Liver stem cells

Abstract

The liver is an essential organ for life, serving as the center for metabolism and playing various critical functions in controlling systemic homeostasis. Among multiple types of cells comprising the liver, hepatocytes and cholangiocytes are the two epithelial cell lineages in the organ, and commonly originate from hepatoblasts during organogenesis in developing embryos. Thus, hepatoblasts possess bi-lineage differentiation potential into hepatocytes and cholangiocytes, a phenotypic feature that can best distinguish and define liver stem cells. While the liver is considered not to rely on any resident stem cell population for their homeostatic maintenance, facultative stem/progenitor cells with bi-lineage differentiation potential, referred to as oval cells in rodents, may emerge under severe damage conditions and play critical roles in promoting the regenerative processes. However, the extent to which these putative stem/progenitor cells contribute to regeneration has been debated, as recent studies have shown that most regenerative responses are hepatocyte- derived, particularly in mice. Evidence for both scenarios will be discussed in later sections. Nevertheless, identification of specific markers has enabled researchers to isolate and characterize these fetal and adult stem/progenitor cell populations. In vitro culture systems as well as in vivo studies using animal models have allowed elucidation of detailed molecular mechanisms, including intercellular signaling webs and intracellular transcriptional regulatory networks, which coordinately regulate development, differentiation and behavior of these cells. Understanding the cellular and molecular basis of liver development and regeneration from the perspective of the embryonic and adult stem/progenitor cells should make invaluable contributions to future development of technologies to produce fully functional hepatocytes in vitro that are applicable for cell therapy and pharmaceutical screening.