title: SDF-1alpha/CXCL12 enhances retroviral-mediated gene transfer into immature subsets of human and murine hematopoietic progenitor cells.
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-1alpha)/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.
authors.affiliation: Department of Microbiology and Immunology, The Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202-5181, USA.
authors.forename: W
authors.initials: W
authors.lastname: Tao
authors.forename: G
authors.initials: G
authors.lastname: Hangoc
authors.forename: S
authors.initials: S
authors.lastname: Cooper
authors.forename: H E
authors.initials: HE
authors.lastname: Broxmeyer
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D049452:Green Fluorescent Proteins; D006402:Hematologic Diseases / Q000628:therapy; D006412:Hematopoietic Stem Cells; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D012190:Retroviridae / Q000235:genetics*; D014161:Transduction, Genetic / Q000379:methods
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins