Liver transplantation is the accepted method of treatment for end stage liver disease. The improvements in patient and graft survival have mainly resulted from the developments in immunosuppressive drug therapy. Advances in surgical techniques, now allow the use of auxiliary liver transplantation in the management of patients with acute liver failure and certain liver based metabolic defects such as Crigler-Najjar syndrome, urea cycle defects, and familial hypercholesterolaemia.  The success of auxiliary transplantation in humans has supported the observation in animal experiments that relatively small amounts of liver tissue can correct the underlying metabolic defect. This has led to the interest in using human hepatocytes for cell transplantation in the management of various liver-based metabolic conditions and acute liver failure.

There are a number of potential advantages of hepatocyte transplantation if the technique can prove successful. It avoids the risks and undertaking of major surgery and as the native liver is still in place can help bridge a patient to whole organ transplant or allow liver regeneration in the case of acute liver failure. There is the possibility of better utilisation of donor organs which remain in short supply, particularly if methods can be developed to isolate good quality hepatocytes from marginal donor livers, currently rejected for clinical transplantation. Hepatocyte transplantation has been used as a new treatment for acute liver failure and metabolic liver diseases such as Crigler-Najjar syndrome type I , glycogen storage disease type 1a , and urea cycle defects  for long-term correction of the underlying metabolic deficiency.

Considerable progress has been made in bringing hepatocyte transplantation to the bedside. However, there are a number of areas for improvement and development. In terms of the livers currently available to isolate hepatocytes, fatty livers are those most commonly rejected for clinical transplantation and represent an important potential source for hepatocytes. Thus improvement of the outcome of isolation and purification of cells from fatty livers is key part of future research plans.

There is no doubt that stem cells offer the potential to overcome the current limitations of both supply of hepatocytes and the extent of repopulation of the liver after transplantation. Human foetal hepatocytes, presumably with greater numbers of stem cells, were administered intraperitoneally to patients with fulminant hepatic failure in 1994. Our group has since used alginate micro encapsulated human hepatocytes in the management of acute liver failure in new born babies with  success in avoiding transplantation or as bridge to transplantation.

Sources of stem cells for therapy could be foetal hepatocytes, cord blood , embryonic, and bone marrow. This is the focus of research world-wide on stem cell biology and there is no doubt that there are many hurdles to cross before any clinical application. If these are overcome then stem cells could differentiate into all types of liver cells, be easier to cryopreserve and thaw with good function, have proliferative capacity in vitro and in vivo, may be less immunogenic and could  be used for in vitro gene therapy. Autotransplantation of stem cells would avoid the need of immunosuppression and its attendant problems and this could be combined with specific gene replacement eg. ornithine transcarbamylase, bilirubin glucuronyltransferase.

In summary the experience gained so far in the handling of hepatocytes and hepatocyte transplantation gives a good basis for the application of the stem cell technologies now being developed