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

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

Research output: Contribution to journalArticle

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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
Pages (from-to)2095-2108
Number of pages14
JournalHuman Gene Therapy
Volume12
Issue number17
DOIs
StatePublished - 2001

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Granulocyte Colony-Stimulating Factor
Fetal Blood
SCID Mice
Retroviridae
Genes
Spleen
Bone Marrow Cells
Blood Cells
Transplantation
Bone Marrow
Cytokines

ASJC Scopus subject areas

  • Genetics

Cite this

Differential transduction efficiency of SCID-repopulating cells derived from umbilical cord blood and granulocyte colony-stimulating factor-mobilized peripheral blood. / Pollok, Karen; Hanenberg, Helmut; Williams, David A.; Van der Loo, Johannes C M; Cooper, Ryan J.; Hartwell, Jennifer R.; Miles, Kathryn R.; Breese, Robert; Williams, Emily P.; Montel, Angela; Seshadri, Roopa.

In: Human Gene Therapy, Vol. 12, No. 17, 2001, p. 2095-2108.

Research output: Contribution to journalArticle

Pollok, K, Hanenberg, H, Williams, DA, Van der Loo, JCM, Cooper, RJ, Hartwell, JR, Miles, KR, Breese, R, Williams, EP, Montel, A & Seshadri, R 2001, 'Differential transduction efficiency of SCID-repopulating cells derived from umbilical cord blood and granulocyte colony-stimulating factor-mobilized peripheral blood', Human Gene Therapy, vol. 12, no. 17, pp. 2095-2108. https://doi.org/10.1089/10430340152677430
Pollok, Karen ; Hanenberg, Helmut ; Williams, David A. ; Van der Loo, Johannes C M ; Cooper, Ryan J. ; Hartwell, Jennifer R. ; Miles, Kathryn R. ; Breese, Robert ; Williams, Emily P. ; Montel, Angela ; Seshadri, Roopa. / Differential transduction efficiency of SCID-repopulating cells derived from umbilical cord blood and granulocyte colony-stimulating factor-mobilized peripheral blood. In: Human Gene Therapy. 2001 ; Vol. 12, No. 17. pp. 2095-2108.
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AU - Cooper, Ryan J.

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