It is estimated that more than three million Canadians have chronic liver disease and the incidence of some forms is increasing dramatically. Although treatments exist for the early stages of disease, progression to liver failure requires transplantation of a new organ. As the demand for transplantation far exceeds the number of available donor organs, only a limited number of patients will receive this treatment. The regeneration and repair of damaged and diseased livers through transplantation of new liver cells made from human pluripotent stem cells (hPSCs) offers a potential new therapy to treat these patients.
The McEwen Institute’s liver regeneration program is directed by Dr. Shinichiro Ogawa in collaboration with Dr. Gordon Keller. By translating knowledge of human liver development to the differentiation cultures, he has identified the regulatory pathways that promote the development of two of the main cell types in the liver-hepatocytes and cholangiocytes (bile duct cells)-from hPSCs. The cells generated under these conditions display many characteristics and properties of hepatocytes and cholangiocytes found in the adult organ. Based on these advances, it has been possible to establish differentiation protocols that promote the efficient development of both cell types in culture. With access to the hPSC-derived hepatocytes, we have begun transplantation experiments using mice engineered to undergo liver failure as pre-clinical studies to determine if it is possible to restore liver function with this approach. Our studies using the hPSC-derived cholangiocytes are focused on developing models to study Cystic Fibrosis liver disease (CFLD) that impairs the function of the bile ducts in the liver. Using this model, it is possible to establish high throughput screens to identify new drugs to treat CFLD. In addition to the hepatocytes and cholangiocytes, the liver contains a number of other cell types including immune cells, stellate cells and sinusoidal endothelial cells that play important roles in normal liver function and in liver disease. Given this, it will be important to be able to generate all of these cell types from hPSCs to develop cell-based therapies to treat a broad range of diseases.
Current projects in include: