Repopulation of adult and neonatal mice with human hepatocytes: A chimeric animal model

Research output: Contribution to journalArticle

Abstract

We report the successful transplantation of human hepatocytes in immunodeficient, fumarylacetoacetate hydrolase-deficient (fah-/-) mice. Engraftment occurs over the entire liver acinus upon transplantation. A few weeks after transplantation, increasing concentrations of human proteins (e.g., human albumin and human C3a) can be measured in the blood of the recipient mouse. No fusion between mouse and human hepatocytes can be detected. Three months after transplantation, up to 20% of the mouse liver is repopulated by human hepatocytes, and sustained expression of lentiviral vector transduced gene can be observed. We further report the development of a hepatocyte transplantation method involving a transcutaneous, intrahepatic injection in neonatal mice. Human hepatocytes engraft over the entire injected lobe with an expansion pattern similar to those observed with intrasplenic transplantation.

Details

Authors
Organisations
External organisations
  • Salk Institute for Biological Studies
Research areas and keywords

Keywords

  • Fumarylacetoacetate hydrolase, Hepatocyte transplantation, IL-2 receptor common gamma chain, Lentivirus, Recombination activating gene 2
Original languageEnglish
Pages (from-to)20507-20511
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number51
Publication statusPublished - 2007 Dec 18
Publication categoryResearch
Peer-reviewedYes