Induced Pluripotent Stem Cells as a Source of Hepatocytes

During the past decade, a series of discoveries has established the potential of the so-called terminally differentiated cells to transition to more primitive progenitor cells. The dramatic demonstration of the ability to reprogram differentiated somatic cells to induced pluripotent stem cells (iPSC) that can then give rise to cells of all three germ layers has opened the possibility of generating virtually any cell type in culture, from any given individual. Taking advantage of these concepts, researchers have generated iPSC by reprogramming a wide variety of somatic cells. In addition to their practical implications, these studies have provided crucial insights into the mechanism of cell plasticity that underlies the transition from one cell type to another. Using concepts derived from research on embryological development, investigators have differentiated iPSC to cells resembling hepatocytes in many ways. Such hepatocyte-like cells could be of enormous value in disease modeling, drug discovery and regenerative medicine. However, the currently available methods do not yield cells that fully reproduce the characteristics of adult primary hepatocytes. Thus, generating hepatocytes from iPSC is very much a work in progress. In addition to chronicling these exciting developments, this review will discuss the emergent new approaches to generating iPSC, improving their differentiation to hepatocyte-like cells, and maintaining the hepatocyte-like cells in culture for longer survival and better function.