Hepatocyte Transplantation: Development of New Systems for Liver Repopulation and Gene Therapy

Abstract

Following recent advances in molecular and cell biology, development of hepatocyte transplantation has been considerably invigorated. To study the fate of hepatocytes transplanted into the liver, new strategies have included the use of endogenously marked transgenic hepatocytes. Release of peripherally quantifiable marker proteins by transgenic hepatocytes has provided noninvasive ways to determine hepatocyte engraftment and prolonged survival. Further characterization of intrasplenic hepatocyte transplantation has established this to be the most suitable method for targeting hepatocytes to the liver. Advances in gene cloning, retrovirology, and gene transfer technology have provided further tools for accomplishing gene therapy. Practical strategies for ex vivo gene therapy involving hepatocytes have been developed by exploiting these new technologies. The potential value of hepatocyte transplantation in acute hepatic failure has begun to be reexamined. Therefore, hepatocyte transplantation can be predicted to provide new ammunition for continuing our assault on untreatable disorders. Resolution of outstanding issues should accelerate this process.