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 |
English
|
Copyright Holders | © Nature Publishing Group
|
File Version | author
|
Refereed |
True
|
DOI | |
Web of Science KeyUT |