Hepatocyte cell therapy in liver disease

Abstract

Liver disease is a leading cause of morbidity and mortality. Liver transplantation remains the only proven treatment for end-stage liver failure but is limited by the availability of donor organs. Hepatocyte cell therapy, either with bioartificial liver devices or hepatocyte transplantation, may help address this by delaying or preventing liver transplantation. Early clinical studies have shown promising results, however in most cases, the benefit has been short lived and so further research into these therapies is required. Alternative sources of hepatocytes, including stem cell-derived hepatocytes, are being investigated as the isolation of primary human hepatocytes is limited by the same shortage of donor organs. This review summarises the current clinical experience of hepatocyte cell therapy together with an overview of possible alternative sources of hepatocytes. Current and future areas for research that might lead towards the realisation of the full potential of hepatocyte cell therapy are discussed.

Keywords:

• acute liver failure
• bioartificial liver device
• cell therapy
• hepatocyte cell therapy
• hepatocyte transplantation
• inborn errors of metabolism
• liver failure

Financial & competing interests disclosure

DC Bartlett has received funding from an Medical Research Council Clinical Research Training Fellowship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• The incidence of liver disease is increasing.

• Liver transplantation remains the only proven treatment for end-stage liver failure but the demand for donor organs is greater than the supply.

• Hepatocyte cell therapy may be one way to address the shortage of donor organs but is limited by a reliable supply of hepatocytes.

• A number of alternative sources of hepatocytes, including induced pluripotent stem cell cells, have been investigated and could offer a potential limitless source of hepatocyte-like cells. The optimal cell type, differentiation, storage and method of delivery must be ascertained.

• Bioartificial liver devices could potentially offer a temporary treatment while the liver recovers or as a bridge to orthotopic liver transplantation but there is little current evidence of long-term benefit.

• Hepatocyte transplantation has the potential to be a definitive treatment but long-term efficacy has yet to be demonstrated.

• Techniques to improve and monitor the engraftment, survival and function of transplanted hepatocytes are needed to optimise outcomes.

• Continued research and larger clinical trials are required to aid the translation of hepatocyte cell therapy into routine clinical practice.