Promising Resources of Hepatic Progenitor Cells

Abstract

Allogeneic liver transplantation remains the only effective treatment available to patients with liver failure. Because of a serious shortage of liver donors, however, an alternative therapeutic approach is urgently needed. It would be beneficial if we could obtain functional hepatocytes from nonhepatic sources to utilize for cell transplantation. Embryonic stem (ES) cells and umbilical cord blood (UCB) cells may have advantages as grafts for cell transplantation, because of their immaturity and plasticity. In contrast to their hematopoietic and mesenchymal potential, it remains unclear whether these cells function as endodermal epithelial cells. Here, with a view to utilizing ES cells and UCB cells for cell transplantation into injured liver, we investigated the hepatic potential of these types of cells both in vitro and in vivo. In the experiments with ES cells, mouse ES-derived embryoid bodies (EBs) cells were shown to contain functional hepatocytes, displaying a capacity to synthesize urea in vitro. After EB cells were transplanted relatively early in their differentiation in vitro, even before expressing hepatocyte phenotypes, they continued to differentiate into functional hepatocytes in vivo. In the experiments with UCB cells, human UCB cells proliferated and gave rise to hepatocyte-lineage cells in our original primary culture system. Also, human UCB-derived cells displayed the capacity to differentiate into functional hepatocytes in the liver after cell transplantation. In conclusion, this study demonstrates that ES cells and UCB cells could be promising resources of transplantable hepatic progenitor cells. Our findings may have relevance to the clinical application of ES-derived or UCB-derived cell transplantation as a novel therapeutic option for liver failure.