Ontogeny-recapitulating generation of human pluripotent stem cell-derived cerebellar organoids

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03812
• 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: Kansai Medical University
• Principal Investigator: MUGURUMA Keiko 関西医科大学, 医学部, 教授 (30209978)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: オルガノイド / 小脳 / 自己組織化 / プルキンエ細胞 / 多能性幹細胞 / 三次元培養 / タイムラプスイメージング / 神経分化

Outline of Final Research Achievements

Brain organoids are self-organised 3D structures of pluripotent stem cells, and are widely used in academic research on development and evolution as brain tissue models that mimic early neural development, and in applied research such as regenerative medicine and pathological research. While a series of elementary processes seen in development can be reproduced in cerebral organoids, the formation and maturation of tissue structures are still insufficient in cerebellar organoids, and the previously reported culture techniques can only reproduce tissue construction equivalent to the late embryonic stage in human. The aim of this project was to create a more advanced cerebellar organoid model by combining the induction and promotion of the self-assembly capacity of pluripotent stem cells with cell assembly, and to contribute to a novel model for human cerebellar research.

Free Research Field

神経発生学、幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

脳オルガノイドはiPS細胞など多能性幹細胞が自己組織的に三次元構造を形成した細胞の塊であり、ヒト脳の研究や再生医療・創薬研究のin vitroヒト脳モデルとして有用である。小脳は発生過程が複雑で、ヒト小脳の形成には未解明な部分が多く、あらたなヒト小脳モデルの開発が求められている。また、脊髄小脳変性症や多系統萎縮症など小脳の神経細胞が特異的に変性する疾患も多く、病態解明・創薬・治療法開発のためにもヒト小脳を再現したオルガノイドの分化誘導法の開発は極めて重要であり、本研究はこれら課題に寄与するものである。