SDF-1α/CXCL 12 enhances retroviral-mediated gene transfer into immature subsets of human and murine hematopietic progenitor cells

W. Tao, G. Hangoc, S. Cooper, H. E. Broxmeyer

Research output: Contribution to journalReview article

6 Scopus citations

Abstract

Genetic modification of hematopoietic stem and progenitor cells has the potential to treat diseases affecting blood cells. Oncoretroviral vectors have been used for gene therapy; however, clinical success has been limited in part by low gene transfer efficiencies. We found that the presence of stromal-derived factor 1 (SDF-1α)/CXCL12 during retroviral transduction significantly enhanced, in a dose-dependent fashion, gene transfer into immature subsets of high proliferative human and murine hematopoietic progenitor cells. Murine mononuclear bone marrow cells and purified c-Kit+ Lin- bone marrow cells were prestimulated and transduced with the bicistronic retroviral vector MIEG3 on Retronectin-coated surfaces in the presence and absence of SDF-1. SDF-1 enhanced gene transduction of murine bone marrow and c-Kit+ Lin- cells by 35 and 29%, respectively. Moreover, SDF-1 enhanced transduction of progenitors in these populations by 121 and 107%, respectively. SDF-1 also enhanced transduction of human immature subsets of high proliferative progenitors present in either nonadherent mononuclear or CD34+ umbilical cord blood cells. Transduction of hematopoietic progenitors was further increased by preloading Retronectin-coated plates with retrovirus using low-speed centrifugation followed by increasing cell-virus interactions through brief centrifugation during the transduction procedure. These results may be of clinical relevance.

Original languageEnglish (US)
Pages (from-to)61-69
Number of pages9
JournalGene Therapy
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2004

Keywords

  • Gene transfer
  • Hematopoietic stem and progenitor cells
  • Oncoretroviral vectors
  • SDF-1

ASJC Scopus subject areas

  • Genetics

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