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Development of novel therapy for lipodystrophy and obesity using human iPS cells

Research Project

Project/Area Number 25461347
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionKyoto University

Principal Investigator

Noguchi Michio  京都大学, 医学研究科, 講師 (00432394)

Co-Investigator(Renkei-kenkyūsha) SAKURAI Hidetoshi  京都大学, iPS細胞研究所, 准教授 (80528745)
TAKAHASHI Kazutoshi  京都大学, iPS細胞研究所, 講師 (80432326)
EBIHARA Ken  自治医科大学, 医学部, 准教授 (70362514)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsヒトiPS細胞 / 脂肪萎縮症 / 肥満症 / 疾患特異的iPS細胞 / 多能性幹細胞 / 脂肪細胞分化
Outline of Final Research Achievements

Human iPS and ES cells have adipogenic potentials in vitro. Matrigel containing adipocyte-like cells derived from human iPS and ES cells was transplanted into the subcutaneous tissue of nude mice for 1-4 weeks. Histological analyses and gene expression analyses revealed the presence of adipocyte-like cells at 1-4 weeks. These cells can survive and maintain the differentiated properties of the adipocytes for at least 4 weeks after the transplantation. Then, iPS cells were generated from 5 patients with congenital generalized lipodystrophy, 2 patients with acquired generalized lipodystrophy and a patient with familial partial lipodystrophy. Among them, iPS cells from lipodystrophic patients with BSCL2 nonsense mutations (BSCL2-iPS cells) exhibited marked reduction of lipid droplet formation after adipogenic differentiation, compared with those from healthy subjects. BSCL2-iPS cells could provide valuable models with which to study the pathophysiology of lipodystrophy.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (22 results)

All 2017 2016 2015 2014 2013

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (15 results) Book (2 results)

  • [Journal Article] Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system.2017

    • Author(s)
      N. Yamada-Goto, Y. Ochi, G. Katsuura, Y. Yamashita, K. Ebihara, M. Noguchi, J. Fujikura, D. Taura, M. Sone, K. Hosoda, P.E. Gottschall, K. Nakao.
    • Journal Title

      Neuropeptides

      Volume: 印刷中 Pages: 10-20

    • DOI

      10.1016/j.npep.2017.04.004

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Impaired adipogenic capacity in induced pluripotent stem cells from lipodystrophic patients with BSCL2 mutations2016

    • Author(s)
      1.E. Mori, J. Fujikura, M. Noguchi, K. Nakao, M. Matsubara, M. Sone, D. Taura, T. Kusakabe, K. Ebihara, T. Tanaka, K. Hosoda, K. Takahashi, I. Asaka, N. Inagaki, K. Nakao
    • Journal Title

      Metablism

      Volume: 65 Issue: 4 Pages: 543-556

    • DOI

      10.1016/j.metabol.2015.12.015

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Leptin restores the insulinotropic effect of exenatide in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet2014

    • Author(s)
      T. Sakai, T. Kusakabe, K. Ebihara, D. Aotani, S. Yamamoto-Kataoka, Z. Mingming, VM. Gumbilai, C. Ebihara, M. Aizawa-Abe, Y. Yamamoto, M. Noguchi, J. Fujikura, K. Hosoda, N. Inagaki, K. Nakao
    • Journal Title

      Am J Physiol Endocrinol Metab.

      Volume: 307 Issue: 8 Pages: 712-719

    • DOI

      10.1152/ajpendo.00272.2014

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] In vitro characterization and engraftment of adipocytes derived from human induced pluripotent stem cells and embryonic stem cells.2013

    • Author(s)
      M. Noguchi, K. Hosoda, E. Mori, M. Nakane, K. Nakao, D. Taura, Y. Yamamoto, T. Kusakabe, M. Sone, H. Sakurai, J. Fujikura, K. Ebihara, K. Nakao
    • Journal Title

      Stem Cells and Development

      Volume: 22(21) Issue: 21 Pages: 2895-2905

    • DOI

      10.1089/scd.2013.0113

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis through dysregulated adipocytokine production2013

    • Author(s)
      S. H. Chew, Y. Okazaki, H. Nagai, N. Misawa, S. Akatsuka, K. Yamashita, L. Jiang, Y. Yamashita, M. Noguchi, K. Hosoda, Y. Sekido, T. Takahashi, S. Toyokuni
    • Journal Title

      Carcinogenesis

      Volume: 35(1) Issue: 1 Pages: 164-172

    • DOI

      10.1093/carcin/bgt267

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 疾患特異的iPS細胞を用いた脂肪萎縮症の病態解明2017

    • Author(s)
      野口倫生 中尾一和
    • Organizer
      第31回日本糖尿病・肥満動物学会年次学術集会
    • Place of Presentation
      はまぎんホール ヴィアマーレ(横浜市)
    • Year and Date
      2017-02-10
    • Related Report
      2016 Annual Research Report
  • [Presentation] セイピンノックアウトラットにおける脂肪萎縮の病態解明2016

    • Author(s)
      野口倫生、日下部徹、泉諒太、中尾一和
    • Organizer
      第37回日本肥満学会
    • Place of Presentation
      東京ファッションタウン(東京都)
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] AGPAT2遺伝子変異による脂肪萎縮症2016

    • Author(s)
      日下部徹、田中智洋、宮澤崇、青谷大介、野口倫生、阿部恵、海老原健、中尾一和
    • Organizer
      第37回日本肥満学会
    • Place of Presentation
      東京ファッションタウン(東京都)
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] ミトコンドリアA3243G変異患者から樹立した疾患特異的iPS細胞の機能解析2016

    • Author(s)
      松原正樹、神田一、今村博臣、井上真由美、野口倫生、細田公則、垣塚彰、中尾一和
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] BSCL2遺伝子異常を有する先天性全身性脂肪萎縮症患者からの疾患特異的iPS細胞樹立と解析2016

    • Author(s)
      森栄作、藤倉純二、中尾一泰、野口倫生、日下部徹、海老原健、田中孝之、浅香勲、細田公則、稲垣暢也、中尾一和
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] ミトコンドリアA3243G変異患者から樹立した疾患特異的iPS細胞の機能解析2016

    • Author(s)
      松原正樹、神田一、今村博臣、井上真由美、野口倫生、細田公則、垣塚彰、中尾一和
    • Organizer
      第89回日本内分泌学会学術総会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] ミトコンドリアA3243G変異患者由来iPS細胞のミトコンドリア機能と応用2016

    • Author(s)
      松原正樹、神田一、今村博臣、井上真由美、野口倫生、細田公則、垣塚彰、中尾一和
    • Organizer
      第53回日本臨床分子医学会学術集会
    • Place of Presentation
      東京国際フォーラム(東京都)
    • Year and Date
      2016-04-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] 先天性脂肪萎縮症患者からの疾患特異的iPS細胞樹立と解析2015

    • Author(s)
      森栄作、藤倉純二、中尾一泰、野口倫生、日下部徹、海老原健、田中孝之、浅香勲、細田公則、稲垣暢也、中尾一和
    • Organizer
      日本肥満学会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 脂肪組織形成におけるSeipinの生理的意義2015

    • Author(s)
      野口倫生、日下部徹、泉諒太、海老原健、中尾一和
    • Organizer
      日本肥満学会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 先天性全身性脂肪萎縮症患者からの疾患特異的iPS細胞樹立と解析2014

    • Author(s)
      森栄作、藤倉純二、中尾一泰、野口倫生、日下部徹、海老原健、田中孝之、浅香勲、細田公則、稲垣暢也、中尾一和
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] 1型糖尿病モデルマウスにおける高レプチン血症の影響2013

    • Author(s)
      内藤雅喜、藤倉純二、野口倫生、冨田努、日下部徹、孫徹、海老原健、細田公則、中尾一和
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒトiPS細胞の脂肪細胞分化 -疾患の病態解明と再生医療実現化に向けて-2013

    • Author(s)
      野口倫生、細田公則、中尾一和
    • Organizer
      第31回内分泌代謝学サマーセミナー
    • Place of Presentation
      大分
    • Related Report
      2013 Research-status Report
  • [Presentation] SRF転写活性化因子MRTF-Aの脂肪組織形成における意義2013

    • Author(s)
      趙晃済、南丈也、桑原宏一郎、日下部徹、野口倫生、酒井建、錦見俊雄、中川靖章、木下秀之、桑原佳宏、山田千夏、柴田純子、山田優子、中尾一泰、上嶋健治、保野慎治、細田公則、小池薫、中尾一和
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 高脂肪食負荷レプチントランスジェニック(LepTg)マウスにおけるレプチン感受性の検討2013

    • Author(s)
      野村英生、孫徹、後藤伸子、勝浦五郎、野口倫生、冨田努、藤倉純二、海老原健、細田公則、中尾一和
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] In Vitro Characterization and Engraftment of Adipocytes Derived from Human Pluripotent Stem Cells2013

    • Author(s)
      M. Noguchi, K. Hosoda, K. Nakao
    • Organizer
      31th Annual Scientific Meeting of The Obesity Society (OBESITY 2013)
    • Place of Presentation
      Atlanta, USA
    • Related Report
      2013 Research-status Report
  • [Book] 遺伝子医学MOOK iPS細胞を用いた難病研究 -臨床病態解明と創薬に向けた研究の最新知見2015

    • Author(s)
      野口倫生 細田公則 中尾一和
    • Total Pages
      4
    • Publisher
      メディカルドゥ
    • Related Report
      2014 Research-status Report
  • [Book] 最新肥満症学 基礎・臨床研究の最前線2014

    • Author(s)
      野口倫生 細田公則
    • Total Pages
      4
    • Publisher
      日本臨床社
    • Related Report
      2014 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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