Cell therapy for liver disease.

ABSTRACT

The clinical demand for whole organ transplantation for the treatment of end-stage liver disease far outstrips supply. As a result, research efforts have focused on hepatocyte therapies to support this scarce clinical resource, including the investigation of alternative cell sources, in particular bone marrow cells (BMCs). In animal models of metabolic liver disease, adopting strategies that provide a selective advantage for transplanted hepatocytes have proved to be highly effective in repopulating recipient livers, and the current relatively poor success rate of hepatocyte transplants in humans can be attributed to the lack of a clinically applicable procedure to induce a similar repopulation of the human liver. Autologous BMCs have been transplanted in a number of clinical trials involving patients with liver cirrhosis; modest improvements in liver health have been reported, but the mechanisms responsible for these effects are currently unknown. Transplanted hepatocytes can effectively repopulate a metabolically deficient liver, provided that a selective advantage exists for the donor cells. Some reports suggest that BMCs can differentiate into hepatocytes, but for the treatment of cirrhosis, the primary goal is to render the ingressing cells capable of degrading the excessive collagen associated with the disease. This review presents the progress and discusses some of the problems that need to be overcome in the field of cell transplantation for the treatment of metabolic and fibrogenic liver diseases.