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

Onishi, Reizo; Ohnishi, Shunsuke; Higashi, Ryosuke; Watari, Michiko; Yamahara, Kenichi; Okubo, Naoto; Nakagawa, Koji; Katsurada, Takehiko; Suda, Goki; Natsuizaka, Mitsuteru; Takeda, Hiroshi; Sakamoto, Naoya

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

Onishi, Reizo; Ohnishi, Shunsuke; Higashi, Ryosuke et al.

Cell transplantation, 2015, 24(12), 2601-2614

Permalink : https://hdl.handle.net/2115/60537

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アクセス権	open access
URI	https://hdl.handle.net/2115/60537
タイトル	Human Amnion-Derived Mesenchymal Stem Cell Transplantation Ameliorates Dextran Sulfate Sodium-Induced Severe Colitis in Rats
著者	Onishi, Reizo ; Ohnishi, Shunsuke ; Higashi, Ryosuke ; Watari, Michiko ; Yamahara, Kenichi ; Okubo, Naoto ; Nakagawa, Koji ; Katsurada, Takehiko ; Suda, Goki ; Natsuizaka, Mitsuteru ; Takeda, Hiroshi ; Sakamoto, Naoya
著者名 Onishi, Reizo
e-Rad_Researcher 10443475 著者名 Ohnishi, Shunsuke
著者名 Higashi, Ryosuke
著者名 Watari, Michiko
e-Rad_Researcher 50450888 著者名 Yamahara, Kenichi
e-Rad_Researcher 00553207 著者名 Okubo, Naoto
e-Rad_Researcher 80360949 著者名 Nakagawa, Koji
著者名 Katsurada, Takehiko
著者名 Suda, Goki
著者名 Natsuizaka, Mitsuteru
e-Rad_Researcher 60261294 著者名 Takeda, Hiroshi
e-Rad_Researcher 10334418 著者名 Sakamoto, Naoya
言語	英語
キーワード	Mesenchymal stem cells (MSCs)
	Amnion
	Colitis
	Macrophages
	NF-κB
発行日	2015-12-18
出版者	Cognizant Communication Corporation
収録物名	Cell transplantation
巻(号)	24(12)
ページ	2601-2614
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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution-NonCommercial 3.0 Unported
PISSN	0963-6897
関連情報	PMID 25812083
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.3727/096368915X687570