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Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice
http://hdl.handle.net/10191/51306
http://hdl.handle.net/10191/513067921d910-f2e9-4dee-97a0-c64715cc534b
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本文 (2.7 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2019-07-09 | |||||
| タイトル | ||||||
| タイトル | Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice | |||||
| タイトル | ||||||
| タイトル | Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_46ec | |||||
| 資源タイプ | thesis | |||||
| その他のタイトル | ||||||
| その他のタイトル | 間葉系幹細胞と誘導型マクロファージはマウスに置いて、相互的に作用して肝線維化を改善する | |||||
| 著者 |
Watanabe, Yusuke
× Watanabe, Yusuke |
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| 著者別名 | ||||||
| 識別子Scheme | WEKO | |||||
| 識別子 | 175136 | |||||
| 姓名 | 渡邉, 雄介 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | We describe a novel therapeutic approach for cirrhosis using mesenchymal stem cells (MSCs) and colony-stimulating factor-1-induced bone marrow-derived macrophages (id-BMMs) and analyze the mechanisms underlying fibrosis improvement and regeneration. Mouse MSCs and id-BMMs were cultured from mouse bone marrow and their interactions analyzed in vitro. MSCs, id-BMMs, and a combination therapy using MSCs and id-BMMs were administered to mice with CCl_4-induced cirrhosis. Fibrosis regression, liver regeneration, and liver-migrating host cells were evaluated. Administered cell behavior was also tracked by intravital imaging. In coculture, MSCs induced switching of id-BMMs toward the M2 phenotype with high phagocytic activity. In vivo, the combination therapy reduced liver fibrosis (associated with increased matrix metalloproteinases expression), increased hepatocyte proliferation (associated with increased hepatocyte growth factor, vascular endothelial growth factor, and oncostatin M in the liver), and reduced blood levels of liver enzymes, more effectively than MSCs or id-BMMs monotherapy. Intravital imaging showed that after combination cell administration, a large number of id-BMMs, which phagocytosed hepatocyte debris and were retained in the liver for more than 7 days, along with a few MSCs, the majority of which were trapped in the lung, migrated to the fibrotic area in the liver. Host macrophages and neutrophils infiltrated after combination therapy and contributed to liver fibrosis regression and promoted regeneration along with administered cells. Indirect effector MSCs and direct effector id-BMMs synergistically improved cirrhosis along with host cells in mice. These studies pave the way for new treatments for cirrhosis. STEM CELLS TRANSLATIONAL MEDICINE 2018;00:1–14 | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 学位の種類: 博士（医学）. 報告番号: 甲第4523号. 学位記番号: 新大院博（医）甲第845号. 学位授与年月日: 平成31年3月25日 | |||||
| 書誌情報 | 発行日 2019-03-25 | |||||
| 出版者 | ||||||
| 出版者 | 新潟大学 | |||||
| 権利 | ||||||
| 権利情報 | 【○!C】2018 The Authors | |||||
| 著者版フラグ | ||||||
| 値 | ETD | |||||
| 学位名 | ||||||
| 学位名 | 博士（医学） | |||||
| 学位授与機関 | ||||||
| 学位授与機関名 | 新潟大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2019-03-25 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 13101甲第4523号 | |||||
| 学位記番号 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 新大院博（医）甲第845号 | |||||
