| Project/Area Number |
18K08225
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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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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Nihon University |
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Principal Investigator |
OIKAWA Osamu 日本大学, 医学部, 研究医員 (60813590)
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| Co-Investigator(Kenkyū-buntansha) |
福田 昇 日本大学, 総合科学研究所, 教授 (40267050)
阿部 雅紀 日本大学, 医学部, 教授 (70459890)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 遺伝性多発性嚢胞腎 / 疾患特異的iPS細胞 / 個別医療 / 多発性嚢胞腎 / エピゲノム / 臨床試験 |
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| Outline of Final Research Achievements |
In order to select effective medicines to suppress the cyst-formations in patients with autosomal dominant polycystic kidney disease (ADPKD), we established kidney organoids from the disease-specific iPS cells derived from peripheral mononuclear blood cells. We confirmed structure of collecting duct in the kidney organoids by immunostaining of E-cadhelin, aquaporin 2, vasopressin 2 receptor. We could completely eliminate the contamination of undiffareciated iPS cells in kidney organoids with rBC2LCN-PE23.The kidney organoids showed excessive enlargement responses of collecting duct in the kidney organoids from patients with ADPKD compaired to kidney organoid from normal healthy paerson in responses to vasopressin and folskorin. We will investigate effective medicines including pioglitazone, tacrolims, somatostatin, metoformine and torvaptane supressing the excessive enlargement of the patients-derived kidney organoids.
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| Academic Significance and Societal Importance of the Research Achievements |
ADPKDは遺伝性腎臓疾患であり、遺伝子変異heterogenityがある。今回ADPKD患者疾患特異的iPS細胞から腎臓オルガノイドを確立しバソプレシン、フォルスコリンに対する集合管増大反応にも遺伝子変異の違いから集合管上皮の増殖に違いを認めた。今後オルガノイドの増大抑制にトルバプタム、ピオグリタゾン、ソマトスタチン、タクロリムス、ラパマイシンの中で最も有効な薬剤の評価を行い、遺伝子変異heterogenity を基にADPKDの個別医療の確立につなげていければ、医療社会的意義も大きい。
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