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Fas/CD95 pathway induces mouse liver regeneration and allows for highly efficient retrovirus‐mediated gene transfer
Author(s) -
Guidotti JacquesEmmanuel,
Mallet Vincent O.,
Parlier David,
Mitchell Claudia,
Fabre Monique,
Jaffray Patrick,
Lambert Martine,
Kahn Axel,
Gilgenkrantz Hélène
Publication year - 2001
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2001.20678
Subject(s) - transduction (biophysics) , hepatocyte , biology , microbiology and biotechnology , cytolysis , liver regeneration , fas receptor , in vivo , signal transduction , genetic enhancement , apoptosis , virology , gene , regeneration (biology) , in vitro , programmed cell death , genetics , cytotoxicity , biochemistry
Stable gene transfer into hepatocytes has been proposed to compensate for genetic deficiencies that affect liver function, or to deliver diffusible factors into the circulation. This strategy can be achieved using retroviral vectors; however, cell division must occur. We describe a simple and reproductive method that enables the induction of hepatocyte replication in a controlled fashion, thus allowing an efficient in vivo retroviral liver transduction that is applicable to mouse models of human genetic disorders. The approach is based on liver susceptibility to apoptosis via the Fas/CD95 pathway. We show that, 4 days following a single Fas agonist antibody (JO2) injection, hepatocyte replication occurs, the intensity of which is correlated with the level of the induced hepatic cytolysis. This treatment enables in vivo liver transduction, and its efficiency also correlates with the level of hepatic cytolysis. When recombinant retroviral vectors were infused intravenously during the period of hepatocyte replication, 15.4% ± 1.7% of the hepatocytes were transduced, reaching up to 32.5%.