Liver transplantation is an important therapeutic option for many individuals with metabolic
liver disease. Nevertheless, the invasive nature of surgery and limitations of donor organ availability have led to the search for alternatives to whole-
organ transplantation. Cell-based
therapies have been a particularly active area of investigation in recent years. Hepatocyte
transplantations have been performed for a variety of indications, including
acute liver failure,
end-stage liver disease, and
inborn errors of metabolism. Individuals with
inborn errors of metabolism who have undergone hepatocyte
transplantation have shown clinical improvement and partial correction of the underlying metabolic defect. In most cases, sustained benefits have not been observed. This may be related to inadequate cell dose, variations in the quality of hepatocyte preparations, rejection of the transplanted cells, or senescence of transplanted hepatocytes. Though initial proof of concept with hepatocyte
transplantation has been demonstrated by a number of investigators, wide application of this technology has been hindered by the inability to secure a reliable and well-characterized cell source(s) for
transplantation and by the challenges of sustained engraftment and expansion of transplanted cells in vivo. Cell-based
therapies, including those based on stem cells or more differentiated progenitor cells, may represent the future of
cell transplantation for treatment of metabolic
liver disease.