Human hepatocyte transplantation: state of the art. J Intern Med

Paediatric Liver Centre, King's College London School of Medicine at King's College Hospital, UK.
Journal of Internal Medicine (Impact Factor: 5.79). 10/2009; 266(4):339-57. DOI: 10.1111/j.1365-2796.2009.02152.x
Source: PubMed

ABSTRACT Hepatocyte transplantation is making its transition from bench to bedside for liver-based metabolic disorders and acute liver failure. Over eighty patients have now been transplanted world wide and the safety of the procedure together with medium-term success has been established. A major limiting factor in the field is the availability of good quality cells as hepatocytes are derived from grafts that are deemed unsuitable for transplantation. Alternative sources of cell, including stem cells may provide a sustainable equivalent to primary hepatocytes. There is also a need to develop techniques that will improve the engraftment, survival and function of transplanted hepatocytes. Such developments may allow hepatocyte transplantation to become an accepted and practical alternative to liver transplantation in the near future.

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    • "However, the availability of these cells for in vitro testing is limited (Guguen-Guillouzo and Guillouzo, 2010; LeCluyse, 2001). In addition, the quality of primary human hepatocytes is often compromised as they are usually obtained from liver biopsies of patients suffering from a liver disease or from post-mortem donated livers that are unsuitable for transplantation (Fitzpatrick et al., 2009). At present, the most plausible alternatives for primary human hepatocytes are hepatic cell lines such as HepG2 and HepaRG (Guguen-Guillouzo and Guillouzo, 2010). "
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    ABSTRACT: Besides their role in the elucidation of pathogenic processes of medical and pharmacological nature, biomarkers can also be used to document specific toxicological events. Hepatic cells generated from human skin-derived precursors (hSKP-HPC) were previously shown to be a promising in vitro tool for the evaluation of drug-induced hepatotoxicity. In this study, their capacity to identify potential liver-specific biomarkers at the gene expression level was investigated with particular emphasis on acute liver failure (ALF). To this end, a set of potential ALF-specific biomarkers was established using clinically relevant liver samples obtained from patients suffering from hepatitis B-associated ALF. Subsequently, this data was compared to data obtained from primary human hepatocyte cultures and hSKP-HPC, both exposed to the ALF-inducing reference compound acetaminophen. It was found that both in vitro systems revealed a set of molecules that was previously identified in the ALF liver samples. Yet, only a limited number of molecules was common between both in vitro systems and the ALF liver samples. Each of the in vitro systems could be used independently to identify potential toxicity biomarkers related to ALF. It seems therefore more appropriate to combine primary human hepatocyte cultures with complementary in vitro models to efficiently screen out potential hepatotoxic compounds.
    Toxicology in Vitro 10/2014; 29(6). DOI:10.1016/j.tiv.2014.10.012 · 3.21 Impact Factor
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    • "In 2006, Sokal's group performed a HTx for the correction of argininosuccinate lyase deficiency, and cell tracking confirmed their durable presence (12.5%) in the liver at 7 months after the last infusion [12]. More recent information on that same case confirmed that the patient was still doing well at up to 18 months when she received an OLT [13]. On the other hand, the majority of children undergoing HTx for urea cycle disorders have only been monitored for a relatively short time before OLT, though one 3-year-old patient with citrullinemia was still doing well 30 months after HTx [14]. "
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    Article: The Liver
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