2019 Fiscal Year Final Research Report
Attempt to regenerate skin appendages using reconstituted embryonal-like skin equivalent using human induced pluripotent stem cells
| Project/Area Number |
16H05370
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kyorin University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | ヒト皮膚再生 / ヒトiPS細胞 / 付属器再生 / 毛包 / 分化誘導 |
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| 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.
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| Free Research Field |
皮膚科学 再生医学
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| 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。
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