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In vitro and in vivo reconstruction of cutaneous stem cell system

Research Project

Project/Area Number 17390314
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionResearch Institute, International Medical Center of Japan

Principal Investigator

OKOCHI Hitoshi  Research Institute, International Medical Center of Japan, Department of Regenerative Medicine, Director (30185235)

Co-Investigator(Kenkyū-buntansha) HAMAZAKI Tatsuo S.  Research Institute, International Medical Center of Japan, Division chief (70228534)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥14,610,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2007: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2006: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2005: ¥5,500,000 (Direct Cost: ¥5,500,000)
Keywordskeratinocytes / dermal papilla cell / hair follicle / stem cell / multipotency
Research Abstract

We studied the outgrowth pattern of keratinocytes forming mono-layer sheet. We hypothesized that keratinocytes should balance the tension one another and we could prove it. After keratinocytes stratified, they stopped migrating and proliferating even if there was enough room for them. We demonstrated that keratinocytes produced unknown inhibitory molecules and secreted them in the culture medium. We performed mRNA analysis by differential display methods, but we have not identified the molecule yet.
We focused on the dermal papilla cells because they are key players of hair follicle development. Recently, multipotent stem cells have been isolated from the skin and designated as skin-derived precursors (SKPs) that are localized in the dermal papilla of hair follicles. We found that CD133, a putative stem cell marker for hematopoietic cell, was expressed in the dermal papilla cells and was a novel cell surface marker for the DP cell. We could isolate the DP cells from embryonic and adult mice skin by using this marker and proved that CD133 positive cells had hair follicle-inducing ability. Moreover CD133 positive cells differentiated neuronal and mesodermal lineage cells. We also succeeded in culturing DP cells for a long time with keeping hair follicle-inducing ability. Furthermore we demonstrated that artificially aggregated DP cells promoted hair follicle induction when they were combined with epidermal cells in vivo. We noticed that when the hair follicle was reconstructed, sebaceous glands were accompanied at the same time. We also confirmed that cultured dermal papilla cells became dermal sheath cells as well as dermal papilla cells in vivo. Our observations imply that dermal papilla cells may rebuild their microenvironment and behave as both dermal papilla cells and dermal sheath cells as they adjust.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (37 results)

All 2008 2007 2006 2005 Other

All Journal Article (18 results) (of which Peer Reviewed: 7 results) Presentation (12 results) Book (4 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Isolation of Murine Hair-Inducing Cells Using the Cell Surface Marker Prominin-1/CD133.2007

    • Author(s)
      Ito Y, Hamazaki TS, Ohnuma K, Tamaki K, Asashima M, Okochi H
    • Journal Title

      J Invest Dermatol 127

      Pages: 1052-60

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Long term culture of mouse vibrissal dermal papilla cells and de novo hair follicle induction2007

    • Author(s)
      Osada A, Iwabuchi T, Kishimoto J, Hamazaki TS, Okochi H
    • Journal Title

      Tissue Eng 13

      Pages: 975-82

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The involvement of Gabl and PI 3-kinase in betal integrin signaling in keratinocytes.2007

    • Author(s)
      Kuwano Y, Fujimoto M, Watanabe R, Ishiura N, Nakashima H, Komine M, Hamazaki TS, Tamaki K, Okochi H
    • Journal Title

      Biochem Biophys Res Commun. 361

      Pages: 224-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Isolation of Murine Hair-Inducing Cells Using the Cell Surface Marker Prominin-1/ CD 133.2007

    • Author(s)
      Ito Y, Hamazaki TS, Ohnuma K, Tamaki K, Asashima M, Okochi H
    • Journal Title

      J Invest Dermatol 127

      Pages: 1052-60

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Long term culture of mouse vibrissal dermal papilla cells and de novo hair follicle Induction2007

    • Author(s)
      Osada A, Iwabuchi T, Kishimoto J, Hamazaki TS, Okochi H
    • Journal Title

      Tissue Eng 13

      Pages: 975-82

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The involvement of Gab 1 and PI 3-kinase in betal integrin signaling in keratinocytes.2007

    • Author(s)
      Kuwano Y, Fujimoto M, Watanabe R, Ishiura N, Nakashima H, Komine M, Hamazaki TS, Tamaki K, Okochi H
    • Journal Title

      Biochem Biophys Res Commun 361

      Pages: 224-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Isolation of Murine Hair-lnducing Cells Using the Cell Surface Marker Prominin-1/CD133.2007

    • Author(s)
      Ito Y, Hamazaki TS, Ohnuma K, Tamaki K, Asashima M, Okochi H
    • Journal Title

      J Invest Dermatol 127

      Pages: 1052-1060

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation of Murine Hair-Inducing Cells Using the Call Surface Marker Prominin-1/CD133.2007

    • Author(s)
      Ito Y, Hamazaki TS, Ohnuma K, Tamaki K, ASahima M, Okochi H
    • Journal Title

      J Invest Dematol 127

      Pages: 1052-60

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Activation of Akt by mechanical stretching in human epidermal keratinocytes.2006

    • Author(s)
      Yano S, Komine M, Fujimoto M, Okochi H, Tamaki K
    • Journal Title

      Exp Dermatol 15

      Pages: 356-61

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 皮膚の幹細胞-最新の知見と再生医療への応用2006

    • Author(s)
      大河内仁志
    • Journal Title

      日皮会誌 116

      Pages: 1739-1744

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 皮膚stem cellによる再生医療2006

    • Author(s)
      大河内仁志
    • Journal Title

      臨床皮膚科 60

      Pages: 163-165

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary 2006 Annual Research Report
  • [Journal Article] Activation of Akt by mechanical stretching in human epidermal keratinocytes.2006

    • Author(s)
      Yano S, Komine M, Fujimoto M, Okochi H, Yamaki K
    • Journal Title

      Exp Dermatol 15

      Pages: 356-61

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 皮膚の肝細胞-最新の知見と再生医療への応用2006

    • Author(s)
      大河内仁志
    • Journal Title

      日皮会誌 116

      Pages: 1739-1744

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Characterization and localization of side population cells in mouse skin2005

    • Author(s)
      Yano S, Ito Y, Fujimoto M, Hamazaki TS, Tamaki K, Okochi H
    • Journal Title

      Stem Cells 23

      Pages: 834-841

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary 2005 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term culture of adult murine epidermal keratinocytes2005

    • Author(s)
      Yano s, Okochi H
    • Journal Title

      Br J Dermatol 153

      Pages: 1101-1104

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 皮膚再生と幹細胞2005

    • Author(s)
      大河内仁志
    • Journal Title

      総合臨床 54

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Long-term culture of adult murine epidermal keratinocytes2005

    • Author(s)
      Yano S, Okochi H
    • Journal Title

      Br J Dermatol 153

      Pages: 1101-1104

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Long term culture of mouse vibrissal demal papilla cells and de novo hair follicle induction

    • Author(s)
      Osada A, Iwabuchi T, Kishimoto J, Hamazaki TS, Okochi H
    • Journal Title

      tissue Eng (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Presentation] The hair-inducing clonal cell lines from dermal papilla and dermal sheath cells of mouse vibrissa follicles.2007

    • Author(s)
      Osada A, Kobayashi K, Masui S, Hamazaki TS, Okochi H
    • Organizer
      5^<th> International Congress of Hair Research
    • Place of Presentation
      カナダ、バンクーバー
    • Year and Date
      2007-06-14
    • Related Report
      2007 Annual Research Report
  • [Presentation] マウス毛包内CD133陽性細胞の分化多能性の検討2007

    • Author(s)
      伊藤 ゆり子, 浜崎 辰夫、大沼 清、玉置 邦彦、浅島 誠、大河内 仁志
    • Organizer
      第32回日本研究皮膚科学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-04-19
    • Related Report
      2007 Annual Research Report
  • [Presentation] The hair-inducing clonal cell lines from dermal papilla and dermal sheath cells of mouse vibrissa follicles2007

    • Author(s)
      Osada A, Kobayashi K, Masui S, Hamazaki TS, Okochi H
    • Organizer
      5^<th> International Congress of Hair Research
    • Place of Presentation
      Vancouver, Canada
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] マウス毛包内CD133陽性細胞の分化多能性の検討2007

    • Author(s)
      伊藤ゆり子 浜崎辰夫, 大沼清, 玉置邦彦, 浅島誠, 大河内仁志
    • Organizer
      第32回日本研究皮膚科学会
    • Place of Presentation
      横浜、神奈川県
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A new surface marker for dermal papilla cells2006

    • Author(s)
      Ito Y, Hamazaki TS, Tamaki K, Asashima M, Okochi H
    • Organizer
      67^<th> Annual meeting of the Society of Investigative Dermatology
    • Place of Presentation
      Philadelphia, Pennsylvania, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Long term culture of mouse vibrissal dermal papilla cells and de novo hair follicle induction2006

    • Author(s)
      Osada A, Iwabuchi T, Kishimoto J, Hamazaki TS, Okochi H
    • Organizer
      Europian Hair research Society Annual Meeting 2006
    • Place of Presentation
      London, United Kingdom
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 新規毛乳頭細胞表面マーカーの同定と発毛誘導能の検討2006

    • Author(s)
      伊藤ゆり子, 浜崎辰夫, 玉置邦彦, 浅島誠, 大河内仁志
    • Organizer
      日本研究皮膚科学会 第31回年次学術大会
    • Place of Presentation
      京都
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 毛包誘導能を有する毛乳頭細胞の長期継代培養と毛包誘導能の検討2006

    • Author(s)
      長田亜樹, 岩渕徳郎, 岸本治郎, 浜崎辰夫, 大河内仁志
    • Organizer
      日本研究皮膚科学会 第31回年次学術大会
    • Place of Presentation
      京都
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A new surface marker for dermal papilla cells.2006

    • Author(s)
      Ito Y, Hamazaki TS, Tamaki K, Asashima M, Okochi H
    • Organizer
      67^<th> Annual meeting of the Society of Investigative Dermatology
    • Place of Presentation
      Philadelphia, Pennsylvania, USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Long term culture of mouse vibrissal dermal papilla cells and de novo hair follicle Induction.2006

    • Author(s)
      Osada A, Iwabuchi T, Kishimoto J, Hamazaki TS, Okochi H
    • Organizer
      European Hair research Society Annual Meeting
    • Place of Presentation
      London, United Kingdom
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The fate of keratinocyte stem cells in vitro is determined in part by the calcium concentration and physical tension as well as by growth factors2005

    • Author(s)
      Okochi H
    • Organizer
      Epidermal Stem Cells Meeting
    • Place of Presentation
      Winter Park, Colorado, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Skin as a stem cell source2005

    • Author(s)
      Okochi H
    • Organizer
      The annual Dermatological meeting in Taiwan
    • Place of Presentation
      Taichung, Taiwan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 皮膚に存在する多能性幹細胞-最近の進歩『最新皮膚科学大系2008-2009』2008

    • Author(s)
      大河内仁志
    • Total Pages
      325
    • Publisher
      中山書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 表皮由来幹細胞 遺伝子医学MOOK別冊「進みつずける細胞移植治療の実際」2008

    • Author(s)
      大河内仁志
    • Total Pages
      260
    • Publisher
      株式会社メディカルドゥ
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 皮膚に存在する多能性幹細胞-最近の進歩最新皮膚科学大系(2008-2009)2008

    • Author(s)
      大河内 仁志
    • Publisher
      中山書店
    • Related Report
      2007 Annual Research Report
  • [Book] 細胞増殖因子と再生医療2006

    • Author(s)
      大河内仁志, 長田亜樹, 伊藤宗成
    • Total Pages
      401
    • Publisher
      メディカルレビュー社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.imcj.go.jp/rese/top/index.html

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.imcj.go.jp/rese/top/index.html

    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] 毛乳頭細胞培養方法2006

    • Inventor(s)
      大河内仁志, 長田亜樹, 岸本治郎
    • Industrial Property Rights Holder
      大河内仁志, 資生堂
    • Industrial Property Number
      2006-104312
    • Filing Date
      2006-04-05
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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