Characterisation of novel cell surface-reactive markers for identifying and isolating liver and pancreas progenitor cells

[Truncated] The use of renewable stem cell populations to generate hepatocytes and β-cells for therapy is a beguiling prospect to overcome the challenge of limited supply of donor organs used to treat end-stage liver disease and Type 1 Diabetes. Although progress towards this goal has been significant, generating mature cells in vitro, and overcoming the potential tumourigenicity of stem cells, are problems which must be addressed before the promise of stem-cell based therapies can be translated from the laboratory to the clinic. Understanding the mechanisms involved in expansion, differentiation and transformation are therefore vital. The liver and pancreas share both a common origin and developmental mechanisms, so studying their development in parallel should help make progress towards the goal of cell based therapies.

The ability to study the biology of liver and pancreas progenitors is currently hampered by a lack of markers to identify and isolate their progenitors. To help overcome this problem, the goals of my project were to (i) develop novel cell surface-reactive monoclonal antibodies marking liver and pancreas progenitors; (ii) to characterise the ability of these antibodies for identifying and isolating liver and pancreas progenitor cells; and (iii) to identify protein targets of useful antibodies in order to facilitate translational and functional studies. A panel of monoclonal antibodies, termed ‘Western Australian Monoclonal’ (WAM) antibodies, was generated. These antibodies were specific for antigens on the cell surface of immature liver and pancreas cells. From this panel, two antibodies, WAM18 and WAM21, recognised antigens common to immature liver and pancreas cells.