| Project/Area Number |
15K09601
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
樋口 孝 東京慈恵会医科大学, 医学部, 助教 (30595327)
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| Research Collaborator |
Ohashi Toya
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | iPS細胞 / ＭＰＳ / クラッベ病 / 神経系スフェア / 治療補助用デバイス / 神経細胞デバイス / 神経系起源基細胞 / 遺伝子改変 / ムコ多糖症 / 治療用デバイス / ジンクフィンガー / デバイス / 自家移植 / 遺伝子編集 / iPS細胞を分化させて |
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| Outline of Final Research Achievements |
Mucopolysaccharidosis (MPS) and Krabbe's disease are diseases in which substrates are accumulated and damaged by enzyme deficiency. In this study, we used the disease-derived iPS cells to differentiate into organ lineages, evaluated the therapeutic effect of gene modification systems such as viral vectors, and aimed to realize autologous therapeutic therapeutic devices. MPS type VII, Krabbe's iPS cells have been successfully created and maintained. At first, we try to induce differentiation of neural cells from iPS cells derived from Krabbe's disease model mouse, and successfully induce differentiation into nervous system spheres. However, the induction of differentiation into neural lineage-derived base cells and individual lineage neurons was not sufficiently successful, and we have not succeeded to shift to comparative experiments with and without gene transfer using lentiviral vectors.
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| Academic Significance and Societal Importance of the Research Achievements |
ライソゾーム病は細胞内小器官であるライソゾーム関連酵素の欠損により基質が蓄積し、臓
器不全を呈する疾患群の総称である。このうちMPS は酵素欠損により中枢神経、肝、脾、心、腎、骨系統などにGAG が蓄積し、多発性臓器障害を来すとされる。現在Ⅰ型、Ⅱ型、VI 型において酵素補充療法が保険承認されているが、中枢神経系、心弁膜症・心筋症、骨系統合併症には効果が不十分とされている。またクラッベ病も酵素欠損により中枢神経系が主に障害され、現在有効な保険承認治療がない。これらの疾患の予後向上を目指し、重要臓器の病態解析および治療戦略としてのデバイス作成を計画した。
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