| Project/Area Number |
16K10377
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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 |
Radiation science
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| Research Institution | National Institutes for Quantum and Radiological Science and Technology |
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Principal Investigator |
Takizawa Kazuya 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線障害治療研究部, 研究員(任非) (20739388)
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| Project Period (FY) |
2016-04-01 – 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 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 間葉系幹細胞 / 造血幹細胞 / 放射線障害 / ヒト化マウス / iPS細胞 |
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| Outline of Final Research Achievements |
In this study, we tried to evaluate the protective effects of human mesenchymal stem cells (MSCs) on radiation-induced damage of tissue stem cells, by using humanized mouse model. We tried to generate the humanized mouse model by co-transplantion of human hematopoietic stem cells (HSCs) with human MSCs or transplantation of the human HSCs alone into bone marrow of a hyper immunodeficiency NOG mouse. However, contrary to my expectation, the human HSCs was not detected in peripheral blood of the transplanted mouse at from 4 to 6 months after the transplantation, indicating difficulty of reconstitution of intramedullary hematopoietic microenvironments. In addition, in order to generate MSCs with higher radioprotective effects, MSCs were induced from human iPS cells. The exosomes derived from the induced MSCs (iMSCs) improved the survival rate of irradiated- HSCs in vitro.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により開発された評価系は、ヒト由来の細胞やタンパク質などとの相互作用がよりヒト生体内での反応を反映したものとなると考えられ、これまでの放射線照射マウス実験系よりも一歩踏み込んだ知見を得られるツールとして、放射線障害治療に向けた創薬基盤などに活用されることが期待できる。
一方で、iPS細胞より作製されたiMSCを解析する事により、これまで多くの報告がなされてきたMSCの多様な組織障害治癒効果をもたらしている生物活性の中心的な作用機序を明らかにすると供に、遺伝子改変等によって目的の組織障害に合せた機能的なMSCを作出する医療的応用への足がかりとなる。
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