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

H. Kosaka, T. Ichikawa, K. Kurozumi, H. Kambara, S. Inoue, T. Maruo, K. Nakamura, H. Hamada, I. Date

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42 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)572-578
Number of pages7
JournalCancer Gene Therapy
Volume19
Issue number8
DOIs
Publication statusPublished - Aug 2012

Keywords

  • bystander effect
  • glioma
  • mesenchymal stem cell
  • suicide gene

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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    Kosaka, H., Ichikawa, T., Kurozumi, K., Kambara, H., Inoue, S., Maruo, T., Nakamura, K., Hamada, H., & Date, I. (2012). Therapeutic effect of suicide gene-transferred mesenchymal stem cells in a rat model of glioma. Cancer Gene Therapy, 19(8), 572-578. https://doi.org/10.1038/cgt.2012.35