S. J. Forbes

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  1. T. G. Bird
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  2. S. Lorenzini
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  3. S. J. Forbes
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Correspondence to T. G. Bird.

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This work was supported by a Wellcome Trust Clinical Training Fellowship to T.G.B.; S.L. is supported by an EASL Sheila Sherlock Fellowship Post-Doctoral Fellowship.

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Bird, T.G., Lorenzini, S. & Forbes, S.J. Activation of stem cells in hepatic diseases. Cell Tissue Res 331, 283–300 (2008). https://doi.org/10.1007/s00441-007-0542-z

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