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

Karen E. Pollok, Johannes C.M. Van der Loo, Ryan J. Cooper, Jennifer R. Hartwell, Kathryn R. Miles, Robert Breese, Emily P. Williams, Angela Montel, Roopa Seshadri, Helmut Hanenberg, David A. Williams

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The gene transfer efficiency into nonobese diabetic/severe combined immunodeficient (NOD/SCID)-repopulating cells (SRCs) derived from umbilical cord blood (UCB) (n = 11 NOD/SCID mice) and granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood (MPB) (n = 64 NOD/SCID mice) was compared using a clinically relevant protocol and a retrovirus vector expressing the enhanced green fluorescent protein (EGFP). At 6-9 weeks after transplantation, 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 the BM (2.2% ± 1.8%) and SPL (2.0% ± 2.6%) in recipients of MPB. In subsequent studies, MPB was cultured for 2-8 days in cytokines prior to transduction to determine if longer prestimulation was required for optimal gene transfer. A significant increase in gene transfer into CD45+ human cells and clonogenic cells derived from MPB SRCs was observed when cells were prestimulated for 6 days compared to 2 days prior to transduction (p = 0.019). However, even after 6 days of prestimulation, transduction was still significantly less than UCB. A substantial discrepancy exists in the ability to introduce genes effectively via retrovirus vectors into SRCs derived from MPB as compared to UCB.

Original languageEnglish (US)
Pages (from-to)2095-2108
Number of pages14
JournalHuman gene therapy
Volume12
Issue number17
DOIs
StatePublished - Nov 20 2001

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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