Differentiation of Hepatocytes from Mice Embryonic Stem Cells in Three-Dimensional Culture System Imitating in vivo Environment

Abstract

Liver transplantation is accepted as the standard treatment for saving patients affected with serious liver disease. However the demand for donated livers for transplantation far exceeds the supply. One potential way to compensate for the chronic shortage is the development of bioartificial (Aoki et al., 2008, Mizumoto et al., 2004, Qian et al., 2003) and secondary livers (Kosone et al., 2008, Nguyen et al., 2009, Strom & Fisher, 2003). A necessity for development of these liver systems is the availability of sufficient high quality hepatocytes (Dan & Yeoh, 2008, Haridass et al., 2009, Mizumoto et al., 2008, Umehara et al., 2008). In addition, the high quality hepatocytes have great potentials to be source for pharmaceutical models to assess toxicity of new drugs, a critical step in drug discovery and development. In this review, we describe recent progress towards using embryonic stem (ES) cells differentiated in threedimensional (3D) culture systems that imitate in vivo environment of hepatic histogenesis and liver regeneration. We suggest that the combination of the ES cells and 3D culture systems have the potential to provide high quality hepatocytes. Pluripotent ES cells, which are derived from the inner cell mass of blastocysts, are able to replicate and differentiate into various cell types composed of whole body. Thus, ES cells have great potentials to serve as sources of hepatocytes to construct liver systems, bioartificial or secondary livers. Hepatocyte-like cells differentiated from ES cells by various methods have already been reported (Hamazaki et al., 2001, Matsumoto et al., 2008, Rambhatla et al., 2003). This review introduces our culture systems for differentiation into the hepatocyte-like cells and describes the characteristics of the ES cell-derived hepatocytelike cells induced by the culture systems.