Differential transduction efficiency of SCID-repopulating cells derived from umbilical cord blood and granulocyte colony-stimulating factor-mobilizedperipheral blood

The gene transfer efficiency into nonobese diabetic/severe combined immunod eficient (NOD/SCID)-repopulating cells (SRCs) derived from umbilical cord b lood (UCB) (n = 11 NOD/SCID mice) and granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood (MPB) (n = 64 NOD/SCID mice) was compar ed using a clinically relevant protocol and a retrovirus vector expressing the enhanced green fluorescent protein (EGFP). At 6-9 weeks after transplan tation, the frequency of transduced human cells in the bone marrow (BM) (40 .5% +/- 2.4% [mean +/- SE]) and spleen (SPL) (36.4% +/- 3.2%) in recipients of UCB cells was significantly higher (p < 0.001) than that observed in th e BM (2.2% +/- 1.8%) and SPL (2.0% +/- 2.6%) in recipients of MPB. In subse quent studies, MPB was cultured for 2-8 days in cytokines prior to transduc tion to determine if longer prestimulation was required for optimal gene tr ansfer. A significant increase in gene transfer into CD45(+) human cells an d clonogenic cells derived from MPB SRCs was observed when cells were prest imulated for 6 days compared to 2 days prior to transduction (p = 0.019). H owever, even after 6 days of prestimulation, transduction was still signifi cantly less than UCB. A substantial discrepancy exists in the ability to in troduce genes effectively via retrovirus vectors into SRCs derived from MPB as compared to UCB.