Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice

• Material Type: 博士論文
• Title: Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice
• Author/Editor: Watanabe, Yusuke
• Publication, Distribution, etc.: 新潟大学
• Publication Date: 2019-03-25
• Publication Date (W3CDTF): 2019-03-25
• Alternative Title: Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice; 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
• Degree grantor/type: 新潟大学
• Date Granted: 2019-03-25
• Date Granted (W3CDTF): 2019-03-25
• Dissertation Number: 甲第4523号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第4523号
• Text Language Code: eng
• Note (General): 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; 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; 新大院博（医）甲第845号; 元資料の権利情報 : 【○!C】2018 The Authors
• Persistent ID (NDL): info:ndljp/pid/11498329; https://dl.ndl.go.jp/pid/11498329
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2020-06-07T00:39:19+09:00
• Date Created (W3CDTF): 2019-09-10
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10191/51306
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp