Cross-species immunohistochemical investigation of the activation of the liver progenitor cell niche in different types of liver disease

Abstract

Liver Int. 2009 Sep;29(8):1241-52. Epub 2009 Apr 20. Cross-species immunohistochemical investigation of the activation of the liver progenitor cell niche in different types of liver disease. Schotanus BA, van den Ingh TS, Penning LC, Rothuizen J, Roskams TA, Spee B. Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands. b.a.schotanus@uu.nl BACKGROUND: When hepatocyte replication during liver disease is insufficient for regeneration, liver progenitor cells (LPCs) are activated. The cells and stroma in the immediate environment of LPCs, together termed the LPC niche, are thought to play an important role in this activation. Among these cells are the hepatic stellate cells (HSCs)/myofibroblasts (MFs). AIMS/METHODS: We assessed the activation of HSC/MFs and LPCs in relation to the histological location and extent of liver disease in immunohistochemically (double) stained serial sections. Markers of HSC/MFs [alpha-smooth muscle actin, glial fibrillary acidic protein (GFAP), neurotrophin 3 and neural-cell adhesion molecule], markers of LPCs (keratin 7 and keratin 19) and a proliferation marker (Ki67) were used. A very relevant spontaneous model to evaluate LPC niche activation in a translational approach seems to be the dog. Therefore, both human and canine liver diseases with different degree of fibrosis and disease activity were included. RESULTS: In human and canine liver disease, type and extent of LPC niche activation depended on type and severity of disease (P