Self-organizing urinary tract from human pluripotent stem cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03801
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Takasato Minoru 国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (40788676)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ヒト多能性幹細胞 / 腎臓オルガノイド / 膀胱オルガノイド / 尿路系 / ウォルフ管 / 総排泄腔

Outline of Final Research Achievements

In this study, four types of tissue progenitor cells (nephron progenitor cells, Wolffian duct epithelium, bladder epithelium, and bladder surrounding cells) were generated from human pluripotent stem cells. By combining nephron progenitor cells with Wolffian duct epithelium, the early stages of kidney development were recapitulated. By combining bladder epithelial cells with bladder surrounding cells, bladder organoids were created. Finally, by combining Wolffian duct epithelium with bladder epithelium, we successfully recapitulated the extension of the Wolffian duct to the cloaca. These results indicate that the four types of tissue progenitor cells generated in this study exhibited sufficient self-organizing ability when combined with each other. In the future, similar methods will be used to advance the formation of an integrated urinary system in vitro.

Free Research Field

オルガノイド生物学

Academic Significance and Societal Importance of the Research Achievements

生体内で血液をろ過し、尿を生成・排出できる尿路系の構築は、機能の失われた腎臓を代替するという、腎臓再生医療の究極的目的そのものである。本研究成果はその実現に直接的に貢献する。人間は便宜的に三胚葉（内、中、外胚葉）を区別して扱っているが、生物は胚葉の垣根無しに組織をうまく組み合わせて機能系（例えば、肺と心臓と血管、門脈と肝臓と脾臓、骨と筋肉と神経など）を構築している。一つの生理機能（尿の生成と排出）を再現するために、複数の胚葉から構成される臓器（腎臓、尿管、膀胱）を自己組織化によりin vitroで構築する本研究は、胚葉の垣根を横断した生理機能系の一体構築という新規概念の先鞭となる。