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Development of a microdevice for the study of the interaction between endothelial cells and neuronal cells

Research Project

Project/Area Number 16K17501
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Nano/Microsystems
Research InstitutionKyoto University (2017)
The University of Tokyo (2016)

Principal Investigator

Okeyo Kennedy Omondi  京都大学, ウイルス・再生医科学研究所, 特定講師 (10634652)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords3次元共培養デバイス / 血管ー神経相互作用 / 血液脳関門 / メッシュ培養技術 / 細胞間相互作用 / 密着結合 / マイクロメッシュ培養法 / 異種細胞間相互作用 / 物質輸送
Outline of Final Research Achievements

The blood brain barrier (BBB) is barrier which strictly regulates the transport of substances into the brain, thereby contributing to the maintenance of brain homeostasis. Because BBB is highly selective, most molecules, including many promising drug candidates, cannot enter into the brain space from the blood, hindering the development of drugs for neurodegenerative diseases such as Alzheimer. Although the mechanism for the selective transport of BBB remains unknown, it is thought to be modulated by the interaction between endothelial cells and brain cells, specifically, astrocytes. In this study, employing our novel technology of micromesh culture, we focused on developing a microdevice which emulates the basic components of in vivo BBB for application in the study of the interaction between endothelial cells and brain cells (neural cells). Endothelial cell sheets were generated and a co-culture system established for future application to the study of BBB functionality.

Academic Significance and Societal Importance of the Research Achievements

脳内環境は有害物質によって乱されると脳細胞の活動が阻害され,神経変性疾患の発端となる.このため,血液脳関門(BBB)という組織によって守られている.BBBは,脳内毛細血管を構成する内皮細胞が密着結合を形成し,血液から脳内への物質の出入を厳しく制限することで,脳内環境を安定に維持している.しかし,この厳しい物質通過の制限のせいで神経変性疾患をターゲットに開発された薬の殆どが失敗に終わっている.本研究は,このBBBの仕組み理解に役立つモデルを構築し,さらにそれを用いてBBBの働きである選択的物質輸送の仕組みを調べた.将来的には,このモデルを使って事前にBBBを通過できる薬の開発や評価に役立てたい.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (22 results)

All 2018 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (18 results) (of which Int'l Joint Research: 17 results,  Invited: 4 results)

  • [Journal Article] Nucleosomes exhibit non-uniform unwrapping along native chromatin fibers with increasing salt concentration as revealed by direct imaging in a microfluidic channel2018

    • Author(s)
      Hiroki Mori, Kennedy Omondi Okeyo, Masao Washizu and Hidehiro Oana
    • Journal Title

      Biotechnology Journal

      Volume: 13 Issue: 1 Pages: 1-8

    • DOI

      10.1002/biot.201700245

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Self-organization of human iPS cells into trophectoderm mimicking cysts induced by adhesion restriction using microstructured mesh scaffolds2018

    • Author(s)
      Kennedy O. Okeyo, Maiko Tanabe, Osamu Kurosawa, Hidehiro Oana, Masao Washizu
    • Journal Title

      Development, Growth & Differentiation

      Volume: 0 Issue: 3 Pages: 1-13

    • DOI

      10.1111/dgd.12430

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Minimization of cell-substrate interaction using suspended microstructured meshes initiates cell sheet formation by selfassembly organization2016

    • Author(s)
      Kennedy Omondi Okeyo, Osamu Kurosawa, Hidehiro Oana, Hidetoshi Kotera and Masao Washizu
    • Journal Title

      Biomed. Phys. Eng. Express

      Volume: 2 Issue: 6 Pages: 065019-065019

    • DOI

      10.1088/2057-1976/2/6/065019

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Adhesion patterning by a novel air-lock technique enables localization and in-situ real-time imaging of reprogramming events in one-to-one electrofused hybrids2016

    • Author(s)
      Shota Sakamoto, Kennedy Okeyo, Satoshi Yamazaki, Osamu Kurosawa, Hidehiro Oana, Hidetoshi Kotera, and Masao Washizu
    • Journal Title

      Bio microfluidics

      Volume: 10(5) Issue: 5

    • DOI

      10.1063/1.4965422

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Direct observation-based analysis of compaction stability of individual chromosomes isolated from single mammalian cells2017

    • Author(s)
      (1)Hidehiro Oana, Tomohiro Takahashi, Kennedy O. Okeyo , Jun Ueda, Masao Washizu
    • Organizer
      MicroTAS 2017, October 22-26, Savannah, Atlanta USA.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Induction of stem cell self-assembly by adhesion restriction, Lab-on-a-Chip, Microfluidics & Biosensors Asia 20172017

    • Author(s)
      Kennedy O. Okeyo,
    • Organizer
      November 30- December 1, 2017, Taipei, Taiwan.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Integrating Microfluidics and Tissue Engineering for Organ-on-a Chip Applications2017

    • Author(s)
      Kennedy O. Okeyo
    • Organizer
      , Lab-on-a-Chip and Microfluidics World Congress 2017, Coronado Island, California, USA. Octocber, 2-4, 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Novel micromesh culture method enables self-assembly cell sheet formation and mechanotransduction,2017

    • Author(s)
      Osamu Kurosawa, Kennedy O. Okeyo, H. Iwata, and M. Washizu
    • Organizer
      International Symposium on Nanomedicine 2017, School of Medicine Centennial Hall, Tohoku University, Sendai, Japan. December 13-15, 2017.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Direct observation-based analysis of compaction stability of individual chromosomes isolated from single mammalian cells2017

    • Author(s)
      Hidehiro Oana, Tomohiro Takahashi, Kennedy O. Okeyo , Jun Ueda, Masao Washizu,
    • Organizer
      MiroTAS 2017, October 22-26, Savannah, Atlanta USA.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Basic Study of iPS Cell Culture Substrate by using Metal Micro Mesh Device2017

    • Author(s)
      Maiko Tanabe, Kennedy O. Okeyo, Masahiro Okanojo, Hiroko Hanzawa, Masao Washizu, Shizu Takeda
    • Organizer
      Lab-on-a-Chip and Microfluidics World Congress 2017, Coronado Island, California, USA. Octocber, 2-4, 2017.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Self-organized Morphological Changes in ES Cells on Adhesion-restricted Substrates2017

    • Author(s)
      Yuta Ando, Kennedy O. Okeyo, and Taiji Adachi
    • Organizer
      5th Switzerland-Japan Workshop on Biomechanics (SJB2017), Zermatt, Switzerland, September, 14-17, 2017.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fabrication of in vitro tissue/organ models for disease modeling and drug development2017

    • Author(s)
      Kennedy O. Okeyo
    • Organizer
      , The 3rd Africa International Biotechnology and Biomedical Conference (AIBBC 2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マイクロメッシュを基板とする共培養システムを用いた生体内組織挙動の再現2017

    • Author(s)
      オケヨ・ケネディ・オモンディ,山田快,小穴英廣,鷲津正夫
    • Organizer
      第34回「センサ・マイクロマシンと応用システム」シンポジウム,広島国際会議場,広島市,2017年,10 月 31 日―11 月 2 日
    • Related Report
      2017 Annual Research Report
  • [Presentation] Optical Mapping of Epigenetic Information along Intact Chromatin Fibers isolated from Single Cells in a Microchannel2016

    • Author(s)
      (1)Tomohiro Takahashi, Kennedy O. Okeyo, Masao Washizu, Jun Ueda, Hidehiro Oana
    • Organizer
      International Symposium on Micro-Nano Science and Technology
    • Place of Presentation
      The University of Tokyo, Hongo Campus, Tokyo Japan
    • Year and Date
      2016-12-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Fabrication of bilayer cell sheet structures with direct cross-layer cell-cell contact using the mesh culture technique2016

    • Author(s)
      Kai Yamada, Kennedy O. Okeyo, Osamu Kurosawa, Hidehiro Oana, and Masao Washizu
    • Organizer
      International Symposium on Micro-Nano Science and Technology
    • Place of Presentation
      The University of Tokyo, Hongo Campus, Tokyo, Japan
    • Year and Date
      2016-12-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Direct Acquisition of Epigenetic Information along Chromatin Fibers Isolated from Single Mammalian Cell2016

    • Author(s)
      Tomohiro Takahashi, Kennedy O. Okeyo, Masao Washizu, Hidehiro Oana
    • Organizer
      International Conference on Single Cell Research
    • Place of Presentation
      The University of Tokyo, Hongo Campus,Tokyo, Japan
    • Year and Date
      2016-11-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Fabrication of freely standing oriented myotubes using a novel mesh culture method and analysis of calcium dynamics for functionality assay2016

    • Author(s)
      Kennedy O. Okeyo, Miku Azeyanagi, Osamu Kurosawa, Hidehiro Oana, and Masao Washizu
    • Organizer
      The 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences
    • Place of Presentation
      Dublin, Ireland
    • Year and Date
      2016-10-09
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Live imaging of somatic nuclear reprogramming using an electrofusion microfluidic device with air-lock patterned adhesion areas for fusant localization,2016

    • Author(s)
      Shota Sakamoto, Kennedy O. Okeyo, Osamu Kurosawa, Hidehiro Oana, and *Masao Washizu
    • Organizer
      The 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences
    • Place of Presentation
      Dublin, Ireland
    • Year and Date
      2016-10-09
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Direct Observation of Epigenetic Modifications along Intact Chromatin Fibers of Individual Chromosomes Isolated from Single Cells in a Microfluidic Channel2016

    • Author(s)
      Tomohiro Takahashi, Kennedy O. Okeyo, Masao Washizu, Jun Ueda, Hidehiro Oana
    • Organizer
      The 2016 International Conference on Solid State Devices and Materials (SSDM2016)
    • Place of Presentation
      Tsukuba International Congress Center, Tsukuba, Japan
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Step by step fabrication of biomaterials based on cell adhesion control2016

    • Author(s)
      Kennedy Omondi Okeyo
    • Organizer
      Lab-on-a-Chip, Microfluidics & Microarrays World Congress
    • Place of Presentation
      San Diego, California, USA
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanical induction of trophoblast-like differentiation in human iPS cells2016

    • Author(s)
      Kennedy O. Okeyo, Osamu Kurosawa, Satoshi Yamazaki, .Hidehiro Oana, Hidetoshi Kotera, Hiromitsu Nakauchi, and Masao Washizu
    • Organizer
      Cell Symposium, 10 years of iPSCs
    • Place of Presentation
      Berkeley, California, USA.
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The shoji technique for cell adhesion control and fabrication of cell sheets2016

    • Author(s)
      (2)Kennedy O. Okeyo, Kai Yamada, Rina Yanaru, Osamu Kurosawa, Hidehiro Oana, and Masao Washizu
    • Organizer
      The 77 Japan Society of Applied Physics Autumn Meeting
    • Place of Presentation
      Toki Messe, Niigata City, Japan
    • Year and Date
      2016-09-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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