Recent advances in derivation of functional hepatocytes from placental stem cells

End-stage liver diseases are one of the leading causes of death in the world. Often orthotopic liver transplantation represents the final therapeutic choice. The limits of this approach are the scarcity of donor livers available, and the many side effects related to the administration of immune suppressants to the patients. Cellular therapy for liver diseases is increasingly being viewed as a promising strategy to provide hepatocytes to replenish the parenchymal cells of the organ. This technique suffers of some important limitations, such as the difficulty in isolating sufficient cell numbers (e.g. when adult or foetal hepatocytes are used for transplantation), the limited viability of isolated hepatocytes and, when applicable, the limited differentiation of stem cells (when hepatocyte-like cells are derived from hepatic or extra-hepatic progenitor populations). In recent years, perinatal stem cells have been proposed as reliable cellular populations which may be successfully used to derive hepatocyte-like cells. These cells feature key advantages over other adult stem cells: may be easily sourced from the tissues of origin, can be expanded ex vivo to obtain high cell numbers, may be differentiated towards hepatocyte-like cells. In addition, these cells feature relevant immunomodulatory and anti-inflammatory activities, and their sourcing is not limited by ethical concerns In the present review we analyze the molecular basis of hepatocyte biology and development, and discuss the recent advances in deriving hapatocyte-like cells from perinatal stem cells. Very recent papers on mesenchymal stem cells derived from bone marrow and adipose tissues are also comparatively discussed as prototypes of the use of adult extrahepatic stem cells. In our opinion, perinatal stem cells do represent a promising tool for liver regenerative medicine, and recent research reports further strengthened this perception and fostered further efforts by multiple research groups worldwide.