On hepatic stem cells and their role in chronic liver disease and carcinogenesis

Hopkins, Laurence Joseph (2014). On hepatic stem cells and their role in chronic liver disease and carcinogenesis. University of Birmingham. Ph.D.

This is the latest version of this item.

Preview

Hopkins14PhD.pdf
PDF - Accepted Version
Download (6MB)

Abstract

Hepatic stem cells are found in the liver at all stages of development, including adult, and have the potential to give rise to daughter cells of biliary, hepatocytic and pancreatic lineages. Hepatic stem cells contribute significantly to liver regeneration, but may be associated with development of primary liver cancer, and are being investigated as a cellular therapy for liver failure.

This thesis describes the development of methods for the immunohistochemical quantification of hepatic stem cell activation, allowing assessment of the association between hepatic stem cell activation in needle biopsy tissue and subsequent development of HCC in a retrospectively identified cohort of cirrhotic patients. A murine dietary model of NASH and HCC was developed and characterised in detail demonstrating progressive hepatic stem cell activation with increasing injury severity. We then went on to describe and prospectively isolate a resident population of stromal stem/progenitor cells in adult, uninjured mouse liver with the potential to give rise to both myofibroblasts, and under selective conditions, epithelial stem/progenitor cells. Finally, we demonstrated the isolation of hepatic stem cell from explanted cirrhotic liver and normal common bile duct and assessed their utility as a source of hepatic stem cells for cellular or regenerative therapy.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):