Hepatocyte transplantation and bioartificial liver (BAL) as alternatives to liver transplantation offer the possibility of effective treatment for many inherited and acquired hepatic disorders. Unfortunately, the limited availability of donated livers and the variability of their derived hepatocytes make it difficult to obtain enough viable human hepatocytes for the hepatocyte-based therapies. Embryonic stem cells (ESCs), which could be isolated directly from the blastocyst inner cell mass, have permanent self-renewal capability and developmental pluripotency and therefore might be an ideal cell source in the treatment of hepatic discords. However, differentiation of hESCs into hepatocytes with significant numbers remains a challenge. This review updates our current understanding of differentiation of ESCs into hepatic lineage cells, their future therapeutic uses and problems in liver regeneration. embryonic stem cell, hepatocyte, differentiation, liver regeneration Liver is the largest organ in mammals and it exerts a variety of important functions, including metabolizing diverse dietary molecules, storing glycogen, detoxifying compounds and swallowing for defense. This organ also has hematopoietic function in embryonic/fetal stage. Since liver has so many pivotal roles, patients with acute hepatic failure or end-stage liver diseases are in great danger. Orthotopic liver transplantation remains the most successful treatment for many cases of end-stage liver disease. However, the efficacy of liver transplantation is limited by the shortage of available donor organs, risk of rejection, infections, and other complications caused by the lifelong immunosupression. Liver cell therapies, including hepatocyte transplantation and bioartificial liver (BAL), are considered promising new approaches to treatment of patients with end-stage liver disease. However, the usage of mature hepatocytes is also hampered by limited tissue source and inability to proliferate and maintain the function for a long term in vitro. Embryonic stem cells (ESCs) might serve as an ideal source for cell therapy because of their immortalization and unique ability to give rise to all somatic cell lineages. ESCs were first isolated from mouse embryos in 1981 [1] , and the establishment of the first human ESC line in 1998 [2] undoubtedly further expanded the potential of ESCs not only as an important tool for basic research but also as a promising source for cell therapy.
Today, liver transplantation (LT) is the only established treatment for end-stage liver diseases. The development of LT, including OLT, cadaveric LT, split LT, living donor LT (LDLT), brings hopes to patients with these diseases. However, increasing donor shortage, rejection and life-long immunosuppression with its side effects are the major limitations of this therapy strategy. Bone marrow-derived stem cells (BMDSCs) are capable of differentiating into hepatocyte-like cells and contribute to liver injury repair. The microenvironment of liver injury caused by rejection, ischemia/reperfusion, loss of liver mass, recurrence of HCV and "small-for-size syndrome" after LT can attract a variety of bone marrow-derived stem cell population to the peripheral circulation and then migration to the injury liver to promote the hepatic function restoration. Additionally, BMDSCs can also take part in the functional regeneration of living donor liver after LDLT. This participation in liver regeneration may be associated to the interaction between SDF-1and its receptor CXCR4, involving HGF, IL-8, MMP9, and VEGF/VEGFR-2. BMDSC with its bio-characteristics could maintain the allograft tolerance from different angles and in different ways. In conclusion, BMDSCs transplantation, as a new assistant therapeutic method for LT, will expand the space of LT, and provide more survival opportunities for the patients suffering liver diseases in the future. stem cell, plasticity, liver transplantation, liver regeneration Today, end-stage liver diseases caused by virus, toxic injury, inherited metabolic liver diseases are threatening human health seriously. Liver transplantation (LT) is the only established treatment strategy for these diseases. The development of LT, including OLT, cadaveric LT, split LT, living donor LT (LDLT), has brought hope to patients with liver diseases since Starzl first performed orthotopic liver transplantation (OLT) successfully in 1963 [1,2] . More than 50000 patients have benefited from LT worldwide with an actuarial 1-, 3-, 5-year survival of 90%, 80%, and 70% respectively [1] . However, increasing donor shortage and side effects of life-long immunosuppression set a hurdle for the appliacion of this therapy strategy. It was reported that 10%-15% of patients lost their life during their waiting for the LT per year [2] . Continuing immunosuppression increases the incidence of infection in recipients. The recurrence of hepatocellular cancer (HCC) and Hepatitis C (HCV) after LDLT are also associated with life-long immunosuppression [3,4] .During the last few years, stem cells became one of the most exciting areas of biomedical research all over the world. It is accepted that adult stem cells, which reside in many different tissues of mammal, are capable of generating many different types of tissue cells by choosing multiple differentiation pathways. That prop-
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