Follistatin allows efficient retroviral-mediated gene transfer into rat liver.
Retroviral vectors are widely used tools for gene therapy. However, in vivo gene transfer is only effective in dividing cells, which, in liver, requires a regenerative stimulus. Follistatin is effective in promoting liver regeneration after 90% and 70% hepatectomy in rats. We studied its efficacy on liver regeneration and retroviral-mediated gene delivery in 50% hepatectomized rats. When human recombinant follistatin was infused into the portal vein immediately after 50% hepatectomy, hepatocyte proliferation was significantly higher than in control 50% hepatectomized rats. A single injection of virus particles administered 23 h after follistatin infusion resulted in more than 20% gene transduction efficiency in hepatocytes compared to 3% in control rats. It is concluded that a single injection of follistatin induces onset of proliferation in 50% hepatectomized rats and allows efficient retroviral-mediated gene transfer to the liver.
Borgnon
Josephine
J
INSERM EMI 00-20 and University Paris XI, Bicêtre Hospital, Kremlin-Bicêtre, France.
Djamouri
Fatima
F
Lorand
Isabelle
I
Rico
Virginie Di
VD
Loux
Nathalie
N
Pages
Jean-Christophe
JC
Franco
Dominique
D
Capron
Frédérique
F
Weber
Anne
A
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D038681:Follistatin / Q000008:administration & dosage*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D008115:Liver Regeneration / Q000187:drug effects* / Q000235:genetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012190:Retroviridae / Q000235:genetics*; D014162:Transfection / Q000379:methods*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D038681:Follistatin; D001616:beta-Galactosidase