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ID 49558
FullText URL
Author
Kosaka, H
Kambara, H
Inoue, S
Maruo, T
Nakamura, K
Hamada, H
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.
Keywords
glioma
mesenchymal stem cell
suicide gene
bystander effect
Published Date
2012-08
Publication Title
Cancer Gene Therapy
Volume
volume19
Issue
issue8
Publisher
Nature Publishing Group
Start Page
572
End Page
578
ISSN
0929-1903
NCID
AA12570566
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1038/cgt.2012.35
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/49136
language
英語
Copyright Holders
© Nature Publishing Group
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author
Refereed
True
DOI
Web of Science KeyUT