Potent bystander effect in suicide gene therapy using neural stem cells transduced with herpes simplex virus thymidine kinase gene

Oncology. 2005;69(6):503-8. doi: 10.1159/000091032. Epub 2006 Jan 16.


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.

MeSH terms

  • Animals
  • Antiviral Agents / administration & dosage
  • Bystander Effect*
  • Coculture Techniques
  • Ganciclovir / administration & dosage
  • Gene Transfer Techniques*
  • Genes, Transgenic, Suicide*
  • Genetic Therapy / methods*
  • Neurons*
  • Rats
  • Rats, Sprague-Dawley
  • Simplexvirus*
  • Stem Cells*
  • Thymidine Kinase / genetics*


  • Antiviral Agents
  • Thymidine Kinase
  • Ganciclovir