yrammuS 要概組織再生を促す技術は，試験管内で3次元的に作られた臓器オルガノイドの創成や，再生医療に貢献する．再現性の高いオルガノイド形成や，生体親和性の高い材料を用いた組織再生は未だ困難であり，その達成には技術革新が必要不可欠である．組織発生は，繊維状の細胞外マトリクスが細胞の足場として働き，細胞遊走と細胞分化を誘導し進行する．この生体内機序に倣い，本研究では，脳オルガノイドや神経組織再生を可能とし，高い生体親和性を有するペプチドを基盤とする人工細胞外マトリクスの開発を行った．均一性の高い線維を形成し，細胞接着性を有する独自ペプチドを基盤に，成長因子徐放性を組み込むことで生体内で血管新生を誘導し，単回投与で損傷脳回復を可能にする初めての材料の開発に成功した．Technologies that promote tissue regeneration will contribute to the creation of organoids made three-dimen-sionally in vitro and to regenerative medicine. Tissue regeneration using highly reproducible organoid formation and biocompatible materials remains difficult, and technological innovation is essential to achieve this goal. Tissue development proceeds by the fibrous extracellular matrix acting as a scaffold for cells, inducing cell mi-gration and cell differentiation. Following this in vivo mechanism, we have developed an artificial extracellular matrix based on peptides with high biocompatibility that is expected to enable regeneration of brain organoids and neural tissues. Based on a proprietary peptide that forms highly homogeneous fibers and has cell adhesion properties, we have successfully developed the first material that induces angiogenesis in vivo by incorporating growth factor sustained release properties and enables recovery of injured brain after a single administration.細胞の全体像を可視化する高速・高分解能3D蛍光顕微鏡法の確立を目指し，技術開発を行った．まず，3D撮像の基本プラットフォームとしてライトシート顕微鏡法の一種である斜めライトシート顕微鏡法を採用し，これを高速化する像スキャン法を導入した．次に，高分解能化に向けた種々の検討を行った．顕微鏡ハードウエアに関しては，高分解能化の際に顕著に影響する装置の振動の影響を詳細に考察し，振動が撮像結果に与える影響を最小限するための設計指針を得，実際に効果を確認した．その一方でソフトウエア技術（画像処理）による高分解能化の検討も行い，深層学習ネットワークにより，低分解能画像から高分解能画像を取得する動作を数値シミュレーションにより確認した．We developed a technique to establish a high-speed, high-resolution 3D fluorescence microscopy method to visualize the entire image of a cell. First, oblique light-sheet microscopy, a type of light-sheet microscopy, was adopted as the basic platform for 3D imaging, and an image scanning method was introduced to speed up the process. Next, various studies were conducted to achieve higher resolution. Regarding the microscope hardware, we examined in detail the effects of vibration on the equipment, which is a significant factor in achieving high resolution, and obtained design guidelines to minimize the effects of vibration on the imaging results, and confirmed their effectiveness. On the other hand, we also examined the use of software technolo-gy (image processing) to achieve higher resolution, and confirmed the operation of acquiring a high-resolu-tion image from a low-resolution image using a deep learning network through numerical simulation.村岡 貴博34Takahiro MURAOKA三上 秀治35Hideharu MIKAMI超分子化学と神経科学の融合によるオルガノイド形成材料の開発（2021採択）Development of organoid-forming materials through the integration of supramolecular chemistry and neuroscience(Project 2021)細胞内ダイナミクスを明らかにする高速・高分解３D蛍光顕微鏡（2021採択）Development of high-speed, high-resolution 3D microscopy for revealing intracellular dynamics(Project 2021)41Rep. Grant. Res., Asahi Glass Foundation (2023)
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