2023 Fiscal Year Final Research Report

Development of Novel Islet Transplantation Therapy for Type 1 Diabetes Mellitus Using 3D Vascularized Pancreatic Tissue

Research Project

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Project/Area Number	21K08643
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55010:General surgery and pediatric surgery-related
Research Institution	Osaka University
Principal Investigator	Takaichi Shohei 大阪大学, 大学院医学系研究科, 招へい教員 (30804877)
Co-Investigator(Kenkyū-buntansha)	小林省吾大阪大学, 大学院医学系研究科, 准教授 (30452436) 富丸慶人大阪大学, 大学院医学系研究科, 助教 (70528570)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	膵島移植 / 再生医療 / 1型糖尿病 / 筋芽細胞
Outline of Final Research Achievements	In this study, we have constructed vascularized pancreatic tissues consisting of hiPS beta cells, vascular endothelial cells, and fibroblasts by the LbL method, and have reported the therapeutic efficacy of subcutaneous transplantation of the tissue in a mouse model of type 1 diabetes mellitus. We have also reported the efficacy of myoblast in liver regeneration. To reduce the number of cell types used from a practical clinical perspective, we used myoblast as a stromal cell and examined the efficacy in islet cell transplantation. As a result, co-culture of mouse islet cells and myoblasts enhanced insulin secretion, which might be due to the graft angiogenesis and the involvement of the JAK-STAT pathway in islet cells as a molecular mechanism by comprehensive analysis. Co-transplantation of islet cells and myoblasts under the renal capsule of model mice showed therapeutic effects.
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、これまで報告を行ったLbL法による血管化膵組織の開発を、使用する細胞種の低減を研究目的の一つとし、膵島移植における筋芽細胞の有効性を検討した。in vitro実験では、膵島細胞と筋芽細胞の共培養によりグルコース刺激に応答し、インスリン分泌能の増強を認め、その機序としてグラフト内への血管新生および膵島細胞内のJAK-STAT経路の関与が考えられた。in vivo実験では、膵島細胞と筋芽細胞の1型糖尿病モデルマウスへの腎被膜下への共移植による治療効果を認めた。得られた結果は、筋芽細胞のpotentialのみならず、膵島移植における新たな治療標的開発に応用可能な知見となり得る。