| Project/Area Number |
15H01803
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
松本 司 いわき明星大学, 薬学部, 教授 (00173906)
岳 鳳鳴 信州大学, 学術研究院医学系, 助教 (20532865)
田中 榮司 信州大学, 学術研究院医学系, 教授 (50163506)
友常 大八郎 信州大学, 学術研究院医学系, 助教 (80283802)
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| Research Collaborator |
Hirashima Kanji
Yokoyama Tadayuki
Takizawa Sakiko (Shirasawa Sakiko)
Matsushima Yoshito
Sakai Tomomi
Isono Kunio
Okada Kazuyuki
Seki Azusa
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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 |
¥38,870,000 (Direct Cost: ¥29,900,000、Indirect Cost: ¥8,970,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2017: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2016: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2015: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
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| Keywords | 再生医工学 / 網羅的遺伝子解析 / 細胞移植 / 分化肝細胞 |
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| Outline of Final Research Achievements |
This project has aimed at a creation of accessory hepatic tissues or organ in the subcutaneous of the small intestine using pluripotent stem cells instead of liver transplantation. Stem cell-derived differentiated cells established by ammonia environment demonstrated that undifferentiated state was almost lost completely, expressed genes featured with hepatocytes, absorbed ICG definitely, and disclosed up-regulation of ornitin associated with urea cycle and G-1-P & G-6-P with glycometabolis by metabolome inclusive analysis. Obtained hepatocytes from pluripotent stem cells were transplanted into the subcutaneous tissue of the small intestine of nude rats and rhesus monkeys, and survived there. Thus, this research has succeeded in continuity from the basic research to translational one.
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| Academic Significance and Societal Importance of the Research Achievements |
このプロジェクトでは、多能性幹細胞は、過酷な環境に自らを変貌させ、それに適応する形で生まれ変わることを証明した。このことは、今後の分化誘導法の開発のみならず細胞生物学的な視点からも学術的に大きな意義がある。
次に、臓器移植に伴う倫理的問題を払拭する意味でも、移植を代替する治療法が長く望まれてきた。このプロジェクトでは、多能性幹細胞由来肝細胞を腸管粘膜下に移植し、腸管を肝臓化することで新たな副次肝を作り出し、この期待に応えようとしたものである。かつこの研究をトランスレイショナルリサーチまで持ち込むことができたのは、将来の現実化に向け、社会的意義が高いと考える。
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