2021 Fiscal Year Final Research Report

Development of the 3D intervertebral disc tissue model reconstituted with its precursor cells and the tissue-specific mechanical environment

Research Project

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Project/Area Number	19K22954
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 90:Biomedical engineering and related fields
Research Institution	The University of Tokyo
Principal Investigator	Miura Shigenori 東京大学, 生産技術研究所, 特任講師 (70511244)
Co-Investigator(Kenkyū-buntansha)	宿南知佐広島大学, 医系科学研究科(歯), 教授 (60303905) 森本雄矢東京大学, 大学院情報理工学系研究科, 准教授 (60739233)
Project Period (FY)	2019-06-28 – 2022-03-31
Keywords	椎間板 / 力学刺激 / 線維輪 / BioMEMS / 生体模倣デバイス / Pax1 / 硬節 / 再生医療
Outline of Final Research Achievements	We have developed a stretching culture system for 3D tissue model of the intervertebral disc under the mechanical loading conditions as observed in the in vivo tissue. This culture system has a circular chamber structure for 3D culture of annulus fibrosus (AF) cells with the stretchable balloon at the center of the chamber. This balloon can be inflated by infusing air or liquid to mimic the deformation of the nucleus pulposus, caused by the mechanical loading on the spine. By exploring the best ECM components for 3D culture of AF cells, we could prepare a ring-shaped AF-like tissues through the cell-autonomous shrinkage process in our device. Interestingly, we found that stretching culture upregulated the genes to promote the fibrous tissue formation but suppressed the genes to induce cartilage differentiation. We believe our device is useful to reconstruct the fibrocartilaginous lamellar structure of the AF tissues.
Free Research Field	細胞生物学
Academic Significance and Societal Importance of the Research Achievements	椎間板を構成する線維輪構造の破綻は、椎間板ヘルニアをはじめとする種々の椎間板変性疾患を引き起こす。本研究では、椎間板組織に生じる力学刺激を模倣した培養デバイスを開発することで、3次元椎間板組織モデル構築のための培養技術の開発および椎間板線維輪細胞の力学刺激応答性について明らかにした。これらの基盤技術および知見は、椎間板の形成・成熟化に関わる分子メカニズムの解明および組織再生のための創薬スクリーニングなどに資するものと期待される。