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. Stim ulation of HSC with hematopoietic growth factors (GF) has been shown t o increase the level of retroviral transduction. We have studied the e ffect of basic fibroblast growth factor (bFGF), alone and in combinati on with other GFs, on the efficiency of transfer of the bacterial neom ycin phosphotransferase (neoR) gene into human CD34(+)-enriched periph eral blood hematopoietic progenitor cells. The combination of bFGF, in terleukin-3 (IL-3), IL-6, and stem cell factor (SCF) resulted in a tra nsduction efficiency of 37 and 35% for G418-resistant colony-forming u nits-granulocyte/macrophage (CFU-GM) and mixed colonies multipotent co lony-forming units (CFU-GEMM), respectively, which was significantly h igher 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 gen e transduction rates into human hematopoietic progenitor cells.