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

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

Research output: Contribution to journalArticle

37 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

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Therapeutic Uses
Mesenchymal Stromal Cells
Glioma
Suicide
Genes
Flucytosine
Cytosine Deaminase
Brain Neoplasms
Aptitude
Neuroprotective Agents
Survival Analysis
Coculture Techniques
Adenoviridae
Genetic Therapy
Cell Survival
Therapeutics
Immunohistochemistry

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology

Cite this

Therapeutic effect of suicide gene-transferred mesenchymal stem cells in a rat model of glioma. / Kosaka, H.; Ichikawa, T.; Kurozumi, Kazuhiko; Kambara, H.; Inoue, S.; Maruo, T.; Nakamura, K.; Hamada, H.; Date, Isao.

In: Cancer Gene Therapy, Vol. 19, No. 8, 08.2012, p. 572-578.

Research output: Contribution to journalArticle

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, vol. 19, no. 8, pp. 572-578. https://doi.org/10.1038/cgt.2012.35
Kosaka, H. ; Ichikawa, T. ; Kurozumi, Kazuhiko ; Kambara, H. ; Inoue, S. ; Maruo, T. ; Nakamura, K. ; Hamada, H. ; Date, Isao. / Therapeutic effect of suicide gene-transferred mesenchymal stem cells in a rat model of glioma. In: Cancer Gene Therapy. 2012 ; Vol. 19, No. 8. pp. 572-578.
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