UCSDが「有線ミニチュア脳」作成プロトコルを世界で初めて開発(UC San Diego Develops First-In-Kind Protocol for Creating ‘Wired Miniature Brains’)

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2024-06-10 カリフォルニア大学サンディエゴ校(UCSD)

カリフォルニア大学サンディエゴ校の研究者が開発した新しい手法により、非常にリアルな脳皮質オルガノイド(小型人工脳)が作成可能になりました。この手法は、発達障害や統合失調症などの神経疾患研究に役立ちます。新技術は、患者の幹細胞から生成した神経ネットワークを研究でき、異なる脳領域が自然に共発展するため、複雑な脳回路の研究が進むと期待されています。これにより、治療薬や遺伝子治療のテストも可能になります。現在、アマゾン先住民のアルツハイマー病治療法の研究や、宇宙での実験が進行中です。

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複雑な神経振動を持つ「半誘導」皮質オルガノイドの生成 Generation of ‘semi-guided’ cortical organoids with complex neural oscillations

Michael Q. Fitzgerald,Tiffany Chu,Francesca Puppo,Rebeca Blanch,Miguel Chillón,Shankar Subramaniam & Alysson R. Muotri
Nature Protocols  Published:03 May 2024
DOI:https://doi.org/10.1038/s41596-024-00994-0

UCSDが「有線ミニチュア脳」作成プロトコルを世界で初めて開発(UC San Diego Develops First-In-Kind Protocol for Creating ‘Wired Miniature Brains’)

Abstract

Temporal development of neural electrophysiology follows genetic programming, similar to cellular maturation and organization during development. The emergent properties of this electrophysiological development, namely neural oscillations, can be used to characterize brain development. Recently, we utilized the innate programming encoded in the human genome to generate functionally mature cortical organoids. In brief, stem cells are suspended in culture via continuous shaking and naturally aggregate into embryoid bodies before being exposed to media formulations for neural induction, differentiation and maturation. The specific culture format, media composition and duration of exposure to these media distinguish organoid protocols and determine whether a protocol is guided or unguided toward specific neural fate. The ‘semi-guided’ protocol presented here has shorter induction and differentiation steps with less-specific patterning molecules than most guided protocols but maintains the use of neurotrophic factors such as brain-derived growth factor and neurotrophin-3, unlike unguided approaches. This approach yields the cell type diversity of unguided approaches while maintaining reproducibility for disease modeling. Importantly, we characterized the electrophysiology of these organoids and found that they recapitulate the maturation of neural oscillations observed in the developing human brain, a feature not shown with other approaches. This protocol represents the potential first steps toward bridging molecular and cellular biology to human cognition, and it has already been used to discover underlying features of human brain development, evolution and neurological conditions. Experienced cell culture technicians can expect the protocol to take 1 month, with extended maturation, electrophysiology recording, and adeno-associated virus transduction procedure options.

生物工学一般
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