Chapter 15 - Stellate Cell Depletion Models

Oakley, F; Mann, DA

doi:10.1016/B978-0-12-800134-9.00015-4

Chapter 15 - Stellate Cell Depletion Models

Lookup NU author(s): Professor Fiona Oakley ORCiD, Professor Derek Mann

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Abstract

© 2015 Elsevier Inc. All rights reserved. Hepatic stellate cells (HSCs) play a central role in regulating normal liver wound healing. In response to liver injury, HSCs transdifferentiate into activated hepatic myofibroblasts (HMs) and synthesize a temporary scar matrix. Collagenous fibers provide a scaffold for hepatocytes to repopulate during tissue regeneration. Once normal organ function is restored, HMs undergo apoptosis and the scar is remodeled. In chronic liver disease regardless of etiology (viral infection, autoimmune, toxic injury, metabolic, or alcohol induced) HMs persist. Under these conditions HMs become highly proliferative, migratory, contractile cells that continuously deposit extracellular matrix that drives the fibrotic changes associated with chronic liver disease. HM clearance by either apoptosis or promoting their quiescence is linked with fibrolysis, therefore depleting HMs is an attractive therapeutic strategy. We will compare the different experimental approaches used to deplete HMs or genetically modulate their function and discuss how they advance our current understanding of the mechanistic basis of liver fibrosis.