Development of on-chip vascular model utilizing the self-organizing ability: reconstitution-based understanding of vascular physiology and pathology

• Project/Area Number: 26670394
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kumamoto University
• Principal Investigator: Nishiyama Koichi 熊本大学, 医学部附属病院, 講師 (80398221)
• Co-Investigator(Renkei-kenkyūsha): MIURA Takashi 九州大学, 大学院医学系研究院, 教授 (10324617) ; YOKOKAWA Ryuji 京都大学, 大学院工学系研究科, 准教授 (10411216)
• Research Collaborator: MATSUBARA Akira ; KUNITA Itsuki
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 血管新生 / 微小流体デバイス / 自己組織化 / 再構成 / 血流 / 分化

Outline of Final Research Achievements

In this study, we developed a fundamental technology, which enables to reconstiute the long-term-perfusable vascualr network on a microfluidic device via angiogenesis. Using either human or murine primary cells, we succeeded to reconstruct the vascualr strucutre that approsimates in vivo, in which endothelial sprouts were properly covered with perivascular pericytes and have a lumen structure. Furthermore, the reconstructed vasculature was perfusable with the culture media at a perfusion speed, corresponding to capillary blood flow, over a week. In addition, we established an imaging and quatitative analysis system for understanding of cellular angiogenic mechanisms. Using the on-chip angiogenic model, we identified intraluinal pressure to be one of the potential negative regulators of endothelial cell-driven aniogenesis.

Research Products

• [Journal Article] Autonomy and non-autonomy of angiogenic cell movements revealed by experiment-driven mathematical modeling (2015)
  • Author(s): Sugihara K, Nishiyama K, Fukuhara S, Uemura A, Arima S, Kobayashi R, Kohn-Luque A, Mochizuki N, Suda T, Ogawa S, Kurihara H
  • Journal Title: Cell Rep Volume: 13 Issue: 9 Pages: 1814-1827
  • DOI: 10.1016/j.celrep.2015.10.051
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The accuracy of central blood pressure waveform by novel mathematical transformation of non-invasive measurement. (2015)
  • Author(s): Sueta D, Yamamoto E, Tanaka T, Hirata Y, Sakamoto K, Tsujita K, Kojima S, Nishiyama K, Kaikita K, Hokimoto S, Jinnouchi H and Ogawa H.
  • Journal Title: Int J Cardiol Volume: 189 Pages: 244-246
  • DOI: 10.1016/j.ijcard.2015.03.182
  • Peer Reviewed
• [Journal Article] Myocardium-derived angiopoietin-1 is essential for coronary vein formation in the developing heart (2014)
  • Author(s): Arita Y, Nakaoka Y, Matsunaga T, Kidoya H, Yamamizu K, Arima Y, Kataoka-Hashimoto T, Ikeoka K, Yasui T, Masaki T, Yamamoto K, Higuchi K, Park JS, Shirai M, Nishiyama K, Yamagishi H, Otsu K, Kurihara H, Minami T, Yamauchi-Takihara K, Koh GY, Mochizuki N, Takakura N, Sakata Y, Yamashita JK, Komuro I
  • Journal Title: Nat Commun Volume: 5 Issue: 1 Pages: 4452-4452
  • DOI: 10.1038/ncomms5552
  • Peer Reviewed / Open Access
• [Journal Article] 血管づくりに秘められた細胞集団の挙動 (2014)
  • Author(s): 西山功一
  • Journal Title: 細胞工学 Volume: 33(6) Pages: 639-644
• [Presentation] 自律的に樹状構造をつくる血管細胞動態と制御機構 (2016)
  • Author(s): 西山功一
  • Organizer: 第１２１回日本解剖学会総会・全国学術集会 シンポジウム「形作りのダイナミクスとその制御機構の探索～新たな発生原理の解明を目指して」
  • Place of Presentation: ビッグパレットふくしま（福島）
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] Quantification of effects of mechanical stimuli and mural cells on angiogenic morphogenesis (2016)
  • Author(s): Kunita I, Nishiyama K
  • Organizer: National Institute of Genetics International Symposiumm 2016
  • Place of Presentation: 東大産総研（東京）
  • Year and Date: 2016-01-10
  • Int'l Joint Research
• [Presentation] 血管新生における血管壁細胞の役割 (2015)
  • Author(s): 西山功一
  • Organizer: CVMW2015 心血管代謝週間 シンポジウム「血管・リンパ管のpericascular cell の多面的機能を理解する」
  • Place of Presentation: 神戸国際会議場（神戸）
  • Year and Date: 2015-12-12
  • Invited
• [Presentation] 血管新生に対する力学刺激の効果を検証するための灌流アッセイ系の構築 (2015)
  • Author(s): 國田 樹、 梨本裕司、中益朗子、中山雅宗、鳥澤 勇介、横川 隆司、三浦 岳、西山 功一
  • Organizer: CVMW2015 心血管代謝週間
  • Place of Presentation: 神戸国際会議場（神戸）
  • Year and Date: 2015-12-10
• [Presentation] 血管内皮細胞の血管新生運動を制御する細胞自律的・非自律的メカニズム (2015)
  • Author(s): 西山功一、國田 樹
  • Organizer: CVMW2015 心血管代謝週間
  • Place of Presentation: 神戸国際会議場（神戸）
  • Year and Date: 2015-12-10
• [Presentation] 血管新生プレイヤーとしてのペリサイト (2015)
  • Author(s): 西山功一
  • Organizer: 第38回年会（BMB2015）ワークショップ「周皮細胞（ペリサイト）の病態生理学的重要性」
  • Place of Presentation: 神戸商工会議所（神戸）
  • Year and Date: 2015-12-02
  • Invited
• [Presentation] Coordinated angiogenic behavior of tip endothelial cell revealed by a combined approach with experiment and mathematical modeling (2015)
  • Author(s): Nishiyama K, Sugihara K, Fukuhara S, Kunita I, Uemura A, Arima S, Kobayashi R, Kohn-Luque A and Kurihara H.
  • Organizer: 第13回日韓血管生物合同シンポジウム
  • Place of Presentation: サムジュアートホール（釜山、韓国）
  • Year and Date: 2015-10-15
  • Int'l Joint Research
• [Presentation] Coordinated angiogenic behavior of tip cell revealed by experiment-driven mathematical modeling (2015)
  • Author(s): Nishiyama K, Sugihara K, Fukuhara S, Uemura A, Arima S, Kobayashi R, Kohn-Luque A, Mochizuki N, Suda T, Ogawa H and Kurihara H.
  • Organizer: Gordon conference 'angiogenesis'
  • Place of Presentation: サルベ・レジナ大学（ロードアイランド、米国）
  • Year and Date: 2015-08-05
  • Int'l Joint Research
• [Presentation] Genetic and epigenetic regulation in angiogenic cell dynamics (2015)
  • Author(s): 西山功一、小川久雄
  • Organizer: 第79回日本循環器学会学術集会・会長特別企画「エピゲノムと循環器疾患」
  • Place of Presentation: リーガロイヤルホテル（大阪）
  • Year and Date: 2015-04-26
  • Invited
• [Presentation] Molecular and cellular mechanisms in angiogenic morphogenesis (2015)
  • Author(s): 西山功一、小川久雄
  • Organizer: 第79回日本循環器学会学術集会・ラウンドテーブルディスカッション「分子画像による病態解明」
  • Place of Presentation: リーガロイヤルホテル（大阪）
  • Year and Date: 2015-04-24
  • Invited
• [Presentation] VASCULAR NETWORK FORMATION FOR A LONG-TERM SPHEROID CULTURE BY CO-CULTURING ENDOTHELIAL CELLS AND FIBROBLASTS (2015)
  • Author(s): Tomoya Hayashi, Hisako Takigawa-Imamura, Koichi Nishiyama, et al.
  • Organizer: The 28th IEEE International Conference on Micro Electro Mechanical Systems (MEMS 2015)
  • Place of Presentation: Estoril Centro De Congressos (Estoril)
  • Year and Date: 2015-01-18 – 2015-01-22
• [Presentation] 血管新生の包括的理解のための新しい解析システムの構築 (2014)
  • Author(s): 西山 功一
  • Organizer: 第５回Molecular Cardiovascular Conference II
  • Place of Presentation: 神戸ベイシェラトンホテル（神戸）
  • Year and Date: 2014-08-06
• [Presentation] Cell Dynamics During Angiogenic Morphogenesis (2014)
  • Author(s): 西山 功一
  • Organizer: The Joint Annual Meeting of the Japanese Society for Mathematical Biology and the Society for Mathematical Biology
  • Place of Presentation: コンベンションセンター（大阪）
  • Year and Date: 2014-08-01
  • Invited
• [Presentation] Stochastic and deterministic aspects of angiogenic endothelial cell movements revealed by mathematical modelling (2014)
  • Author(s): 西山 功一
  • Organizer: Research PlaNet 2014
  • Place of Presentation: 東京国際フォーラム（東京）
  • Year and Date: 2014-05-10
  • Invited
• [Presentation] Stochastic and deterministic aspects driving angiogenesis as a morphogenetic multicellular movement (2014)
  • Author(s): 西山 功一
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: みやこめっせ（京都）
  • Year and Date: 2014-04-17
  • Invited
• [Remarks] 熊本大学国際先端医学研究機構(IRCMS)・西山研究室ホームページ
  • URL: http://kumamoto-ircms-nishiyama.jp/about-research/
• [Remarks] 熊本大学国際先端医学研究拠点施設 西山研究室ホームページ
  • URL: http://ircms.kumamoto-u.ac.jp/research/archives/6