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2011 Fiscal Year Final Research Report

Identification of paracrine factors from mesenchaymal stem cell for protection and treatment against lung injury

Research Project

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Project/Area Number 21590980
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionTohoku University

Principal Investigator

OHKOUCHI Shinya  東北大学, 病院, 助教 (40375035)

Co-Investigator(Kenkyū-buntansha) NUKIWA Toshihiro  東北大学, 大学院・医学系研究科, 名誉教授 (40129036)
Co-Investigator(Renkei-kenkyūsha) SAIJO Yasuo  新潟大学, 医学(系)研究科(研究院), 教授 (10270828)
Project Period (FY) 2009 – 2011
Keywords間葉系幹細胞 / Stanniocalcin1 / アポトーシス / 過酸化ストレス / Uncoupling Protein 2 / 嫌気性代謝 / Warburg効果 / 肺胞細胞
Research Abstract

Previous studies have demonstrated that mesenchymal stromal cells(MSCs)enhance cell survival through upregulation and secretion of stanniocalcin-1(STC1). This study shows that MSC-derived STC1 promotes survival of lung cancer cells by uncoupling oxidative phosphorylation, reducing intracellular reactive oxygen species(ROS), and shifting metabolism towards a more glycolytic metabolic profile. MSC-derived STC1 upregulated uncoupling protein 2(UCP2)in injured A549 cells in an STC1-dependent manner. Knockdown of UCP2 reduced the ability of MSCs and recombinant STC1(rSTC1)to reduce cell death in the A549 population. rSTC1-treated A549 cells displayed decreased levels of ROS, mitochondrial membrane potential(MMP), and increased lactate production, all of which were dependent on the upregulation of UCP2. Our data suggest that MSCs can promote cell survival by regulating mitochondrial respiration via STC1.

  • Research Products

    (14 results)

All 2012 2011 2010 2009

All Journal Article (4 results) (of which Peer Reviewed: 3 results) Presentation (3 results) Book (5 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Targeting lysophosphatidic Acid signaling retards culture-associated senescence of human marrow stromal cells2012

    • Author(s)
      Kanehira M, KikuchiT, Ohkouchi S, Shibahara T, Tode N, Santoso A, Daito H, Ohta H, Tamada T, Nukiwa T
    • Journal Title

      PLoS One

      Volume: 7(2) Pages: 32185

    • Peer Reviewed
  • [Journal Article] Mesenchymal stromal cells protect cancer cells from ROS-induced apoptosis and enhance the Warburg effect by secreting STC12012

    • Author(s)
      Ohkouchi S, Block GJ, Katsha AM, Kanehira M, Ebina M, Kikuchi T, Saijo Y, Nukiwa T, Prockop DJ
    • Journal Title

      Mol Ther

      Volume: 20(2) Pages: 417-23

    • DOI

      doi:10.1038/mt.2011.259

    • Peer Reviewed
  • [Journal Article] Paracrine Factors of Multipotent Stromal Cells Ameliorate Lung Injury in an Elastase-induced Emphysema Model2011

    • Author(s)
      Katsha AM, Ohkouchi S, Xin H, Kanehira M, Sun R, Nukiwa T, Saijo Y
    • Journal Title

      Molecular Therapy

      Volume: 19 1 Pages: 196-203

    • DOI

      doi:10.1038/mt

    • Peer Reviewed
  • [Journal Article] Gradual increase of high mobility group protein b1 in the lungs after the onset of acute exacerbation of idiopathic pulmonary fibrosis2011

    • Author(s)
      Ebina M, Ohkouchi S, Nukiwa T, et al
    • Journal Title

      Pulm Med

      Volume: 916486

  • [Presentation] STC1はUCP2誘導を介した過酸化ストレス軽減と非共役呼吸誘導をとおして、肺がん細胞の生存を誘導する2011

    • Author(s)
      大河内眞也、菊地利明、海老名雅仁、貫和敏博
    • Organizer
      日本癌学会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2011-10-05
  • [Presentation] Poster presentation ; Novel functions of stanniocalcin-1(STC1)through Uncoupling Protein 2(UCP2)up-regulation ; Promoting Survival of Cancer Cells under Oxidative Stress and Inducing the Uncoupling Respiration(Warburg effect)2011

    • Author(s)
      Shinya Ohkouchi, Toshiaki Kikuchi, Masahito Ebina, Toshihiro Nukiwa
    • Organizer
      欧州呼吸器学会年次集会
    • Place of Presentation
      オランダ、アムステルダムREI
    • Year and Date
      2011-09-25
  • [Presentation] 間葉系幹細胞(MSCs)分泌Stanniocalcin1(STC1)が誘導するUncouplingProtein2(UCP2)依存性ReactiveOxygenSpecies(ROS)抑制作用とWarburg効果2010

    • Author(s)
      大河内眞也, ahmed Katcha, 兼平雅彦, 菊地利明, 海老名雅仁, 貫和敏博
    • Organizer
      日本呼吸器学会学術総会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2010-04-21
  • [Book] 自己免疫性肺胞蛋白症の症例2011

    • Author(s)
      大河内眞也、海老名雅仁
    • Total Pages
      84-96
  • [Book] 肺気腫モデル2011

    • Author(s)
      大河内眞也
    • Total Pages
      490-498
    • Publisher
      羊土社
  • [Book] 特発性肺線維症臨床試験のエビデンス形成2010

    • Author(s)
      大河内眞也、貫和敏博
    • Total Pages
      100-104
    • Publisher
      ライフサイエンス出版
  • [Book] 典型的自己免疫性肺胞蛋白症症例の明確化に関する研究2010

    • Author(s)
      大河内眞也、貫和敏博
    • Total Pages
      115-121
  • [Book] 特発性間質性肺炎2009

    • Author(s)
      大河内眞也
    • Total Pages
      96-99
    • Publisher
      総合医学社
  • [Patent(Industrial Property Rights)] ケトーシス又はケトアシドーシス予防又は治療剤2011

    • Inventor(s)
      大河内眞也
    • Industrial Property Rights Holder
      国立大学法人東北大学
    • Industrial Property Number
      特許、2011-086926
    • Filing Date
      2011-01-12
  • [Patent(Industrial Property Rights)] 線維症予防又は治療用医薬組成物2011

    • Inventor(s)
      大河内眞也
    • Industrial Property Rights Holder
      国立大学法人東北大学
    • Industrial Property Number
      特許、2011-152392
    • Filing Date
      2011-02-10

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Published: 2013-07-31  

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