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Human Amnion-Derived Mesenchymal Stem Cell Transplantation Ameliorates Dextran Sulfate Sodium-Induced Severe Colitis in Rats

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タイトル: Human Amnion-Derived Mesenchymal Stem Cell Transplantation Ameliorates Dextran Sulfate Sodium-Induced Severe Colitis in Rats
著者: Onishi, Reizo 著作を一覧する
Ohnishi, Shunsuke 著作を一覧する
Higashi, Ryosuke 著作を一覧する
Watari, Michiko 著作を一覧する
Yamahara, Kenichi 著作を一覧する
Okubo, Naoto 著作を一覧する
Nakagawa, Koji 著作を一覧する
Katsurada, Takehiko 著作を一覧する
Suda, Goki 著作を一覧する
Natsuizaka, Mitsuteru 著作を一覧する
Takeda, Hiroshi 著作を一覧する
Sakamoto, Naoya 著作を一覧する
キーワード: Mesenchymal stem cells (MSCs)
Amnion
Colitis
Macrophages
NF-κB
発行日: 2015年12月18日
出版者: Cognizant Communication Corporation
誌名: Cell transplantation
巻: 24
号: 12
開始ページ: 2601
終了ページ: 2614
出版社 DOI: 10.3727/096368915X687570
PMID: 25812083
抄録: Mesenchymal stem cells (MSCs) are a valuable cell source in regenerative medicine. Recently, several studies have shown that MSCs can be easily isolated from human amnion. In this study, we investigated the therapeutic effect of human amnion-derived MSCs (AMSCs) in rats with severe colitis. Colitis was induced by the administration of 8% dextran sulfate sodium (DSS) from day 0 to day 5, and AMSCs (1 x 10(6) cells) were transplanted intravenously on day 1. Rats were sacrificed on day 5, and the colon length and histological colitis score were evaluated. The extent of inflammation was evaluated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. The effect of AMSCs on the inflammatory signals was investigated in vitro. AMSC transplantation significantly ameliorated the disease activity index score, weight loss, colon shortening, and the histological colitis score. mRNA expression levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and migration inhibitory factor (MIF) were significantly decreased in the rectums of AMSC-treated rats. In addition, the infiltration of monocytes/macrophages was significantly decreased in AMSC-treated rats. In vitro experiments demonstrated that activation of proinflammatory signals induced by TNF-alpha or lipopolysaccharide (LPS) in immortalized murine macrophage cells (RAW264.7) was significantly attenuated by coculturing with AMSCs or by culturing with a conditioned medium obtained from AMSCs. Although the phosphorylation of I kappa B induced by TNF-alpha or LPS was not inhibited by the conditioned medium, nuclear translocation of NF-kappa B was significantly inhibited by the conditioned medium. Taken together, AMSC transplantation provided significant improvement in rats with severe colitis, possibly through the inhibition of monocyte/macrophage activity and through inhibition of NF-kappa B activation. AMSCs could be considered as a new cell source for the treatment of severe colitis.
資料タイプ: article
URI: http://hdl.handle.net/2115/60537
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 大西 俊介

 

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