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  1. 0 資料タイプ別
  2. 02 学位論文
  1. 250 大学院医歯学総合研究科(医)
  2. 60 博士学位論文
  3. 10 博士学位論文

Mesenchymal stem cells cultured under hypoxic conditions had a greater therapeutic effect on mice with liver cirrhosis compared to those cultured under normal oxygen conditions

http://hdl.handle.net/10191/00051800
http://hdl.handle.net/10191/00051800
d8732394-ca0f-42d9-87f7-8c0233a09156
名前 / ファイル ライセンス アクション
r1nmk911.pdf 本文 (3.3 MB)
r1nmk911_a.pdf 要旨 (576.7 kB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2020-08-31
タイトル
タイトル Mesenchymal stem cells cultured under hypoxic conditions had a greater therapeutic effect on mice with liver cirrhosis compared to those cultured under normal oxygen conditions
言語
言語 eng
キーワード
主題Scheme Other
主題 Mesenchymal stem cells
キーワード
主題Scheme Other
主題 Hypoxic condition
キーワード
主題Scheme Other
主題 Liver cirrhosis
キーワード
主題Scheme Other
主題 PGE2
キーワード
主題Scheme Other
主題 miR210
資源タイプ
資源 http://purl.org/coar/resource_type/c_46ec
タイプ thesis
その他のタイトル
その他のタイトル 通常酸素条件下よりも低酸素条件下で培養した間葉系幹細胞の方が肝硬変マウスに対してより大きな治療効果を認めた
著者 Kojima, Yuichi

× Kojima, Yuichi

WEKO 178003

Kojima, Yuichi

Search repository
著者別名
識別子 178004
識別子Scheme WEKO
姓名 小島, 雄一
抄録
内容記述タイプ Abstract
内容記述 Background: Mesenchymal stem cells (MSCs) can be easily expanded. They can be acquired from medical waste such as adipose and umbilical cord tissues, are influenced by culturing conditions, and exert anti-inflammatory, antioxidant, anti-fibrotic, and angiogenic effects. We analyzed the multi-directional effects of MSCs cultured under hypoxic conditions and their underlying mechanisms in the treatment of liver cirrhosis in a mouse model. Methods: Human bone marrow-derived MSCs cultured under hypoxic (5% O_2; hypoMSCs) and normoxic (21% O_2; norMSCs) conditions were compared by cap analysis of gene expression (CAGE) with or without serum from liver cirrhosis patients. The therapeutic effects of MSCs, including serum liver enzyme induction, fibrosis regression, and hepatic oxidative stress, were evaluated by injecting 1×10^6, 2×10^5, or4 10^4 MSCs/mouse into the tail veins of mice with carbon tetrachloride (CCl_4) -induced liver cirrhosis. Intravital imaging was performed with a two-photon excitation microscope to confirm the various MSC migration paths to the liver. Results: CAGE analysis revealed that the RNA expression levels of prostaglandin E synthase (Ptges) and miR210 were significantly higher in hypoMSCs than in norMSCs. In vivo analysis revealed that both hypoMSCs and norMSCs reduced serum alanine aminotransferase, oxidative stress, and fibrosis compared to that in control mice in a dose-dependent manner. However, hypoMSCs had stronger therapeutic effects than norMSCs. We confirmed this observation by an in vitro study in which hypoMSCs changed macrophage polarity to an anti-inflammatory phenotype via prostaglandin E2 (PGE2) stimulation. In addition, miR210 reduced the rate of hepatocyte apoptosis. Intravital imaging after MSC administration showed that both cell types were primarily trapped in the lungs. Relatively a fewhypoMSCs and norMSCs migrated to the liver. There were no significant differences in their distributions. Conclusion: The therapeutic effect of hypoMSCs was mediated by PGE2 and miR210 production and was greater than that of norMSCs. Therefore, MSCs can be manipulated to improve their therapeutic efficacy in the treatment of liver cirrhosis and could potentially serve in effective cell therapy. MSCs produce several factors with multidirectional effects and function as “conducting cells” in liver cirrhosis.
内容記述
内容記述タイプ Other
内容記述 Regenerative Therapy. 2019, 11, 269-281.
DOI
識別子タイプ DOI
関連識別子 info:doi/10.1016/j.reth.2019.08.005
権利
権利情報 【○!C】 2019, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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 2020-03-23
学位授与番号
学位授与番号 13101甲第4677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911号
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