2021 Fiscal Year Final Research Report
Construction of Functional Three-Dimensional Tissue Grafts Derived from iPS Cells Using a Layer-by-layer Cell-coating Technique
| Project/Area Number |
20K17613
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | 膵島移植 / 皮下移植 / 再生医療 / 交互積層法 / iPS細胞 |
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| Outline of Final Research Achievements |
Subcutaneous transplantation with stem cell-derived β-cells is desirable for establishing regenerative medicine as an alternative to pancreas and islet transplantation for patients with type 1 diabetes. However, poor vascularity in the subcutaneous site is burden for success in the transplantation. We investigated the effect of vascularized human induced pluripotent stem cell-derived β-cell (hiPS β-cell) spheroid tissue constructed three-dimensionally using a layer-by-layer cell-coating technique. The vascularized hiPS β-cell spheroid tissue significantly decreased blood glucose levels in diabetic immunodeficient mice when transplanted subcutaneously. Furthermore, host mouse vessels were observed in the explanted vascularized hiPS β-cell spheroid tissue. This therapeutic effect was suggested due to host angiogenesis in the graft.
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| Free Research Field |
肝胆膵疾患領域における基礎研究
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、iPSC由来膵β細胞を用いて、交互積層法により三次元膵組織を作成し、生体内における機能性について検討を行い、次世代の移植・再生医療への臨床応用を目指すことを本研究の目的とした。本研究では、交互積層法を用いて構築した血管構造を伴う3次元ヒトiPSC由来β細胞スフェロイド組織を、糖尿病化免疫不全マウスに皮下移植を行った。血管構造を伴わない組織の皮下移植との比較により、随時血糖値およびグルコース負荷試験での血糖値の有意な低下を認めた。本結果は、同移植法が、安全な移植部位である皮下への新規移植法の開発に有用であり、1型糖尿病患者に対する再生医療の確立に向け、大きな意義を持つと考えられる。
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