Hepatocyte growth factor expressed by a retrovirus-producing cell line enhances retroviral transduction of primary hepatocytes: implications for in vivo gene transfer.
Hepatocyte Growth Factor (HGF) is the more potent mitogen of mature hepatocytes. We have examined the effect of human HGF expression by a recombinant retroviral cell line (MFG-LacZ) on retroviral transduction of primary mouse and human hepatocytes. The HGF in the supernatant of MFG-LacZ cell line was correctly processed and biologically active. Transduction of mouse and human hepatocytes with the supernatant of transfected cells was increased 5-fold, as determined by beta-galactosidase activity. The production of HGF was stable and did not interfere with the viral titers of the producer cells. This study provides evidence that expression of HGF within a retrovirus-producer cell line increases the transduction rate of primary hepatocytes. Since the number of corrected cells is a limiting step for phenotypic correction of liver deficiencies, our approach should improve hepatic gene therapy efficiency. Furthermore this cell line should be useful for in vivo liver gene therapy.
Pagès
J C
JC
INSERM U380, ICGM, Hôpital Cochin, Paris, France.
Loux
N
N
Bellusci
S
S
Farge
D
D
Bennoun
M
M
Vons
C
C
Jouanneau
J
J
Franco
D
D
Briand
P
P
Weber
A
A
D000818:Animals; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D008099:Liver; D051379:Mice; D011994:Recombinant Proteins; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic / Q000187:drug effects*
D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor