title: Bystander effect in glioma suicide gene therapy using bone marrow stromal cells.
abstract: An established rat intracranial glioma was successfully treated through the tumoricidal bystander effect generated by intratumoral injection of rat bone marrow stromal cells (BMSCs) transduced with the herpes simplex virus-thymidine kinase gene (BMSCtk cells) followed by systemic ganciclovir administration. In the present study, we tested the bystander effect of this treatment strategy when using human BMSCs as the vector cells. Human BMSCtk cells were mixed with various kinds of brain tumor cell lines (human and rat glioma cells) and examined in vitro and in vivo tumoricidal bystander effects, by co-culture study and co-implantation study in the nude mouse, respectively. A significant in vitro bystander effect was observed between human BMSCtk cells and any of the tumor cells examined in the ganciclovir-containing medium. A potent in vivo bystander effect against human and rat glioma cells was also demonstrated when ganciclovir was administered. Migratory activity of the human BMSCs toward the tumor cells was enhanced by the conditioned media obtained from both human and rat glioma cells compared to the fresh media. The results of this study have demonstrated that the bystander effect generated by BMSCtk cells and ganciclovir is not cell type-specific, suggesting that the strategy would be quite feasible for clinical use.
authors.affiliation: Department of Neurosurgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Shaoyi
authors.initials: S
authors.lastname: Li
authors.forename: Chunyu
authors.initials: C
authors.lastname: Gu
authors.forename: Yun
authors.initials: Y
authors.lastname: Gao
authors.forename: Shinji
authors.initials: S
authors.lastname: Amano
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Koizumi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tokuyama
authors.forename: Hiroki
authors.initials: H
authors.lastname: Namba
mesh_terms: D000818:Animals; D024201:Bystander Effect; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology; D013045:Species Specificity; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D055815:Young Adult
chemical_list: D013937:Thymidine Kinase; D015774:Ganciclovir