Human Hepatocyte Transplantation: Three Decades of Clinical Experience and Future Perspective

Orthotopic liver transplantation (OLT) is the current standard of care for both chronic and acute terminal liver disease. However, a major limitation of this treatment is the shortage of healthy donor organs and the need for life-long immunosuppression to prevent graft rejection. Hepatocyte transplantation (HTx) has emerged as a promising, alternative therapeutic approach to either replace OLT or to act as a bridge until a donor liver becomes available thus reducing waiting list mortality. HTx involves the infusion and engraftment of human hepatocytes, typically isolated from organs unsuitable for OLT, into recipient liver parenchyma to carry out the missing hepatic function of the native cells. HTx is less invasive than OLT and can be performed repeatedly if required. The safety of clinical HTx has been shown and treatment results are promising, especially in patients with liver-based metabolic disorders. Nevertheless, HTx has failed to become the standard of care treatment for such disorders. This review aims to evaluate the progress that has been made within the field of HTx over the last 30 years and identify potential shortcomings within the approach which may be hindering its routine clinical application. Graphical Abstract