2021 Fiscal Year Final Research Report

Examination of the therapeutic effect of allogeneic liver organoids on a medium-sized animal liver cirrhosis model

Research Project

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Project/Area Number	19H03733
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Yokohama City University
Principal Investigator	MURATA Soichiro 横浜市立大学, 医学研究科, 客員准教授 (40436275)
Co-Investigator(Kenkyū-buntansha)	田所友美横浜市立大学, 医学部, 助教 (20507644) 谷口英樹東京大学, 医科学研究所, 教授 (70292555)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	オルガノイド / 肝硬変 / 同種 / iPS細胞
Outline of Final Research Achievements	Liver cirrhosis is a terminal image of chronic liver disease that develops due to various causes, and although there is no radical cure other than liver transplantation, there is an overwhelming shortage of donors. The purpose of this study is to establish a safe surgical technique in a cirrhosis model and to investigate the long-term therapeutic effect of allogeneic liver organoids on cirrhosis. We have established a method for inducing differentiation of endoderm cells, mesenchymal cells, and vascular endothelial cells using monkey iPS cells. Furthermore, we established a method for producing monkey iPS cell-derived hepatic organoids from three types of cells that have been induced to differentiate. Furthermore, monkey iPS cell-derived liver organoids were transplanted into a cynomolgus monkey liver cirrhosis model, and the therapeutic effect was examined. As a result, it was suggested that the transplanted individual had an effect of improving fibrosis.
Free Research Field	再生医学
Academic Significance and Societal Importance of the Research Achievements	肝硬変は様々な原因で発症する慢性肝疾患の終末像であり、肝移植以外に根治療法がないが、圧倒的なドナー不足の状態である。したがって、臓器移植に代わる治療法の開発は、多くの患者救済のために必須である。また、臓器不全症に対する待機的治療には莫大なコストを要することから、医療経済学的観点からもその開発ニーズが非常に高まっている。本研究成果により、肝臓オルガノイドを用いて臓器移植を行わずに肝硬変を治療出来ることが示唆され、ドナー不足解消による患者救済及び待機的治療継続によるコストを削減できる可能性が示され、社会的に重要な意義をゆうすると考えられた。