Therapeutic effect of suicide gene-transferred mesenchymal stem cells in a rat model of glioma

Cancer Gene Ther. 2012 Aug;19(8):572-8. doi: 10.1038/cgt.2012.35. Epub 2012 Jun 29.


We evaluated a new therapeutic strategy for malignant glioma, which combines intratumoral inoculation of mesenchymal stem cells (MSCs) expressing cytosine deaminase gene with 5-fluorocytosine (5-FC) administration. For in vitro and in vivo experiments, MSCs were transfected with adenovirus carrying either enhanced green fluorescent protein gene (AdexCAEGFP) or cytosine deaminase gene (AdexCACD), to establish MSC-expressing EGFP (MSC-EGFP) or CD (MSC-CD). Co-culture of 9L glioma cells with MSC-CD in a medium containing 5-FC resulted in a remarkable reduction in 9L cell viability. The migratory ability of MSC-EGFP toward 9L cells was demonstrated by double-chamber assay. For the in vivo study, rats harboring 9L brain tumors were inoculated with MSC-EGFP or MSC-CD. Immunohistochemistry of rat brain tumors inoculated with MSC-EGFP showed intratumoral distribution of MSC-EGFP. Survival analysis of rats bearing 9L gliomas treated with intratumoral MSC-CD and intraperitoneal 5-FC resulted in significant prolongation of survival compared with control animals. In conclusion, molecular therapy combining suicide gene therapy and MSCs as a targeting vehicle represents a potential new therapeutic approach for malignant glioma, both with respect to the antitumor potential of this system and its neuroprotective effect on normal brain tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / therapy*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coculture Techniques
  • Cytosine Deaminase* / genetics
  • Cytosine Deaminase* / metabolism
  • Flucytosine / administration & dosage
  • Genes, Transgenic, Suicide / genetics*
  • Genetic Therapy
  • Glioma / genetics
  • Glioma / therapy*
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Neoplasms, Experimental / therapy
  • Rats


  • Flucytosine
  • Cytosine Deaminase