Some patients with life-threatening liver disease can be effectively treated with liver transplantation. However, this requires a major surgical procedure that is associated with considerable morbidity and mortality. More importantly, the long-standing shortage of donor livers has rendered this treatment unavailable to most patients. Consequently, thousands of patients with end-stage liver disease die each year while on a waiting list for liver transplantation, and tens of thousands are never put on this list. Since human embryonic stem cells replicate virtually indefinitely in culture, these cells, if differentiated into liver cells (hepatocytes), represent an infinite source of cells that can be made available to treat patients with liver failure.
The objective of this award than is to develop a reproducible and efficient differentiation method to produce metabolically active human embryonic stem cell-derived hepatocytes. The initial requirement is that at least 90-95% of the cells must have liver-specific gene expression and possess metabolic function comparable to freshly isolated human hepatocytes. In addition, the yield from differentiation should be adequate to support preclinical studies. We believe that we made excellent progress during the grant award period towards meeting the success criteria for the quality of the cells in in vitro analysis. We firmly believe that our cells represent an exceedingly good level of hepatocyte function in culture, and that the remaining tasks are to scale-up their production and to determine a strategy to enhance their in vivo function.