ABSTRACT
Source of Hepatic Cells Ana Bonora-Centelles,1,a Ramiro Jover Atienza,2
Orthotopic liver transplantation (OLT) is currently the only available effective treatment for life-threatening liver diseases. However, this clinical practice is limited by the shortage of organ donors. In Europe, inherited metabolic diseases represent 26 percent of OLT-treated cases. However, the number of patients on waiting lists for liver transplantation who die (11 percent) has increased in recent years as a result of the severe shortage of organs, and this fi gure is as high as 80 percent in patients with fulminant hepatic failure. Hepatocyte transplantation may prove to be an alternative
1Unidad de Hepatología Experimental, Centro de Investigación, IIS-Hospital La Fe, Av. Campanar 21, 46009 Valencia, Spain. aEmail: abonora_cen@hotmail.com bEmail: jose.castell@uv.es cEmail: gomez_mjo@gva.es 2Departamento de Bioquímica y Biología Molecular, Universidad de Valencia, Av. Blasco Ibáñez 15, 46010 Valencia, Spain 3Centro de Transfusiones de la Comunidad Valenciana, Av. Del Cid 65, 46014 Valencia, Spain. Email: mirabet_vic@gva.es *Corresponding author
to whole-organ transplantation in acute liver failure for the correction of certain metabolic liver disorders and for late-stage liver diseases. One of the limitations of hepatocyte transplantation is the restricted availability of donor liver tissue. Application of hepatocytes for transplantation purposes demands high-quality cell preparations, which depend on the nature of the tissue used for cell harvesting to a large extent. Primary human hepatocytes are considered the gold standard model as they express the majority of hepatic functions and drug metabolizing enzymes, respond to enzyme inducers and are capable of generating in vitro a metabolic profi le similar to that found in vivo (Gómez-Lechón et al. 2004a, Hewitt et al. 2007). However, hepatocytes show phenotypic instability and have restricted accessibility. The main sources of tissue for hepatocyte isolation are segments from reduced cadaveric grafts and marginal livers that are unsuitable for transplantation, where steatosis is a major reason to discard liver grafts (Akhter et al. 2007, Dhawan et al. 2006). Not only tissue sources, but also hepatocyte isolation methods and preservation procedures, are key factors for cell transplantation. Different techniques using collagenase perfusion have been developed to obtain human hepatocytes from unused donor liver tissue (Alexandrova et al. 2005, Dhawan et al. 2006, Donato et al. 2005, Tanaka et al. 2006). However, initial liver damage or liver diseases, such as fi brosis or steatosis, may cause reduced metabolic functions of isolated cells. Although establishing banks of cryopreserved hepatocytes is feasible, with which some clinical success has been reported (Schneider et al. 2006, Stephenne et al. 2005), this may not solve the cell shortage problems because human hepatocytes are very sensitive to the freezingthawing procedure (Gómez-Lechón et al. 2006, Grondin et al. 2009). Hence, it is necessary to investigate new hepatic cell sources and strategies for clinical applications.
