Genetically-engineered multilineage-differentiating stress-enduring cells as cellular vehicles against malignant gliomas

2016 Fiscal Year Final Research Report

• Project/Area Number: 25293306
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Namba Hiroki 浜松医科大学, 医学部, 教授 (60198405)
• Co-Investigator(Kenkyū-buntansha): 天野 慎士 浜松医科大学, 医学部, 特任研究員 (70464138) ; 徳山 勤 浜松医科大学, 医学部附属病院, 講師 (90313957)
• Co-Investigator(Renkei-kenkyūsha): DEZAWA MARI 東北大学, 医学部, 教授 (50272323)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: glioma / gene therapy / stem cells / bystander effect / migration / viral thymidine kinase / ganciclovir

Outline of Final Research Achievements

Suicide gene therapy based on the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) is an efficient strategy for treating malignant gliomas. In the present study, we evaluated treatment with multilineage-differentiating stress-enduring (Muse) cells, endogenous non- tumorigenic pluripotent-like stem cells, as carriers of the HSVtk gene. HSVtk gene-transduced human Muse cells (Muse-tk cells) showed a potent in vivo bystander effect and migratory activity toward glioma cells. Intracranial U87 gliomas in nude mouse brains injected intratumorally with Muse-tk cells followed by intraperitoneal GCV administration were significantly reduced in size within 2 weeks. These findings suggest that intratumoral Muse-tk cell injection followed by systemic GCV administration is safe and effective, and that allogeneic Muse-tk cell-medicated suicide gene therapy for malignant glioma is clinically feasible.

Free Research Field

脳神経外科学