Glioma tropism of lentivirally transduced hematopoietic progenitor cells.
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.
Tabatabai
Ghazaleh
G
Laboratory of Molecular Neurooncology, Department of General Neurology and Hertie Institute for Clinical Brain Research, University of Tubingen, Tubingen, Germany. ghazaleh.tabatabai@usz.ch
Hasenbach
Kathy
K
Herrmann
Caroline
C
Maurer
Gabriele
G
Möhle
Robert
R
Marini
Patrizia
P
Grez
Manuel
M
Wick
Wolfgang
W
Weller
Michael
M
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
D049452:Green Fluorescent Proteins