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

Research Project

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
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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 / 肺胞上皮細胞 / 過酸化 / Uncoupling Protein2
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.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (26 results)

All 2012 2011 2010 2009

All Journal Article (8 results) (of which Peer Reviewed: 7 results) Presentation (9 results) Book (6 results) Patent(Industrial Property Rights) (3 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: 32185-32185

    • Related Report
      2011 Final Research Report
    • 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) Issue: 2 Pages: 417-23

    • DOI

      10.1038/mt.2011.259

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Targeting lysophosphatidic acid signaling retards culture-associated senescence of human marrow stromal cells2012

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

      PLoS One

      Volume: 7 Issue: 2 Pages: e32185-e32185

    • DOI

      10.1371/journal.pone.0032185

    • Related Report
      2011 Annual Research Report
    • 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

    • Related Report
      2011 Final Research Report
    • 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

    • NAID

      120005761658

    • Related Report
      2011 Final Research Report
  • [Journal Article] Paracrine Factors of Multipotent Stromal Cells Ameliorate Lung Injury in an Elastase-induced Emphysema Model2011

    • Author(s)
      Ahmad Katsha, Shinya Ohkouchi, Toshihiro Nukiwa, Yasuo Saijo
    • Journal Title

      Molecular Therapy

      Volume: 19 Issue: 1 Pages: 196-203

    • DOI

      10.1038/mt.2010.192

    • Related Report
      2011 Annual Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stanniocalcin-1 from Marrow Stromal Cells (MSC) Rescues Injured Lung Cancer Epithelial Cells by Upregulation of Uncoupling Protein 22011

    • Author(s)
      Shinya Ohkouchi, Gregory Block, Prockop Darwin, Toshihiro Nukiwa
    • Journal Title

      Proceedings of the National Academy of Science of the United States of America (PNAS)

      Volume: (In Press)(未定)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1.2009

    • Author(s)
      Gregory Block, Shinya Ohkouchi, Darwin Prockop Double first
    • Journal Title

      Stem Cells 27

      Pages: 670-81

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [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
    • Related Report
      2011 Final Research Report
  • [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
      日本癌学会総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2011-10-05
    • Related Report
      2011 Annual Research Report
  • [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
    • Related Report
      2011 Final Research Report
  • [Presentation] Novel functions of stanniocalcin-1 (STC1) through Uncoupling Protein 2 (UCP2) upregulation ; 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
      2011欧州呼吸器学会年次総会
    • Place of Presentation
      アムステルダム、オランダ
    • Year and Date
      2011-09-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] Multipotent Stromal Cell-Derived Stanniocalcin-1 Reduces Reactive Oxygen Species and Promotes Survival of Injured A549 Lung Epithelial Cancer Cells through Upregulation of Uncoupling-Protein 2 and Induction of the Warburg Effect2010

    • Author(s)
      S.Ohkouchi, G.J.Block, D.J.Prockop, T.Nukiwa
    • Organizer
      European Respiratory Society Annual Congress 2011
    • Place of Presentation
      Bazcelona, Spain
    • Year and Date
      2010-09-21
    • Related Report
      2010 Annual Research Report
  • [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
    • Related Report
      2011 Final Research Report
  • [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
      第50回日本呼吸器学会総会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2010-04-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] STANNIOCALCIN-1(STC1)DERIVED FROM BONE MULTIPOTENT STROM AL CELLS(MSCS)INHIBIT LUNG EPITHELIAL APOPTOSIS UNDER HYPO XIA AND LACTIC ACIDOSIS(MIMIC ISCHEMIA CONDITION).2009

    • Author(s)
      Shinya Ohkouchi, Toshihiro Nukiwa
    • Organizer
      14^<th> congress Asion Pacific Society of Respirology
    • Place of Presentation
      Seaul, Korea
    • Year and Date
      2009-11-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] Multipotent stromal cells(MSCs)secrete stanniocalcin-1(STC-1)and inhibit lung cancer cell death caused by ischemia.2009

    • Author(s)
      Ohkouchi S, Nukiwa T
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report
  • [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
    • Related Report
      2011 Final Research Report
  • [Book] 肺気腫モデル2011

    • Author(s)
      大河内眞也
    • Publisher
      羊土社
    • Related Report
      2011 Final Research Report
  • [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
    • Publisher
      ライフサイエンス出版
    • Related Report
      2011 Final Research Report
  • [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
    • Related Report
      2011 Final Research Report
  • [Book] マウスラット疾患モデル活用ハンドブック2010

    • Author(s)
      大河内眞也(分担執筆)
    • Publisher
      羊土社
    • Related Report
      2010 Annual Research Report
  • [Book] 特発性間質性肺炎2009

    • Author(s)
      大河内眞也
    • Publisher
      総合医学社
    • Related Report
      2011 Final Research Report
  • [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
    • Filing Date
      2011-01-12
    • Related Report
      2011 Final Research Report
  • [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
    • Filing Date
      2011-02-10
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] (仮)Stanniocalcin-1を用いたケトーシスの治療について2011

    • Inventor(s)
      大河内眞也
    • Industrial Property Rights Holder
      国立大学法人東北大学
    • Filing Date
      2011-01-12
    • Related Report
      2010 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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