title: Glioma tropism of lentivirally transduced hematopoietic progenitor cells.
abstract: Experimental gliomas attract hematopoietic progenitor cells (HPC) in vivo. HPC are therefore promising candidates for a cell-based delivery of therapeutic molecules to experimental gliomas. A therapeutic application requires efficient genetic manipulation of the cellular vector and a lack of tumorigenicity. Here, we studied the impact of lenti-viral transduction on the glioma tropism of human or murine HPC. Transduction of human or murine HPC with a GFP lentivirus (lenti-GFP) did not interfere with the glioma-mediated attraction of HPC. Bone marrow reconstitution of C57Bl/6 mice with syngeneic GFP-transgenic lineage-depleted bone marrow cells (lin- BM) was as efficient as reconstitution with syngeneic lin- BM transduced ex vivo with lenti-GFP. SMA-560 gliomas growing orthotopically in lenti-GFP-reconstituted VM/Dk mice recruited GFP-positive bone marrow-derived cells. Thus, lentiviral transduction did not interfere with the attraction of exogenously injected HPC or endogenous bone marrow-derived cells by experimental gliomas. Lenti-GFP-HPC implanted directly into tumor-free brains were not tumorigenic. The intravenous injection of lenti-GFP-HPC in glioma-bearing mice did not alter the survival of otherwise untreated animals and had no impact on the survival benefit conferred by cerebral irradiation. Taken together, genetic manipulation of HPC with lenti-GFP neither made these cells tumorigenic nor interfered with their glioma tropism.
authors.affiliation: Laboratory of Molecular Neurooncology, Department of General Neurology and Hertie Institute for Clinical Brain Research, University of Tubingen, Tubingen, Germany. ghazaleh.tabatabai@usz.ch
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Tabatabai
authors.forename: Kathy
authors.initials: K
authors.lastname: Hasenbach
authors.forename: Caroline
authors.initials: C
authors.lastname: Herrmann
authors.forename: Gabriele
authors.initials: G
authors.lastname: Maurer
authors.forename: Robert
authors.initials: R
authors.lastname: Möhle
authors.forename: Patrizia
authors.initials: P
authors.lastname: Marini
authors.forename: Manuel
authors.initials: M
authors.lastname: Grez
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000628:therapy*; D002465:Cell Movement / Q000502:physiology; D002469:Cell Separation; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000009:adverse effects / Q000502:physiology*; D005910:Glioma / Q000628:therapy*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology; D006801:Humans; D016086:Lentivirus; D051379:Mice; D008810:Mice, Inbred C57BL; D014161:Transduction, Genetic; D023041:Xenograft Model Antitumor Assays
chemical_list: D049452:Green Fluorescent Proteins