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 language | English |
|---|---|
| Pages (from-to) | 572-578 |
| Number of pages | 7 |
| Journal | Cancer Gene Therapy |
| Volume | 19 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2012 |
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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 journal › Article
}
TY - JOUR
T1 - Therapeutic effect of suicide gene-transferred mesenchymal stem cells in a rat model of glioma
AU - Kosaka, H.
AU - Ichikawa, T.
AU - Kurozumi, Kazuhiko
AU - Kambara, H.
AU - Inoue, S.
AU - Maruo, T.
AU - Nakamura, K.
AU - Hamada, H.
AU - Date, Isao
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - bystander effect
KW - glioma
KW - mesenchymal stem cell
KW - suicide gene
UR - http://www.scopus.com/inward/record.url?scp=84864143971&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864143971&partnerID=8YFLogxK
U2 - 10.1038/cgt.2012.35
DO - 10.1038/cgt.2012.35
M3 - Article
C2 - 22744211
AN - SCOPUS:84864143971
VL - 19
SP - 572
EP - 578
JO - Cancer Gene Therapy
JF - Cancer Gene Therapy
SN - 0929-1903
IS - 8
ER -