| Title: | Human Amnion-Derived Mesenchymal Stem Cell Transplantation Ameliorates Dextran Sulfate Sodium-Induced Severe Colitis in Rats |
| Authors: | Onishi, Reizo Browse this author |
| Ohnishi, Shunsuke Browse this author →KAKEN DB |
| Higashi, Ryosuke Browse this author |
| Watari, Michiko Browse this author |
| Yamahara, Kenichi Browse this author →KAKEN DB |
| Okubo, Naoto Browse this author →KAKEN DB |
| Nakagawa, Koji Browse this author →KAKEN DB |
| Katsurada, Takehiko Browse this author |
| Suda, Goki Browse this author |
| Natsuizaka, Mitsuteru Browse this author |
| Takeda, Hiroshi Browse this author →KAKEN DB |
| Sakamoto, Naoya Browse this author →KAKEN DB |
| Keywords: | Mesenchymal stem cells (MSCs) |
| Amnion |
| Colitis |
| Macrophages |
| NF-κB |
| Issue Date: | 18-Dec-2015 |
| Publisher: | Cognizant Communication Corporation |
| Journal Title: | Cell transplantation |
| Volume: | 24 |
| Issue: | 12 |
| Start Page: | 2601 |
| End Page: | 2614 |
| Publisher DOI: | 10.3727/096368915X687570 |
| PMID: | 25812083 |
| Abstract: | 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. |
| Rights: | http://creativecommons.org/licenses/by-nc/3.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/60537 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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