Development of cell-free liver regeneration therapy with the anticipatory method to culture higher-quality MSCs for liver cirrhosis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09428
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Yamaguchi University
• Principal Investigator: TAKAMI Taro 山口大学, 医学部, 講師 (60511251)
• Co-Investigator(Kenkyū-buntansha): 藤澤 浩一 山口大学, 医学部, 助教 (00448284) ; 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 / 細胞外小胞 / エクソソーム

Outline of Final Research Achievements

Bone marrow derived mesenchymal stem cells (BM-MSCs) are a promising source of cells for regenerative medicine and clinical trials have been widely performed to explore their potential. In this study, we created a conditioned medium with whole BM cells (BM cells-conditioned medium; BMC-CM) to reproduce the BM microenvironment. As a result, BMC-CM suppressed morphological deterioration, proliferative decline, and mitochondrial oxidative phosphorylation activity in cultured BM-MSCs. Furthermore, BMC-CM upregulated TNF-stimulated gene 6 in BM-MSCs and the infusion of cultured BM-MSCs with BMC-CM improved liver fibrosis in rat carbon tetrachloride-induced liver cirrhosis. Thus, our developed method to culture higher-quality BM-MSCs using whole BM-derived factors might contribute to develop the higher therapeutic effects of liver regenerative therapy on liver cirrhosis.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

治療効果と安全性を高めた肝臓再生療法を開発するには「高機能・高品質な骨髄MSC」の新規培養法の開発が必要であったが、今回の研究により、全骨髄細胞の培養上清を活用した新規培養法を開発した。また、この培養法は肝臓再生療法に用いる骨髄MSCの品質を向上させることを確認したため、より治療効果の高い骨髄MSCを用いた再生療法の開発につながる。さらに肝臓以外の線維症に対する治療への応用も可能となる。