Decreased homing of retrovirally transduced human bone marrow CD34 + cells in the NOD/SCID mouse model

Kristin M. Hall, Tamara L. Horvath, Rafat Abonour, Kenneth Cornetta, Edward F. Srour

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Objective. Many clinical gene therapy trials have described poor engraftment of retrovirally transduced CD34+ cells. Because engraftment is dependent upon successful homing of graft cells to the bone marrow (BM), we examined whether retroviral-mediated gene transfer (RMGT) induces a homing defect in CD34+ cells. Methods. Homing of fluorescently labeled human BM CD34+ cells transduced with three separate retroviral vectors (MFG-eGFP, LNC-eGFP, and LXSN) was assessed in nonobese diabetic/severe combined immunodeficient mice. Results. Homing of transduced CD34+ cells was significantly decreased 20 hours after transplantation compared with freshly isolated control and cultured untransduced control cells. Specifically, homing of GFP+ cells in the graft was preferentially decreased thus skewing the contribution of transduced cells to engraftment. Transduced cells were not selectively trapped in other organs and BM-homed transduced cells did not undergo apoptosis at a higher rate than untransduced cells. Adhesion molecule expression and binding activity was not altered by RMGT. This homing defect was reversed when transduced cells were cultured over CH-296 for 2 additional days with SCF only. Conclusion. These data suggest that RMGT of hematopoietic cells may compromise their homing potential and implicate transduction-induced reduced homing in the observed low engraftment of retrovirally transduced CD34+ cells. These results may have a direct clinical application in gene therapy protocols.

Original languageEnglish (US)
Pages (from-to)433-442
Number of pages10
JournalExperimental Hematology
Volume34
Issue number4
DOIs
StatePublished - Apr 1 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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