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2015 Fiscal Year Annual Research Report

循環極少数細胞を標的とする閉鎖系高速細胞解析分離装置の開発

Planned Research

Project AreaHyper Bio Assembler for 3D Celluler Innovation
Project/Area Number 23106004
Research InstitutionThe University of Tokyo

Principal Investigator

中内 啓光  東京大学, 医科学研究所, 教授 (40175485)

Project Period (FY) 2011-04-01 – 2016-03-31
Keywords閉鎖系高速細胞解析分離装置 / 末梢循環がん細胞 / 赤芽球 / 血小板
Outline of Annual Research Achievements

我々はこれまでにフローサイトメトリーによって3万個に1個骨髄中に存在する造血幹細胞を再現性良く分離同定することに成功している。一方で,フローサイトメトリーによる細胞分離には,抗体を用いた体外での細胞染色ステップが必須であることや,機器のオペレーションでの極めて高い専門性など簡便性に劣る部分も指摘される。加えて,妊婦末梢血中の胎児由来有核赤血球細胞などの極めて低頻度(数十万~百万個に1個の頻度)でしか存在しない細胞を血液中で確実に同定し,十分な情報を得るためには理論上数百ml以上の血液を必要とし,その採取と体外操作は容易ではない。そこで本研究では体外循環方式の閉鎖系高速細胞解析分離装置の開発によって,血液を体外循環させながら個々の細胞を高速で解析することを目標に据えている。この体外循環システムではフローサイトメーター解析で用いられるような体外での細胞染色操作を行うことができない。そこで,簡便に細胞を選別するためのパラメーター検討したところ、これまでに、マイクロ流路通過速度の違い(細胞の粘度の違い)によってヒト末梢血中に混在する癌細胞株を明らかな細胞集団の違いでとらえることが出来た。さらに、ヒトiPS細胞から作製した赤芽球株を分化させ、成熟赤血球と比較したところ、粘度に大きな違いが見られた。また、マイクロ流路を利用して血管内のシェアストレスを再現することで、巨核球株から血小板の効率的な産生を実現することが出来た。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

  • Research Products

    (22 results)

All 2016 2015

All Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (14 results) (of which Int'l Joint Research: 14 results,  Invited: 14 results)

  • [Journal Article] Fetal Hematopoietic Stem Cell Transplantation Fails to Fully Regenerate the B-Lymphocyte Compartment.2016

    • Author(s)
      Ghosn EE, Waters J, Phillips M, Yamamoto R, Long BR, Yang Y, Gerstein R, Stoddart CA, Nakauchi H, Herzenberg LA
    • Journal Title

      Stem Cell Reports

      Volume: 6(1) Pages: 137-49

    • DOI

      10.1016/j.stemcr.2015.11.011

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche2016

    • Author(s)
      Chen JY, Miyanishi M, Wang SK, Yamazaki S, Sinha R, Kao KS, Seita J, Sahoo D, Nakauchi H, Weissman IL
    • Journal Title

      Nature

      Volume: 530(7589) Pages: 223-7

    • DOI

      10.1038/nature16943

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Circulating cells contribute to cardiomyocyte regeneration after injury2015

    • Author(s)
      Wu JM, Hsueh YC, Ch'ang HJ, Luo CY, Wu LW, Nakauchi H, Hsieh PC
    • Journal Title

      Circ Res

      Volume: 116(4) Pages: 633-41

    • DOI

      10.1161/CIRCRESAHA.116.304564

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation.2015

    • Author(s)
      Takebe T, Enomura M, Yoshizawa E, Kimura M, Koike H, Ueno Y, Matsuzaki T, Yamazaki T, Toyohara T, Osafune K, Nakauchi H, Yoshikawa HY, Taniguchi H
    • Journal Title

      Cell Stem Cell

      Volume: 16(5) Pages: 556-65

    • DOI

      10.1016/j.stem.2015.03.004

    • Peer Reviewed
  • [Journal Article] Novel strategies for liver therapy using stem cells2015

    • Author(s)
      Rashid T, Takebe T, Nakauchi H
    • Journal Title

      Gut

      Volume: 64(1) Pages: 1-4

    • DOI

      10.1136/gutjnl-2014-307480

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cell Adhesion Minimization by a Novel Mesh Culture Method Mechanically Directs Trophoblast Differentiation and Self-Assembly Organization of Human Pluripotent Stem Cells2015

    • Author(s)
      Okeyo KO, Kurosawa O, Yamazaki S, Oana H, Kotera H, Nakauchi H, Washizu M
    • Journal Title

      Tissue Eng Part C Methods

      Volume: 21(10) Pages: 1105-15

    • DOI

      10.1089/ten.TEC.2015.0038

    • Peer Reviewed
  • [Journal Article] Targeted organ generation using Mixl1-inducible mouse pluripotent stem cells in blastocyst complementation2015

    • Author(s)
      Kobayashi T, Kato-Itoh M, Nakauchi H
    • Journal Title

      Stem Cells Dev

      Volume: 24(2) Pages: 182-9

    • DOI

      10.1089/scd.2014.0270

    • Peer Reviewed
  • [Journal Article] Quantification of adult T-cell leukemia/lymphoma cells using simple four-color flow cytometry.2015

    • Author(s)
      Ishigaki T, Zaike Y, Nojima M, Kobayashi S, Ohno N, Uchimaru K, Tojo A, Nakauchi H, Watanabe N.
    • Journal Title

      Clin Chem Lab Med

      Volume: 53(1) Pages: 85-93

    • DOI

      10.1515/cclm-2014-0183

    • Peer Reviewed
  • [Presentation] Generation of Functional Organs by Way of Interspecific Blastocyst Complementation2016

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      Keystone Symposium
    • Place of Presentation
      Keystone, Colorado, USA
    • Year and Date
      2016-03-14
    • Int'l Joint Research / Invited
  • [Presentation] Novel cancer immunotherapy utilizing iPS cell technology2016

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      Siebel Stem Cell Symposium
    • Place of Presentation
      Stanford, CA, USA
    • Year and Date
      2016-01-20
    • Int'l Joint Research / Invited
  • [Presentation] Stem cell niche for cells and organs2016

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      Baxter Lab Retreat
    • Place of Presentation
      Menlo Park, CA, USA
    • Year and Date
      2016-01-20
    • Int'l Joint Research / Invited
  • [Presentation] “Organs, not Cells” Generation of Functional Organs from iPS Cells via Interspecies Blastocyst Complementation2015

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      Chinese Bioscience Association (CBA)
    • Place of Presentation
      Foster City, CA, USA
    • Year and Date
      2015-10-15
    • Int'l Joint Research / Invited
  • [Presentation] “Stem Cell Niche” From Cells to Organs and Beyond.”2015

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      Cincinnati Children's Hospital Research Foundation
    • Place of Presentation
      Cincinnati, OH, USA
    • Year and Date
      2015-10-07
    • Int'l Joint Research / Invited
  • [Presentation] Dietary created niche for non-myeloablative hematopoietic stem cell transplantation2015

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      International Society for Experimental Hematology (ISEH) 44th Annual Scientific Meeting
    • Place of Presentation
      京都国際会館(京都府京都市)
    • Year and Date
      2015-09-18
    • Int'l Joint Research / Invited
  • [Presentation] Growing New Organ in vivo2015

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      ESOT
    • Place of Presentation
      Brussels, Belgium.
    • Year and Date
      2015-09-15
    • Int'l Joint Research / Invited
  • [Presentation] Organs, not Cells: Toward the next generation of regenerative medicine2015

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      Hydra XI Summer School
    • Place of Presentation
      Hydra, Greece
    • Year and Date
      2015-09-12
    • Int'l Joint Research / Invited
  • [Presentation] Inter-species blastocyst complementation2015

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      TRANSGENIC ANIMAL RESEARCH CONFERENCE X (TARC)
    • Place of Presentation
      Tahoe City, CA, USA
    • Year and Date
      2015-08-12
    • Int'l Joint Research / Invited
  • [Presentation] Generation of Functional Organs from Pluripotent Stem Cells2015

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      University of Hawaii, the Institute for Biogenesis Research and the Office of Technology Transfer & Economic Development (IBR-OTTED) symposium
    • Place of Presentation
      Honolulu, Hawaii, USA
    • Year and Date
      2015-08-05
    • Int'l Joint Research / Invited
  • [Presentation] “Stem Cell Niche” From Cells to Organs and Beyond2015

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      ISSCR
    • Place of Presentation
      Stockholm, Sweden.
    • Year and Date
      2015-06-24
    • Int'l Joint Research / Invited
  • [Presentation] Generation of funcitonal organs in xenogeneic host using conceptus complementation2015

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      Recombinetics' Science Advisory Board
    • Place of Presentation
      Vieques, Puerto Rico
    • Year and Date
      2015-05-16
    • Int'l Joint Research / Invited
  • [Presentation] Generation of functional organs from iPS cells2015

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      UC Santa Barbara lecture series
    • Place of Presentation
      Santa Barbara, CA, USA
    • Year and Date
      2015-05-05
    • Int'l Joint Research / Invited
  • [Presentation] Organ niches and developmental complementation for generation of functional organs in vivo2015

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      8th International Meeting of the Stem Cell Network North Rhine Westphalia
    • Place of Presentation
      Bonn, Germany
    • Year and Date
      2015-04-21
    • Int'l Joint Research / Invited

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Published: 2017-01-06  

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