Spatio-temporal control of cellular microenvironment to direct collective cell formation

• Project/Area Number: 15H05512
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Intelligent mechanics/Mechanical systems
• Research Institution: Osaka Prefecture University
• Principal Investigator: Hagiwara Masaya 大阪府立大学, 研究推進機構, 講師 (00705056)
• Research Collaborator: Kawahara Tomohiro 九州工業大学, 大学院生命体工学研究科 (20575162)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥24,440,000 (Direct Cost: ¥18,800,000、Indirect Cost: ¥5,640,000); Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2015: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
• Keywords: 細胞環境制御 / 反応拡散モデル / 細胞行動 / 気管支上皮細胞 / 細胞集団形成 / 培養環境制御 / 三次元培養 / 気管支分岐形成 / マイクロナノ / 細胞・組織 / 培養制御 / 自律形成制御 / パターン形成 / 培養環境 / 気管支 / 微細加工 / マイクロ流体チップ

Outline of Final Research Achievements

We have achieved to develop an in vitro - in silico interface platform for elucidating the logic of multicellular pattern formation. Two-dimensional collective cell pattern formation was achieved using only normal human bronchial epithelial cells. Then, simple microfabrication techniques followed by feedback iteration were used to bridge the gap between the mathematical model and in vitro experiments. The mechanisms underlying pattern formation of bronchial epithelial cells were evaluated using a reaction-diffusion model. The results indicated that long-range inhibition and short-range activation systems determine the direction of collective cell migration to form a specific pattern.

Research Products

• [Journal Article] Large Scale Imaging by Fine Spatial Alignment of Multi-Scanning Data with Gel Cube Device (2018)
  • Author(s): Masaya Hagiwara, Rina Nobata, Tomohiro Kawahara
  • Journal Title: Applied Science Volume: 8 Issue: 2 Pages: 1-10
  • DOI: 10.3390/app8020235
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] In Vitro Experimental Model for the Long-Term Analysis of Cellular Dynamics During Bronchial Tree Development from Lung Epithelial Cells (2017)
  • Author(s): Masaya Hagiwara, Naomichi Maruta, Moegi Marumoto
  • Journal Title: Tissue Engineering Part C Volume: 23 Issue: 6 Pages: 323-332
  • DOI: 10.1089/ten.tec.2017.0126
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tissue in Cube: In Vitro 3D Culturing Platform with Hybrid Gel Cubes for Multi-Directional Observations (2016)
  • Author(s): Masaya Hagiwara, Tomohiro Kawahara, Rina Nobata
  • Journal Title: Advanced Healthcare Materials Volume: 印刷中 Issue: 13 Pages: 1566-1571
  • DOI: 10.1002/adhm.201600167
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] An in vitro - in silico interface platform for spatiotemporal analysis of pattern formation in collective epithelial cells (2016)
  • Author(s): Masaya Hagiwara
  • Journal Title: Integrative Biology Volume: 8 Issue: 8 Pages: 861-868
  • DOI: 10.1039/c6ib00073h
  • Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] In vitro 3D Culture Platform for Large-Scale Imaging by Hybrid Gel Cube (2017)
  • Author(s): Masaya Hagiwara, Rina Nobata, Tomohiro Kawahara
  • Organizer: 12th IEEE International Conference on Nano/Micro Engineered and Molecular System
  • Place of Presentation: University of California, Los Angeles
  • Year and Date: 2017-03-10
  • Int'l Joint Research
• [Presentation] 分岐形態形成システム解明に向けた3次元培養プラットフォームの構築 (2017)
  • Author(s): 萩原将也，野畑李奈，川原知洋
  • Organizer: 第29回バイオエンジニアリング講演会
  • Place of Presentation: ウインク名古屋
  • Year and Date: 2017-01-19
• [Presentation] 上皮細胞集団間相互作用におけるパターン形成解析 (2017)
  • Author(s): 白石大和、丸本萌、萩原将也
  • Organizer: 第29回バイオエンジニアリング講演会
  • Place of Presentation: ウインク名古屋
  • Year and Date: 2017-01-19
• [Presentation] In vitro 3D Culture Platform for Large-Scale Imaging by Hybrid Gel Cube (2017)
  • Author(s): M. Hagiwara, R. Nobata, T. Kawahara
  • Organizer: 12th IEEE International Conference on Nano/Micro Engineered and Molecular Systems
  • Int'l Joint Research
• [Presentation] WHERE CELLS GO: DEVELOPING MECHANOCHEMICAL HYBRID MODEL OF COLLECTIVE CELL MIGRATION TOWARD DIRECTING COMPLEX TISSUE FORMATION (2017)
  • Author(s): Moegi Marumoto, Yamato Shiraishi, Masaya Hagiwara
  • Organizer: 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences (mTAS 2017)
  • Int'l Joint Research
• [Presentation] IN VITRO 3D CULTURE PLATFORM ENABLING 3D CELL CONSTRUCTION WITH WHOLE TISSUE IMAGING (2017)
  • Author(s): Rina Nobata, Tomohiro Kawahara, Masaya Hagiwara
  • Organizer: 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences (mTAS 2017)
  • Int'l Joint Research
• [Presentation] In vitro三次元培養における制御・イメージングプラットフォームの構築 (2017)
  • Author(s): 野畑李奈, 川原知洋, 萩原将也,
  • Organizer: 第35回化学とマイクロナノシステム学会
• [Presentation] 組織形成における細胞行動決定システム解析のための力学-化学ハイブリッドモデルの構築 (2017)
  • Author(s): 丸本萌, 白石大和, 萩原将也
  • Organizer: 第35回化学とマイクロナノシステム学会
• [Presentation] Dynamic Analysis of Collective Cell Migration by Mechanochemical Hybrid Model (2017)
  • Author(s): Moegi Marumoto, Masaya Hagiwara
  • Organizer: 第55回生物物理学会年会
• [Presentation] In vitro 3D culture platform for environmental control and imaging (2017)
  • Author(s): Masaya Hagiwara, Rina Nobata, Tomohiro Kawahara
  • Organizer: 第55回生物物理学会年会
• [Presentation] ３D培養環境制御・計測プラットフォームによる気管支分岐形成解析 (2017)
  • Author(s): 萩原将也，野畑李奈
  • Organizer: 「細胞を創る」研究会１０．０
  • Invited
• [Presentation] 組織形成システム制御に向けた細胞行動モデルの構築 (2017)
  • Author(s): 萩原将也，丸本萌
  • Organizer: 第60回自動制御連合会講演会
• [Presentation] パターン形成制御に向けた細胞行動決定システム解析 (2017)
  • Author(s): 丸本萌，白石大和，萩原将也
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] 三次元培養制御計測を可能にする多機能Cube型プラットフォームの構築 (2017)
  • Author(s): 野畑李奈，川原知洋，萩原将也
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] 二次元培養条件制御による細胞集団と個体の行動解析 (2016)
  • Author(s): 丸本萌，白石大和，萩原将也
  • Organizer: 第39回分子生物学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] In vitro 3D culture platform for multidirectional imaging (2016)
  • Author(s): M. Hagiwara, R. Nobata, T. Kawahara
  • Organizer: RCS Tokyo International
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2016-09-08
  • Int'l Joint Research
• [Presentation] 多面観察プラットフォームによる細胞組織の大域高解像イメージング (2016)
  • Author(s): 萩原 将也, 野畑 李奈, 川原 知洋
  • Organizer: 第34回化学とマイクロナノシステム学会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2016-09-06
• [Presentation] 培養環境制御による細胞集団間コミュニケーション解析 (2016)
  • Author(s): 白石 大和, 萩原 将也
  • Organizer: 第34回化学とマイクロナノシステム学会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2016-09-06
• [Presentation] Tissue in Cube: ハイブリッドゲルによる三次元細胞組織培養プラトフォーム (2016)
  • Author(s): 萩原将也、川原知洋、野畑李奈
  • Organizer: 第33回化学とマイクロナノシステム学会
  • Place of Presentation: 東京大学生産技術研究所（東京都目黒区）
  • Year and Date: 2016-04-25
• [Presentation] In vitro 3D culturing platform with Omni-directional imaging device (2016)
  • Author(s): Masaya Hagiwara, Tomohiro Kawahara
  • Organizer: CDB Symposium 2016, Size in Development
  • Place of Presentation: Riken CDB, Kobe, Japan
  • Year and Date: 2016-03-28
  • Int'l Joint Research
• [Presentation] 細胞位置制御による細胞組織の分岐発達メカニズム解析 (2016)
  • Author(s): 萩原将也、白石大和
  • Organizer: 第28回バイオエンジニアリング講演会
  • Place of Presentation: 東京工業大学（東京都目黒区）
  • Year and Date: 2016-01-10
• [Presentation] 培養初期条件制御による気管支上皮細胞の二次元分岐形成メカニズム解析 (2015)
  • Author(s): 萩原将也
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 気管支上皮細胞の三次元分岐再構成における異種細胞が与える影響解析 (2015)
  • Author(s): 丸田尚道、原田直樹、萩原将也
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Spatio-temporal analysis of lung branching morphogenesis by controlling two-dimensional cell positions (2015)
  • Author(s): Masaya Hagiwara
  • Organizer: The 26th CDB Meeting, Mechanical Perspectives of Multicellular Organization
  • Place of Presentation: Riken CDB, Kobe, Japan
  • Year and Date: 2015-09-08
  • Int'l Joint Research
• [Remarks] 研究室URL
  • URL: http://www.nanosq.21c.osakafu-u.ac.jp/ttsl_lab/m_hagiwara/index.html
• [Patent(Industrial Property Rights)] 細胞培養用流体チップ (2018)
  • Inventor(s): 萩原将也
  • Industrial Property Rights Holder: 萩原将也
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
  • Overseas
• [Patent(Industrial Property Rights)] 細胞培養容器、観察用試料セルおよび細胞培養方法： (2017)
  • Inventor(s): 萩原将也、川原知洋
  • Industrial Property Rights Holder: 萩原将也、川原知洋
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017
  • Overseas
• [Patent(Industrial Property Rights)] 細胞培養用流体チップ (2017)
  • Inventor(s): 萩原将也
  • Industrial Property Rights Holder: 萩原将也
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017-02-09
• [Patent(Industrial Property Rights)] 細胞培養容器、観察用試料セルおよび細胞培養方法 (2017)
  • Inventor(s): 萩原将也，川原知洋
  • Industrial Property Rights Holder: 萩原将也，川原知洋
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017-02-15
• [Patent(Industrial Property Rights)] 細胞培養容器及び観察用試料セル (2016)
  • Inventor(s): 萩原将也，川原知洋
  • Industrial Property Rights Holder: 萩原将也，川原知洋
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-11-07
  • Overseas
• [Patent(Industrial Property Rights)] 細胞培養容器及び観察用試料セル (2015)
  • Inventor(s): 萩原将也、川原知洋
  • Industrial Property Rights Holder: 大阪府立大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-12-04