Liver organoid derived from iPSCs transplant to Cynomolgus monkey with liver cirrhosis
Project/Area Number |
18KK0252
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Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
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Research Institution | The University of Tokyo (2019-2020) Yokohama City University (2018) |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
村田 聡一郎 横浜市立大学, 医学部, 准教授 (40436275)
鄭 允文 横浜市立大学, 医学研究科, 客員准教授 (80404995)
聶 運中 横浜市立大学, 医学研究科, 客員研究員 (00831330)
久世 祥己 東京大学, 医科学研究所, 特任研究員 (70837806)
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Project Period (FY) |
2018-10-09 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2019: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
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Keywords | ips細胞 / カニクイザル / 肝硬変 / iPS細胞 |
Outline of Final Research Achievements |
We aimed to explore the allogeneic transplantation of iPS cells derived liver organoid in cynomolgus monkeys with liver fibrosis. First of all, we reprogrammed monkey peripheral blood mononuclear cells into iPS cells using the auto-erasable Sendai virus vector and identified the cellular characteristics of monkey iPS cells in vitro. Based on the experience on human iPS differentiation, we have optimized the protocols and differentiated monkey iPS cells into hepatic endoderm, endothelial progenitor cells and mesenchymal progenitor cells. By co-culturing these three progenitor cells in a three-dimensional microwell culture plate, we successfully generated monkey iPS cells derived liver organoid. After 8 weeks of subcutaneousl injection of Thioacetamide, we generated novel method of monkey liver fibrosis model.
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Academic Significance and Societal Importance of the Research Achievements |
肝硬変は様々な原因で発症する慢性肝疾患の終末像であり、肝移植以外に根治療法がない。肝硬変患者は国内に数十万存在し、毎年肝不全等で1万7000人程度が亡くなっているが、圧倒的な肝移植ドナー不足の状態である。カニクイザルは肝臓の構造がヒトに類似しているため前臨床試験の有用性が極めて高いが、安定的な入手が困難である。中国の中山大学ではカニクイザルを数万頭飼育する施設が存在し、国際共同研究によってサルを有効活用できる大きなメリットがある。
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Report
(4 results)
Research Products
(12 results)