title: Human Amnion-Derived Mesenchymal Stem Cell Transplantation Ameliorates Dextran Sulfate Sodium-Induced Severe Colitis in Rats.
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 × 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)-α, interleukin (IL)-1β, 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-α 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 IκB induced by TNF-α or LPS was not inhibited by the conditioned medium, nuclear translocation of NF-κB 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-κB activation. AMSCs could be considered as a new cell source for the treatment of severe colitis.
authors: Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Reizo
authors: R
authors: Onishi
authors: Shunsuke
authors: S
authors: Ohnishi
authors: Ryosuke
authors: R
authors: Higashi
authors: Michiko
authors: M
authors: Watari
authors: Kenichi
authors: K
authors: Yamahara
authors: Naoto
authors: N
authors: Okubo
authors: Koji
authors: K
authors: Nakagawa
authors: Takehiko
authors: T
authors: Katsurada
authors: Goki
authors: G
authors: Suda
authors: Mitsuteru
authors: M
authors: Natsuizaka
authors: Hiroshi
authors: H
authors: Takeda
authors: Naoya
authors: N
authors: Sakamoto
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis / Q000502:physiology; D000650:Amnion / Q000166:cytology*; D000818:Animals; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003092:Colitis / Q000139:chemically induced / Q000628:therapy*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016264:Dextran Sulfate; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000628:therapy; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000276:immunology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D010011:Osteocytes / Q000166:cytology; D010012:Osteogenesis / Q000502:physiology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D017077:Culture Media, Conditioned; D020672:I-kappa B Proteins; C508585:IL1B protein, human; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human