Stem Cells for HUMAN Hepatic Tissue Engineering

1.1 Clinical implications End-stage liver disease is a life-threatening condition for which the only effective medical treatment available to date is orthotropic liver transplantation. Other approaches are needed because of the severe shortage of donors. These alternatives include cell transplantation and extracorporeal bioartificial livers. Since adult hepatocytes do not readily proliferate in culture, and healthy human livers are used to meet transplantation needs and are therefore not available for other purposes, a major challenge for these cell-based therapies is to identify a reliable hepatocyte source[1]. In the case of extracorporeal devices, many have suggested the use of animal sources (e.g. rat and pig), where immunoisolation may be possible. This is not likely to be a viable option for cell implantable modalities since these implants must be vascularized to function properly, and as a result would be exposed to xenogeneic immune rejection[2]. An increasingly plausible approach is the use of hepatocytes derived from embryonic stem cells (ESCs), as recent studies – reviewed in greater detail below – show that it is possible to differentiate ESCs into hepatocyte-like cells with high yields. Furthermore, recent developments with induced pluripotent stem cells (iPSCs) suggest that many of the procedures used to differentiate ESCs could be used on iPSCs, thus making it possible to derive patient-specific syngeneic hepatocytes. Besides therapeutic applications, hepatocytes derived from human ESCs can be used for a variety of other applications, such as toxicity drug screening, where the use of human cells is much preferred compared to animal cells that often vary in sensitivity and metabolism of xenobiotics and drugs.