Construction of three-dimensional vascularized pancreatic tissue using layer-by-layer method

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18025
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Osaka University
• Principal Investigator: Takaichi Shohei 大阪大学, 医学部附属病院, 医員 (30804877)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 1型糖尿病 / 膵島移植 / 皮下移植 / iPS細胞

Outline of Final Research Achievements

Subcutaneous transplantation 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.

Free Research Field

肝胆膵疾患領域における基礎研究

Academic Significance and Societal Importance of the Research Achievements

本研究は、交互積層法を用いて、細胞の積層化を可能にする技術を利用して、血管構造を伴う3次元ヒト人工多能性幹細胞由来β細胞スフェロイド組織を構築し、糖尿病化免疫不全マウスに同組織の皮下移植を行い、血管構造を伴わない組織の皮下移植マウスに比較し、随時血糖値およびグルコース負荷試験での血糖値が有意に低下したことを報告している。本研究は、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。