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
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
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 / 骨髄細胞 / 肝再生 / 肝硬変 / 肝臓再生 |
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.
|
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。
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