title: Therapeutic effect of suicide gene-transferred mesenchymal stem cells in a rat model of glioma.
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.
authors: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan.
authors: H
authors: H
authors: Kosaka
authors: T
authors: T
authors: Ichikawa
authors: K
authors: K
authors: Kurozumi
authors: H
authors: H
authors: Kambara
authors: S
authors: S
authors: Inoue
authors: T
authors: T
authors: Maruo
authors: K
authors: K
authors: Nakamura
authors: H
authors: H
authors: Hamada
authors: I
authors: I
authors: Date
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism; D005437:Flucytosine / Q000008:administration & dosage; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy; D005910:Glioma / Q000235:genetics / Q000628:therapy*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000628:therapy; D051381:Rats
chemical_list: D005437:Flucytosine; D043525:Cytosine Deaminase