2018 Fiscal Year Final Research Report
Rat liver disease modeling with humanized liver and immune system
| Project/Area Number |
16K15604
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Digestive surgery
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Zheng Yunwen 筑波大学, 医学医療系, 准教授 (80404995)
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| Co-Investigator(Kenkyū-buntansha) |
田村 孝史 筑波大学, 医学医療系, 研究員 (20633192)
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| Research Collaborator |
OHKOUCHI Nobuhiro
FURUYA Kinji
GE Jianyun
FURUTA Tomoaki
SAKO Daisuke
IWASAKI Kinichi
LIU Liping
SHIMIZU Yoshio
LIANG Chen
SONG Dan
UCHIDA Yoshiaki
RAMIREZ R. Sabrina
YAGI Hiroya
HAMADA Hiromi
ISODA Hiroko
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | ヒト化ラット / 再生医療 / 羊膜上皮細胞 / 肝オルガノイド / 血管内皮前駆細、 / 造血幹細胞 / 間葉系細胞 |
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| Outline of Final Research Achievements |
The amnion stem cells from the placenta have been reported to have not only the pluripotent characteristics similar to ES cells, but also the liver differentiation potential. Here we evaluated the characteristics of the amnion stem cells and confirmed the new features, that the hepatic related gene expression increased when incubated on the special 3D cultural system. Furthermore, we tried to generate humanized liver and immune system in severe immunodeficient rat. Human hepatic repopulating in rat model was established, however, since the macrophage, human cord blood cells could not existed in the model longer. Only macrophage removed thoroughly, the limit reconstitution of human hematopoietic stem cells could be confirmed. Xenograft rejection with the transplantation of hematopoietic stem cells markedly elevated, by this model, explore the mechanism of rejection from macrophage and reconstitute human immune system in humanized liver become possible.
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| Free Research Field |
幹細胞生物学と再生医学
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| Academic Significance and Societal Importance of the Research Achievements |
肝硬変・肝不全による死者は国内で年間2万人を超えるが、唯一の根治的治療である肝移植は深刻な臓器不足に直面しており、世界的な問題となっている。臓器移植の代替治療として、幹細胞を用いた新規治療法の開発は重要な課題である。重症免疫不全ラットに対してヒト臍帯血由来造血幹細胞や体性細胞を移植することにより、正常な機能を有する肝組織を再構築することが可能となり、創薬研究などに役立つヒト肝臓動物モデルの作成や肝不全に対抗する新たな移植治療の実現が期待される。さらに、造血幹細胞移植は異種拒絶が顕著にでる移植モデルであり、マクロファージの拒絶メカニズム解明は、ヒト化肝臓ラットにも応用が可能と考えられる。
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