Characterisation of the Feline Hepatic Progenitor Cell Niche

Abstract

Background/Aims: The liver has enormous regenerative capabilities. When hepatocellular proliferation is hampered the hepatic progenitor cells are activated to aid in the regeneration. The canine liver is proving to be a useful research model for hepatitis in humans. In felines the two most common liver diseases are lipidosis and cholangitis. If the HPC niche is similar to that in humans and canines the feline liver could be used as a research model for (non) alcoholic steatohepatitis and sclerosing cholangitis in humans. The hepatic progenitor cell niche in the feline was characterized in healthy liver and in livers histologically diagnosed with lipidosis, neutrophilic cholangitis and lymphocytic cholangitis. Methods: We characterized the HPC niche looking specifically for progenitor cells using CK19 marker (bile duct and HPC marker), macrophages using MAC387 marker, hepatic stellate cells/myofibroblasts using αSMA and laminin using the marker laminin. Results: We found that the feline HPC niche contains the above mentioned components and appears to be similar to the HPC niche in humans and canines. The varying degree of histologically diagnosed disease severity allowed us to view the HPC niche in different stages of disease. The presence of lipidosis or cholangitis does not always result in an activation of the HPCs. It depends on the level of liver damage and inflammation whether or not activation is necessary. We confirmed that macrophages, HSCs/myofibroblasts and laminin play an important role in the activation of the HPCs. Conclusion: As in humans and canines HPC activation is related to histological disease severity and macrophages, HSCs/myofibroblasts and laminin are important components in the HPC niche.