Induction of midbrain-like organoids from human pluripotent stem cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21306
• Project/Area Number (Other): 18H06202 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Nara Medical University
• Principal Investigator: NANAURA HITOKI 奈良県立医科大学, 医学部附属病院, 研究員 (00827909)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 脳オルガノイド / 神経細胞 / ドパミン / 中脳 / パーキンソン病

Outline of Final Research Achievements

Brain organoids derived from human pluripotent stem cells recapitulate the course of human brain development, and they seem to be useful for medical research on central nervous system disorders such as Parkinson disease. There are few reports of brain organoids mimicking the structure of midbrain. In this study, we aim to develop a new method to induce midbrain-like organoids.
Brain organoids were generated at one month, and immunohistochemistry and quantitative polymerase chain reaction confirmed the gene expression of dopaminergic neurons, such as thyrosin hydroxylase. RNA-seq analysis also revealed that the brain organoids contained cell populations like that of a human brainstem. Therefore, our brain organoids might be a useful model of the brainstem.

Free Research Field

脳神経内科学

Academic Significance and Societal Importance of the Research Achievements

これまでのヒト脳オルガノイド樹立プロトコルは、大脳皮質構造の再現を目的とするものが多く、中脳など脳幹部の構造を再現可能な手法は限られていた。本研究により、中脳を含めた脳幹部を模倣した脳オルガノイドを短期間で作製する手法を確立した。今後本手法は、パーキンソン病を含めた中枢神経疾患の病因解明や、治療薬剤のスクリーニングなどに有用なモデルとなると考えられる。