Development of technology for creating transplantable livers using blastocyst complementation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17561
• 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: Iwate Medical University
• Principal Investigator: Suzuki Yuji 岩手医科大学, 医学部, 特任講師 (00779332)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 臓器再生 / 肝移植 / 肝不全 / 再生医療

Outline of Final Research Achievements

In our study, we utilized Hematopoietically Expressed Homeobox (Hhex) knockout mice. These mice are known to exhibit a phenotype of liver deficiency during the developmental stage. Our experiment involved injecting embryonic stem (ES) cells, which were derived from mice expressing Enhanced Green Fluorescent Protein (EGFP), into the embryos of the knockout mice. We then analyzed these chimeric mouse embryos at 11.5 days post-fertilization.
Our analysis revealed that in the chimeras, which were derived from Hhex homozygous knockout embryos, hepatic bud cells had been replaced by the donor ES cells. Notably, these chimeras exhibited normal development from their embryonic stages through to adulthood.Our study has provided new insights into how the environment necessary for the differentiation of pluripotent stem cells into liver tissue can be controlled by Hhex.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

本研究は、異種胚盤胞補完法によって、大型固形臓器である肝臓を創出し、移植可能であることを証明する初の試みである。胚盤胞補完法による肝臓再生の将来的な展開は、ブタなどの大動物の生体内を使って、ヒトに移植可能なヒト多能性幹細胞由来の肝臓を作製することである。実現するためには、ヒトと臓器サイズが合致する個体での臓器欠損動物の作製、進化的な距離の遠い種間でキメラを作出するための技術開発、医学的ニーズと生命倫理に関する議論など解決すべき課題は多いが、胚盤胞補完法によりヒトに移植可能な肝臓をはじめとする臓器を作製することが実現すれば、ドナー臓器不足という人類が抱える医療問題の一つを解消できる可能性がある。