| Project/Area Number |
16K19494
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Kidney internal medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Research Collaborator |
Nishinakamura Ryuichi
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 腎臓 / ネフロン前駆細胞 / 糸球体 / 尿細管 / SIX2 / iPS / オルガノイド / ネフロン / 再生医療 / hiPS / 発生・分化 / 再生医学 / 細胞・組織 |
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| Outline of Final Research Achievements |
During development, nephron progenitor forming one million nephrons, a functional unit in the kidney. Nephron consists of glomeruli and renal tubules play a critical role to maintain homeostasis. However, nephron progenitor ceases after birth in mice, and before birth in human when they terminally differentiated to the nephron. Thus, no new nephron formed in adult kidney, which may explain the irreversible nature of diseased kidney. Our lab established the method for induction of nephron progenitors from human iPS cells. In order to propagate the human nephron progenitors, we generated iPS cell lines that express GFP in the SIX2 locus by TALEN and then purified SIX2-positive population from iPS-derived tissues by FACS. Isolated SIX2-positive cells were propagated and maintained robust capacity for nephron formation both in vitro and in vivo. The expanded cells also maintained their nephron-forming potential after freezing. Thus, our methods will be useful for regenerative medicine.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトの腎臓再生には大量の細胞数の確保が必要である。糸球体と尿細管の3次元構造を形成する分化能を維持したネフロン前駆細胞を大幅に増幅させる培養法を確立できれば、この問題を解決することができる。さらに凍結保存が可能になれば、ネフロン前駆細胞をヒトiPS細胞から約２週間かけて増幅する時間を大幅に短縮し、腎臓再生や発生の研究者への提供が可能となる。これらは、ネフロン前駆細胞からポドサイトの大量調整等により、透析に代わる治療法の開発や、患者由来iPSによる疾患モデル研究の創出など、腎臓再生医療の基盤となることが期待される。
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