Gene-cell therapy using iPS cells for the treatment of brain tumor

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15648
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Keio University
• Principal Investigator: TODA MASAHIRO 慶應義塾大学, 医学部(信濃町), 准教授 (20217508)
• Co-Investigator(Renkei-kenkyūsha): MINE Yutaka 慶應義塾大学, 医学部, 訪問研究員 (10306730)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 脳腫瘍学 / ゲノム編集 / 幹細胞 / 自殺遺伝子

Outline of Final Research Achievements

In this study, the HSV-tK gene was firstly transduced into neural stem cells (NSCs) differentiated from human iPS cells using a viral vector. HSV-tk expressing iPS-NSCs were transplanted into human brain tumor model mice, and the effectiveness of this therapy by administration of ganciclovir (GCV) was demonstrated. Next, HSV-tk gene was introduced into iPS by genome editing, but HSV-tk expressing iPS cell line could not be established due to cytotoxicity. Then, Tet-inducible HSV-tk transduced iPS cells were established using gene expression induction system. After induction of differentiation into therapeutic NSCs, these NSCs were transplanted into brain tumor model mice. After administration of GCV with Doxycycline, a remarkable therapeutic effect of this therapy using gene expression induction system was confirmed.

Free Research Field

脳神経外科学