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Potent Bystander
Effect in Suicide Gene Therapy Using Neural Stem Cells Transduced with
Herpes Simplex Virus Thymidine Kinase Gene
Shaoyi Li, Tsutomu Tokuyama, Junkoh
Yamamoto, Masayo Koide, Naoki Yokota, Hiroki Namba
Department of Neurosurgery, Hamamatsu University School of
Medicine, Hamamatsu, Japan -- Corresponding Author: Hiroki Namba, MD,
Department of Neurosurgery, Hamamatsu University School of Medicine,
1-20-1 Handayama, Hamamatsu, 431-3192 (Japan), Tel. +81 53 435 2281,
Fax +81 53 435 2282, E-Mail hnamba@hama-med.ac.jp -- Received: June
21, 2005; Accepted after revision: October 15, 2005; Published online:
January 16, 2006
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Objective. The herpes
simplex virus thymidine kinase (HSVtk)/ganciclovir suicide gene
therapy system has been considered as one of the most promising
therapeutic strategies for malignant gliomas.
We have been using HSVtk gene-transduced neural stem cells (NSCtk)
that possess an ability to migrate toward a tumor mass for the
treatment of experimental brain tumors.
In the present study, we evaluated the potency of anti-tumor effect
mediated by the bystander effect between NSCtk and C6 glioma cells in
the HSVtk/ganciclovir suicide gene therapy system.
Methods. NSCtk and C6
glioma cells were mixed at various ratios (NSCtk:C6 cell ratios of 1:1
to 1:64) and the bystander effect was evaluated both under in vitro
and in vivo conditions.
Results. In vitro
co-culture experiment showed a complete tumor growth inhibition at the
NSCtk:C6 ratios as low as 1:16.
In vivo co-implantation study in the rat brain showed no visible
tumors at the NSCtk:C6 ratios as low as 1:16 and all those rats
survived more than 100 days.
Conclusion. The results
clearly demonstrated an extremely potent bystander effect between
NSCtk and C6 cells, and the minimum number of NSCtk cells needed for
the treatment of tumors was roughly estimated.
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