Development of cell-free liver regeneration therapy with the anticipatory method to culture higher-quality MSCs for liver cirrhosis
Project/Area Number |
17K09428
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Yamaguchi University |
Principal Investigator |
TAKAMI Taro 山口大学, 医学部, 講師 (60511251)
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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)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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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)
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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.
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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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Report
(4 results)
Research Products
(46 results)
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[Journal Article] Liver regeneration therapy through the hepatic artery-infusion of cultured bone marrow cells in a canine liver fibrosis model.2019
Author(s)
Nishimura T, Takami T, Sasaki R, Aibe Y, Matsuda T, Fujisawa K, Matsumoto T, Yamamoto N, Tani K, Taura Y, Sakaida I.
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Journal Title
PLoS One.
Volume: 14(1)
Issue: 1
Pages: 234-244
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] No Muscle Depletion with High Visceral Fat as a Novel Beneficial Biomarker of Sorafenib for Hepatocellular Carcinoma.2018
Author(s)
Saeki I, Yamasaki T, Maeda M, Kawano R, Hisanaga T, Iwamoto T, Matsumoto T, Hidaka I, Ishikawa T, Takami T, Sakaida I.
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Journal Title
Liver Cancer.
Volume: 7(4)
Issue: 4
Pages: 359-371
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Treatment strategies for advanced hepatocellular carcinoma: Sorafenib vs hepatic arterial infusion chemotherapy.2018
Author(s)
Saeki I, Yamasaki T, Maeda M, Hisanaga T, Iwamoto T, Fujisawa K, Matsumoto T, Hidaka I, Marumoto Y, Ishikawa T, Yamamoto N, Suehiro Y, Takami T, Sakaida I.
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Journal Title
World J Hepatol.
Volume: 10(9)
Issue: 9
Pages: 571-584
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Assessment of high-fat-diet-induced fatty liver in medaka.2018
Author(s)
Fujisawa K, Takami T, Fukui Y, Nagatomo T, Saeki I, Matsumoto T, Hidaka I, Yamamoto N, Okamoto T, Furutani-Seiki M, Sakaida I
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Journal Title
Biol Open.
Volume: 7(11)
Pages: 341-347
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Deferasirox, an oral iron chelator, with gemcitabine synergistically inhibits pancreatic cancer cell growth in vitro and in vivo.2018
Author(s)
Shinoda S, Kaino S, Amano S, Harima H, Matsumoto T, Fujisawa K, Takami T, Yamamoto N, Yamasaki T, Sakaida I.
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Journal Title
Oncotarget.
Volume: 9(47)
Issue: 47
Pages: 28434-28444
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Blood free-circulating DNA testing by highly sensitive methylation assay to diagnose colorectal neoplasias.2018
Author(s)
Suehiro Y, Hashimoto S, Higaki S, Fujii I, Suzuki C, Hoshida T, Matsumoto T, Yamaoka Y, Takami T, Sakaida I, Yamasaki T.
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Journal Title
Oncotarget.
Volume: 9(24)
Issue: 24
Pages: 16974-16987
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A canine liver fibrosis model to develop a therapy for liver cirrhosis using cultured bone marrow-derived cells.2017
Author(s)
Matsuda T, Takami T, Sasaki R, Nishimura T, Aibe Y, Paredes BD, Quintanilha LF, Matsumoto T, Ishikawa T, Yamamoto N, Tani K, Terai S, Taura Y, Sakaida I.
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Journal Title
Hepatology Communications
Volume: 1
Issue: 7
Pages: 691-703
DOI
Related Report
Peer Reviewed / Open Access
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