| Project/Area Number |
21H03046
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 56010:Neurosurgery-related
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| Research Institution | Keio University |
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Principal Investigator |
toda masahiro 慶應義塾大学, 医学部(信濃町), 教授 (20217508)
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| Co-Investigator(Kenkyū-buntansha) |
植田 良 慶應義塾大学, 医学部(信濃町), 講師 (30317143)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2023: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2022: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2021: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | Glioma / iPS / Neural stem cell / Viral vector / Suicide gene / Genome editing / 悪性神経膠腫 / 神経幹細胞 / 自殺遺伝子 / 透明化 / iPS細胞 / 複製型レトロウイルス / グリオーマ / Malignant glioma / 遊走 / NSC / RRV / suicide gene / 遺伝子治療 |
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| Outline of Research at the Start |
悪性神経膠腫（グリオーマ）は、グリオーマ幹細胞（GSC）の存在により、強い浸潤性お
よび治療抵抗性を示す。本研究では、治療抵抗性・浸潤性GCSに追従するiPS細胞由来神経
幹細胞を、自殺遺伝子搭載複製型ウイルスの”producing cell” かつ“delivery vehicle”として用いる革新的な新規治療法を開発する。
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| Outline of Final Research Achievements |
Glioblastoma is characterized by diffuse infiltration into the normal brain. Invasive glioma stem cells (GSCs) are an underlying cause of treatment failure. New therapeutic approach targeting invasive GSCs is required. In this study, we showed that human iPS cell-derived neural stem cells (NSCs) could efficiently produce viral vector. Optimal culture condition of viral vector -producing NSCs was found. Infection rate was quantitatively evaluated in vitro. Furthermore, three-dimensional images of brain clearing revealed that NSCs trafficked to the GSCs and produced viral vector covered the broad area of invasive GSCs. Finally, our established NSCs showed antitumor effects in GSC mouse models, leading to the prolonged survival. Our results indicate the potential benefit of viral vector-producing NSCs for invasive GSCs. Furthermore, the present research concept may become a platform to promote clinical studies using human iPS cell.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により樹立される治療用NSCは、グリオーマの浸潤性を克服する新たな治療戦略となり、グリオーマの生命予後の改善につながる可能性がある。またグリオーマで治療成績を残すことが出来た際には、その他の膵癌をはじめとする悪性・難治性腫瘍にも応用可能であり汎用性も高く社会的意義も大きい。この研究開発はiPS細胞を再生医療以外の疾患(がん)治療に応用する極めて革新的な1st clinical trial となり得るプロジェクトと言える。
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