Bile Duct Regeneration for Transplantable Functional Liver Graft

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K19592
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Keio University
• Principal Investigator: Yagi Hiroshi 慶應義塾大学, 医学部(信濃町), 講師 (20327547)
• Co-Investigator(Kenkyū-buntansha): 須藤 亮 慶應義塾大学, 理工学部(矢上), 教授 (20407141) ; 水口 裕之 大阪大学, 薬学研究科, 教授 (50311387)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Keywords: 脱細胞化 / 臓器再生 / 胆管再生 / 肝臓移植

Outline of Final Research Achievements

In this study, we performed implantation of the engineered graft with a large number of human iPS cell derived multiple cell types into the pre-clinical porcine model inducing immune-deficient, by the nation-wide collaboration work. Importantly, the work includes the validation of the production process, the establishment of the safety evaluation criteria for the product by the proteomics analysis as well as the bile duct regeneration. These effective collaborations of medicine and engineering approach will successfully provide the novel technology for large- scale organ reconstruction with bile production and novel therapeutic option for end-stage liver disease.

Free Research Field

移植外科

Academic Significance and Societal Importance of the Research Achievements

本研究はこれまで肝臓再生研究の最大の障壁となっていた「胆汁産生と排泄」機能をもった肝臓を、ヒトiPS細胞とブタ由来の臓器骨格を用いることで実現化しようとする非常に挑戦的な研究である。本研究成果は、世界初の胆汁産生を伴う肝臓再生の実現化はもちろん、今後の臓器再生における極めて斬新な研究ツールへの発展、あるいは体内における肝再生の新たな基礎的知見の創出に繋がり、最終的にヒトiPS細胞を用いた再生肝臓が創出されれば、今後の医療を大きく変える代替臓器開発に大きな布石となり得る。