Use of genetically engineered bone marrow-derived mesenchymal stem cells for glioma gene therapy.
In our previous study, we successfully treated an established C6 brain tumor using neural stem cells transduced with the herpes simplex virus-thymidine kinase gene (HSVtk) and ganciclovir in the rat. In the present study, we investigated the use of mesenchymal stem cells (MSCs), obtained from adult rats and transduced with HSVtk (MSCtk cells), instead of neural stem cells because MSCs are much easier to obtain from the adult subjects. Those cells were used for in vitro co-culture study and in vivo co-implantation study with C6 rat glioma cells to examine bystander tumoricidal effect, which revealed a sufficient bystander effect and only 1/32 MSCtk cells were needed for complete tumor eradication. In vitro bystander effect was also observed in a real-time fashion using a culture microscope and it was shown that only tumor cells that had contact with MSCtk cells died. In vivo treatment study of an established C6 brain tumor with an intratumoral injection of MSCtk cells followed by systemic ganciclovir administration demonstrated a significant reduction of the tumor size and a significant survival prolongation. The treatment strategy using MSCtk and ganciclovir (MSCtk therapy) is more feasible and practical for clinical application than the method using neural stem cells.
Amano
Shinji
S
Department of Neurosurgery, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu 431-3192, Japan.
Li
Shaoyi
S
Gu
Chunyu
C
Gao
Yun
Y
Koizumi
Shinichiro
S
Yamamoto
Seiji
S
Terakawa
Susumu
S
Namba
Hiroki
H
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001854:Bone Marrow Cells; D001932:Brain Neoplasms / Q000628:therapy*; D024201:Bystander Effect / Q000502:physiology; D015774:Ganciclovir / Q000627:therapeutic use*; D041722:Genes, Transgenic, Suicide; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus; D013937:Thymidine Kinase / Q000235:genetics
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir