Basic fibroblast growth factor increases retroviral-mediated gene transfer into human hematopoietic peripheral blood progenitor cells.
Retroviral vector-mediated gene transfer into human hematopoietic stem cells (HSC) may permit gene therapy of certain genetic diseases. Stimulation of HSC with hematopoietic growth factors (GF) has been shown to increase the level of retroviral transduction. We have studied the effect of basic fibroblast growth factor (bFGF), alone and in combination with other GFs, on the efficiency of transfer of the bacterial neomycin phosphotransferase (neoR) gene into human CD34(+)-enriched peripheral blood hematopoietic progenitor cells. The combination of bFGF, interleukin-3 (IL-3), IL-6, and stem cell factor (SCF) resulted in a transduction efficiency of 37 and 35% for G418-resistant colony-forming units-granulocyte/macrophage (CFU-GM) and mixed colonies multipotent colony-forming units (CFU-GEMM), respectively, which was significantly higher than the corresponding figures obtained with IL-3, IL-6, and SCF. The optimal concentration of bFGF was between 20 and 200 ng/mL. bFGF alone had no effect on the transduction rate. These results indicated a synergism in the action of bFGF, IL-3, IL-6, and SCF to enhance gene transduction rates into human hematopoietic progenitor cells.
Dilber
M S
MS
Department of Medicine, Karolinska Institute, Huddinge Hospital, Sweden.
Björkstrand
B
B
Li
K J
KJ
Smith
C I
CI
Xanthopoulos
K G
KG
Gahrton
G
G
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D004347:Drug Interactions; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D006098:Granulocytes / Q000378:metabolism; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D019868:Kanamycin Kinase; D008264:Macrophages / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D012190:Retroviridae / Q000235:genetics*; D019089:Stem Cell Factor
D015703:Antigens, CD; D018952:Antigens, CD34; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D015850:Interleukin-6; D019089:Stem Cell Factor; D016222:Fibroblast Growth Factor 2; D017853:Phosphotransferases (Alcohol Group Acceptor); D019868:Kanamycin Kinase