Kidney reconstitution and and disease modeling based on nephron induction methods in vitro

2021 Fiscal Year Final Research Report

• Project/Area Number: 17H06177
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Kumamoto University
• Principal Investigator: Nishinakamura Ryuichi 熊本大学, 発生医学研究所, 教授 (70291309)
• Project Period (FY): 2017-05-31 – 2022-03-31
• Keywords: 腎臓オルガノイド / ネフロン前駆細胞 / 尿管芽 / 間質前駆細胞 / iPS細胞 / ES細胞

Outline of Final Research Achievements

We induced kidney organoids via nephron progenitors from iPS cells derived from a patient with congenital nephrotic syndrome and recapitulated the initial disease states, including impaired formation of glomerular filtration slits. We also developed an induction method for the ureteric bud, the second renal progenitor, and applied it to autosomal dominant polycystic kidney disease to reproduce cyst formation. Furthermore, we successfully induced stromal progenitors and combined them with two other progenitors derived from mouse ES cells to reconstitute the higher-order kidney structures, all of which were derived from pluripotent stem cells.

Free Research Field

腎臓発生学

Academic Significance and Societal Importance of the Research Achievements

腎臓を構成する３種の前駆細胞を多能性幹細胞から誘導する方法を、３つとも世界に先駆けて開発した。それらを組み合わせて、全て多能性幹細胞由来のマウス腎臓の高次構造を作製できたことは、将来の移植医療に大きく貢献する。ヒトiPS細胞から同様の腎臓構造作製が待たれる。またヒトiPS細胞からの誘導法を用いて２つの腎疾患の病態再現に成功したことは、疾患の病因解明と創薬に繋がることが期待される。