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Attempt to regenerate skin appendages using reconstituted embryonal-like skin equivalent using human induced pluripotent stem cells

Research Project

Project/Area Number 16H05370
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionKyorin University

Principal Investigator

Ohyama Manabu  杏林大学, 医学部, 教授 (10255424)

Co-Investigator(Kenkyū-buntansha) 高橋 良  杏林大学, 医学部, 講師 (00317091)
佐藤 洋平  杏林大学, 医学部, 助教 (90736307)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2016: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywordsヒト皮膚再生 / ヒトiPS細胞 / 付属器再生 / 毛包 / 分化誘導 / 皮膚再生学 / ヒト付属器再生 / 発生・分化 / 付属器 / iPS細胞
Outline of Final Research Achievements

In this study, we attempted to regenerate skin appendages, represented by the hair follicle (HF), in vitro by exposing three-dimensionally assembled human iPS cell (hiPSC)-derived cell composites to activators of embryonic organogenesis signaling pathways.
Technical hurdles were noted, when conventional sheet-like 3D skin reconstruction approach was adopted. However, by developing a new approach of constructing HF-like structures in collagen gel by embedding hiPSC-derived dermal papilla equivalents and placing cylindrically moulded keratinocytes onto them, the structures recapitulating some biological properties of HF were obtained. Exposure of regenerated HF-like structures to the mixture of organogenesis-associated signaling activators further enhanced HF biomarker expression in regenerated structures in vitro.
These findings suggested the strategy for regenerating functional miniorgans, such as skin appendages, with complicated morphology by the application of hiPSC technology.

Academic Significance and Societal Importance of the Research Achievements

これまでヒト皮膚付属器再生は、専ら毛包を主題に、元の組織由来の細胞を免疫不全マウスの体内環境などにおき細胞の自律的な再構成能力に依存する方法で試みられてきた。そのため、素材の量的制約、再生構造のサイズの限界、異種成分の混入などの問題があった。本研究により、ヒトiPS細胞から形態、機能を再現した小器官を再生する際の技術的問題点の一端が明らかになり、また、今までの皮膚付属器再生の課題の解決につながる可能性のある方法論が示された。さらなる技術改良により脱毛症をはじめとする皮膚付属器疾患の再生医療、また治療薬創成のプラットフォームを提供しうる点、また動物愛護の観点からも意義のあるものと考えられる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (15 results)

All 2020 2019 2018 2017 2016 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 6 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Use of human intra-tissue stem/progenitor cells and induced pluripotent stem cells for hair follicle regeneration2019

    • Author(s)
      Ohyama Manabu
    • Journal Title

      Inflammation and Regeneration

      Volume: 39 Issue: 1 Pages: 4-4

    • DOI

      10.1186/s41232-019-0093-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 皮膚・付属器再生におけるiPS細胞の有用性についてー組織幹細胞・前駆細胞との比較を含めて2020

    • Author(s)
      大山 学
    • Organizer
      第19回日本再生医療学会(本来3/12-14開催を延期5/18-29Web開催)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞由来毛乳頭様構造体を用いたin vitroヒト毛包構造再生の試み2020

    • Author(s)
      福山雅大、塚島明希、君嶋桃子、山﨑好美、岡野栄之、大山 学
    • Organizer
      第19回日本再生医療学会(本来3/12-14開催を延期5/18-29Web開催)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 幹細胞・前駆細胞を用いたヒト毛包再生戦略2019

    • Author(s)
      大山 学
    • Organizer
      第118回日本皮膚科学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Attempts to regenerate human hair follicle structure in vitro by three-dimentionally assembling tissue- and iPS cell-derived cell composites.2019

    • Author(s)
      Fukuyama M, Tsukashima A, Kimishima M, Yamazaki Y, Ohyama M.
    • Organizer
      The 44th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト3次元培養皮膚を用いた毛器官発生シグナル因子が上皮ー間葉系相互作用に与える影響の検討2019

    • Author(s)
      福山雅大、塚島明希、君嶋桃子、山崎好美、大山 学
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 毛包幹細胞の基礎と臨床2018

    • Author(s)
      大山 学
    • Organizer
      第117回日本皮膚科学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 皮膚・付属器の幹細胞と再生の現状2018

    • Author(s)
      大山 学
    • Organizer
      第39回日本炎症・再生医学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 安定した3次元培養皮膚作成のためのフィーダーフリー培養ヒトiPS細胞由来細胞調整法の検討2018

    • Author(s)
      福山雅大、塚島明希、君嶋桃子、山﨑好美、大山 学
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト毛包再生に向けた上皮ー間葉系相互作用を可能にする細胞の作成-Dermal papilla細胞を中心に-2017

    • Author(s)
      大山 学
    • Organizer
      第38回日本炎症・再生医学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Current strategy of using stem/ progenitor cells for the treatment of hair diseases2016

    • Author(s)
      Manabu Ohyama
    • Organizer
      18th Hamchun Dermatology Symposium
    • Place of Presentation
      ソウル、韓国
    • Year and Date
      2016-06-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] Springer Series Advances in Stem Cell Biology “Induced Pluripotent Stem Cells; Novel Concepts” Chapter: Strategies to utilize iPS cells for hair follicle regeneration and the treatment of hair loss disorders2020

    • Author(s)
      Manabu Ohyama (Alex Birbrair ed.)
    • Publisher
      Elsevier (San Diego)
    • ISBN
      9780128222287
    • Related Report
      2019 Annual Research Report
  • [Book] 毛髪科学の新展開(第5章:脱毛症の病態から考える毛包再生医療の適応と課題)2019

    • Author(s)
      大山 学 (監修:岩渕徳郎)
    • Total Pages
      283
    • Publisher
      シーエムシー出版
    • ISBN
      9784781314341
    • Related Report
      2019 Annual Research Report
  • [Remarks] 組織幹細胞、ヒトiPS細胞を用いた皮膚付属器再生技術の確立(杏林大学医学部皮膚科学教室)

    • URL

      https://www.kyorin-u.ac.jp/univ/graduate/medicine/education/departments/dermatology/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 組織幹細胞、ヒトiPS細胞を用いた皮膚付属器再生技術の確立

    • URL

      http://www.kyorin-u.ac.jp/univ/graduate/medicine/education/departments/dermatology/

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report 2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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