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Modeling the neural impact of maternal immune modulation using human induced pluripotent stem cells.

Research Project

Project/Area Number 15K09719
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

MASAFUMI MORIMOTO  京都府立医科大学, 医学部, 教授 (10285265)

Co-Investigator(Kenkyū-buntansha) 千代延 友裕  京都府立医科大学, 医学(系)研究科(研究院), 助教 (40571659)
Research Collaborator ZUIKI Masashi  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsiPS 細胞 / インターロイキン6 / 神経分化 / 神経凝集体 / ルテオリン
Outline of Final Research Achievements

We induced differentiation of iPS cells derived from healthy individuals into neuroectodermal cells. We then cultured these iPS cells in suspension cultures to obtain neuronal aggregates. Based on the shift of neuronal cell markers, we confirmed that these neuronal aggregates were emulating the cerebral cortex. When we exposed this fetal brain model to interleukin-6 (IL-6) for 24 hours, we observed increased levels of phosphorylated signal transducer and activator of transcription 3 (STAT3). Ten days later, we found increased levels of astrocytes and a reduction in neuronal cells. Simultaneous administration of luteolin downregulated the phosphorylation of STAT3 and inhibited the attenuation in neuronal differentiation induced by IL-6. We believe the neuronal system model used in this study can greatly contribute to the pathophysiological analysis and treatment discovery in fetal encephalopathy caused by the fetal environment.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (3 results)

All 2017 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Luteolin attenuates interleukin-6-mediated astrogliosis in human iPSC-derived neural aggregates: A candidate preventive substance for maternal immune activation-induced abnormalities2017

    • Author(s)
      Zuiki Masashi、Chiyonobu Tomohiro、Yoshida Michiko、Maeda Hiroshi、Yamashita Satoshi、Kidowaki Satoshi、Hasegawa Tatsuji、Gotoh Hitoshi、Nomura Tadashi、Ono Katsuhiko、Hosoi Hajime、Morimoto Masafumi
    • Journal Title

      Neuroscience Letters

      Volume: 653 Pages: 296-301

    • DOI

      10.1016/j.neulet.2017.06.004

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ルテオリンはIL-6による神経分化障害を改善するーヒトiPS細胞を用いた母体炎症による胎児脳障害の治療探索2017

    • Author(s)
      瑞木匡、千代延友裕、前田裕史、山下哲史、吉田路子、長谷川龍志、森本昌史
    • Organizer
      第59回日本小児神経学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Modeling the neural impact of maternal immune activation using human induced pluripotent stem cells.2016

    • Author(s)
      Zuiki M, Chiyonobu T, Yoshida M, Kidowaki S, Yamashita S, Hasegawa T, Morimoto M.
    • Organizer
      The 14th International Child Neurology Congress
    • Place of Presentation
      Amsterdam, the Netherlands
    • Year and Date
      2016-05-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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