Liver repopulation with hepatocyte transplantation: new avenues for gene and cell therapy

J Gene Med. 1999 Nov-Dec;1(6):386-92. doi: 10.1002/(SICI)1521-2254(199911/12)1:6<386::AID-JGM73>3.0.CO;2-Z.

Abstract

Liver-directed gene therapy is appropriate for many conditions. Recent work established that liver repopulation with transplanted cells can be effective in treating genetic disorders. Although hepatocytes express therapeutic genes with considerable efficiency, correction of genetic disorders is constrained by limitations in permanent gene transfer into hepatocytes and repopulation of the liver with transplanted cells. Adenoviral vectors are highly efficient for hepatic gene transfer but the onset of deleterious host immune responses against adenoviral vectors, along with clearance of transduced hepatocytes have caused problems. Nonetheless, recent work concerning engraftment and proliferation of transplanted hepatocytes in the liver has provided significant new information, which should refocus interest in hepatocyte-based therapies. Moreover, hepatocyte transplantation systems offer creative tools for defining critical mechanisms in gene regulation and survival of transduced cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Animals, Congenic
  • Cell Survival
  • Cell Transplantation*
  • Cells, Cultured / transplantation
  • Genetic Diseases, Inborn / genetics
  • Genetic Diseases, Inborn / therapy
  • Genetic Therapy / methods*
  • Humans
  • Liver / cytology*
  • Mice
  • Mice, Mutant Strains
  • Rabbits
  • Rats
  • Rats, Inbred F344
  • Recombinant Fusion Proteins / physiology
  • Transfection

Substances

  • Recombinant Fusion Proteins