| Project/Area Number |
17K10516
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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 |
General surgery
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| Research Institution | Nagasaki University |
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Principal Investigator |
TAKATSUKI Mitsuhisa 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (80380939)
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| Co-Investigator(Kenkyū-buntansha) |
池田 裕明 長崎大学, 医歯薬学総合研究科(医学系), 教授 (40374673)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 細胞シート / 組織適合性抗原 / 肝細胞 / 細胞性拒絶 / 肝移植 / 拒絶回避 / ゲノム編集 / MHC分子 / 移植・再生医療 |
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| Outline of Final Research Achievements |
We used the CRISPR/Cas9 system to develop a cell sheet in which major histocompatibility antigen (MHC). The CRISPR/Cas9 system was introduced into a liver cancer cell line, and then treatment-cells cultured on a temperature-responsive culture dish for 7 days to prepare a cell sheet. The treatment-hepatocyte sheet was subcutaneously transplanted into a wild mouse to evaluate cellular rejection. As a result of H&E staining of the subcutaneous section, the immune system cells were scattered around the cell sheet and immune rejection was not occurred. Therefore, it was suggested that MHC-knock out hepatocyte by CRISPR / Cas9 system hardly cause cellular rejection and these cells is a possibility to promise cell source in allogeneic transplantation.
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| Academic Significance and Societal Importance of the Research Achievements |
臓器あるいは細胞の他家移植時に生じる細胞性拒絶は主要組織適合抗原 (major histocom-patibility complex：MHC)によって制御されている。細胞性拒絶の制御においては移植後の免疫抑制剤によって行われているものの、過剰な免疫抑制は感染や悪性腫瘍、薬剤性腎障害等の副作用を引き起こしてしまう。このような問題点を解決させる方法としてドナー細胞表面に存在するMCHに着目し、CRISPR/Cas9システムを用いてMCH抑制細胞の開発ならびに移植後の細胞性拒絶反応に関して検討することで新たな移植細胞源の確保が期待できる。
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