Human hepatocyte transplantation: state of the art.

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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Most current drug screening assays used to identify new drug candidates are 2D cell-based systems, even though such in vitro assays do not adequately re-create the in vivo complexity of 3D tissues. Inadequate representation of the human tissue environment during a preclinical test can result in inaccurate predictions of compound effects on overall tissue functionality. Screening for compound efficacy by focusing on a single pathway or protein target, coupled with difficulties in maintaining long-term 2D monolayers, can serve to exacerbate these issues when using such simplistic model systems for physiological drug screening applications. Numerous studies have shown that cell responses to drugs in 3D culture are improved from those in 2D, with respect to modeling in vivo tissue functionality, which highlights the advantages of using 3D-based models for preclinical drug screens. In this review, we discuss the development of microengineered 3D tissue models that accurately mimic the physiological properties of native tissue samples and highlight the advantages of using such 3D microtissue models over conventional cell-based assays for future drug screening applications. We also discuss biomimetic 3D environments, based on engineered tissues as potential preclinical models for the development of more predictive drug screening assays for specific disease models.
    Journal of the Association for Laboratory Automation 11/2014; · 1.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Improving cell viability and function are important for enhancing the clinical results of cell transplantation. The relationship between cell viability and shear stress remains unexplained, and sedimentation effects during the infusion process are important to the hepatocyte transplantation process. In the present study, the relationship between cell viability and shear stress in the presence of sedimentation effect was investigated using a microchannel simulating the cell transplantation process under several shear stress conditions. Horizontal and vertical syringe orientations were employed to investigate the sedimentation effect. The vertical syringe orientation resulted in lower viability loss than the horizontal orientation. In summary, removing a sedimentation effect is important to improving cell viability by preventing high shear stress.
    Cell Medicine. 02/2015; 7(2):59-66.
  • [Show abstract] [Hide abstract]
    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; · 3.21 Impact Factor


1 Download