Document Detail

Migratory neural stem cells for improved thymidine kinase-based gene therapy of malignant gliomas.
MedLine Citation:
PMID:  15670759     Owner:  NLM     Status:  MEDLINE    
Gene therapy of glioma based on viral delivery of herpes simplex virus type I thymidine kinase (HSV-TK) has failed in the clinic because of low transduction efficacy. To circumvent this problem, this study evaluated highly migratory HSV-TK-transduced neural stem cells (NSC) for their ability to kill untransduced glioma cells by a gap junction-mediated bystander effect. The admixture of HSV-TK-transduced NSC to U87MG and LN-18 human malignant glioma cell lines at ratios of 1:10 or 1:1 eliminated more than 50% or 90% of glioma cells in the presence of ganciclovir (25 microM). Glioma cell cytotoxicity required cell-cell contact. Similarly, tumor cell cytotoxicity was observed in two of three primary glioblastoma cell cultures, and the presence of this bystander effect correlated with the expression of connexin 43 in the untransduced glioma target cells. In conclusion, we delineate a role for migratory HSV-transfected NSC to eliminate glioma cells purely by means of the bystander effect.
Martin Uhl; Markus Weiler; Wolfgang Wick; Andreas H Jacobs; Michael Weller; Ulrich Herrlinger
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  328     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-01-26     Completed Date:  2005-03-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  125-9     Citation Subset:  IM    
Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany.
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MeSH Terms
Bystander Effect / physiology*
Cell Line, Tumor
Cell Movement / physiology
Gap Junctions / physiology
Gene Therapy / methods*
Glioma / drug therapy*
Neurons / enzymology*,  secretion*,  transplantation
Stem Cell Transplantation / methods*
Thymidine Kinase / genetics,  secretion,  therapeutic use*
Treatment Outcome
Viral Proteins / genetics,  secretion,  therapeutic use*
Reg. No./Substance:
0/Viral Proteins; EC 2.7.1.-/thymidine kinase, Canid herpesvirus 1; EC Kinase

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