2019 Fiscal Year Final Research Report

The development of liver regeneration therapy with higher therapeutic effects on liver cirrhosis using a middle-large size liver cirrhosis model.

Research Project

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Project/Area Number	17H04162
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Gastroenterology
Research Institution	Yamaguchi University
Principal Investigator	SAKAIDA Isao 山口大学, 大学院医学系研究科, 教授 (80263763)
Co-Investigator(Kenkyū-buntansha)	藤澤浩一山口大学, 大学院医学系研究科, 助教 (00448284) 高見太郎山口大学, 大学院医学系研究科, 講師 (60511251) 松本俊彦山口大学, 大学院医学系研究科, 助教 (70634723) 山本直樹山口大学, 大学教育機構, 准教授 (90448283)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	肝硬変症 / 再生療法 / 間葉系幹細胞
Outline of Final Research Achievements	To develop liver regeneration therapy with higher therapeutic effects using cultured autologous bone marrow derived mesenchymal stem cells (BM-MSCs) on decompensated liver cirrhosis, we have been conducting translational research. In this study, we have revealed follows; 1) the hepatic arterial infusion of cryopreserved cultured autologous BM-MSCs have equivalent effects on liver cirrhosis model, 2) although BM-MSCs have an immunosuppressive effect, the frequent infusion of cultured autologous BM-MSCs did not accelerate the early stages of hepatocarcinogenesis in highly oncogenic liver cirrhotic murine model, 3) using luciferase-positive BM-MSCs, direct infusion into the liver via portal vein was more effective than peripheral intravenous infusion, 4) the infusion of BM-MSCs showed effects on liver fibrosis and steatosis in a modified murine non-alcoholic steatohepatitis (NASH) model. Therefore, we will develop the next liver regeneration therapy based on these findings.
Free Research Field	肝臓病学
Academic Significance and Societal Importance of the Research Achievements	これまで非代償性肝硬変に対する抗線維化や再生療法の開発が多く実施されているが、肝移植が根治療法であることに変わりはない。これまで我々は「培養自己骨髄間葉系幹細胞を用いた低侵襲肝臓再生療法」を開発し、安全性評価目的の臨床研究を実施している。今回の研究成果は、より治療効果を高めた肝臓再生療法の開発につながることから、肝硬変治療の実現に寄与するだけでなく、他の臓器線維症にも波及効果がある。