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

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. [email protected] 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 (

Nomenclature of the finer branches of the biliary tree: Canals, ductules, and ductular reactions in human livers

The work of liver stem cell biologists, largely carried out in rodent models, has now started to manifest in human investigations and applications. We can now recognize complex regenerative processes in tissue specimens that had only been suspected for decades, but we also struggle to describe what we see in human tissues in a way that takes into account the findings from the animal investigations, using a language derived from species not, in fact, so much like our own. This international group of liver pathologists and hepatologists, most of whom are actively engaged in both clinical work and scientific research, seeks to arrive at a consensus on nomenclature for normal human livers and human reactive lesions that can facilitate more rapid advancement of our field. (HEPATOLOGY 2004; 39:1739–1745.) The fine detail of normal liver microanatomy is not well understood.1, 2 This is true whether discussing hepatic vasculature, bile ducts, stroma and matrix, innervation, or lymphatics. Some points are known, but gaps remain. The distal branches of the biliary tree are reasonably well defined: the common bile duct arises from confluence of the right and left hepatic ducts, which arise from segmental ducts, which arise from septal ducts arising from interlobular ducts.3 It is known that these interlobular ducts arise from still smaller cholangiocyte-lined structures and that the lumina of these in turn are in structural continuity with the lumen of hepatocellular bile canaliculi. But the terms used for these smallest, most proximal structures have been confusing