Hepatocyte transplantation in a model of toxin-induced liver disease: variable therapeutic effect during replacement of damaged parenchyma by donor cells

Nat Med. 2000 Mar;6(3):320-6. doi: 10.1038/73179.

Abstract

To provide long-term therapy in patients with severe toxin-induced hepatic parenchymal damage, donor hepatocytes would need to replicate and replace a large portion of the damaged parenchyma. Using a mouse model developed to reproduce this type of hepatic injury, we found that hepatocyte transplantation only slightly improved survival after transplantation despite the fact that many non-survivors showed moderate liver repopulation by donor cells. Perhaps accounting for this outcome, donor parenchyma in non-survivors did not have typical lobular organization. These results indicate that the re-creation of functional parenchyma by transplanted hepatocytes requires time, during which donor cells proliferate and then establish normal parenchymal architecture.

Publication types

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

MeSH terms

  • Alkaline Phosphatase / genetics
  • Animals
  • Cell Transplantation*
  • Disease-Free Survival
  • Enhancer Elements, Genetic
  • Ganciclovir / toxicity*
  • Genetic Therapy
  • Herpesvirus 1, Human / enzymology
  • Herpesvirus 1, Human / genetics
  • Humans
  • Liver / cytology*
  • Liver / drug effects
  • Liver / pathology
  • Liver Neoplasms, Experimental / chemically induced
  • Liver Neoplasms, Experimental / pathology*
  • Liver Neoplasms, Experimental / therapy*
  • Metallothionein / genetics
  • Mice
  • Mice, Transgenic
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins / biosynthesis
  • Serum Albumin / genetics
  • Thymidine Kinase / genetics

Substances

  • Recombinant Fusion Proteins
  • Serum Albumin
  • Metallothionein
  • Thymidine Kinase
  • Alkaline Phosphatase
  • Ganciclovir