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Blockade of CD26 Augments the Therapeutic Potential of Marrow Stem Cells in the Liver

フォーマット:
論文(リポジトリ)
責任表示:
Matsuda, Yasunobu ; Wakai, Toshifumi ; Hirose, Yuki ; Sakata, Jun ; Kobayashi, Takashi ; Osawa, Mami ; Fujimaki, Shun ; Kubota, Masayuki
出版情報:
新潟大学医学部保健学科, 2014-03
掲載情報:
新潟大学保健学雑誌 — 新潟大学保健学雑誌
ISSN:
21884617  CiNii Research  Webcat Plus  JAIRO
著者名:
Matsuda, Yasunobu
Wakai, Toshifumi
Hirose, Yuki
Sakata, Jun
Kobayashi, Takashi
Osawa, Mami
Fujimaki, Shun
Kubota, Masayuki
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巻:
11
通号:
1
開始ページ:
39
終了ページ:
49
概要:
Background & Aims: The therapeutic potential of marrow stem cells for liver disease is currently unclear. The aim of this study was to investigate whether potentiating the chemotaxis ability of stromal cell-derived factor 1 could augmen t the engraftment of marrow stem cells and ameliorate tissue damage. Methods: Female mice reconstructed with β-galactosidase-positive male marrow cells were repeatedly injected with carbon tetrachloride to induce liver cirrhosis. The statuses of stromal cell-derived factor 1 and its inhibitor CD26 were examined by immunohistochemical staining, enzyme-linked immunosorbent assays and colorimetric assays. Recipients were treated with an inhibitory peptide for CD26(Diprotin A)together with granulocyte colony-stimulating factor, and the marrow-derived cells were tracked through the β-galactosidase activity or sex-determining region on the Y chromosome. Results: Stromal cell-derived factor 1 expression and CD26 activity were both significantly increased and marrow-derived hepatocytes were not observed in liver cirrhosis, suggesting that the potential of stem cell homing is impaired by liver damage. Granulocyte colony-stimulating factor only induced a few cell clusters comprising 2-6 marrow-derived hepatocytes at a late stage of liver cirrhosis. In contrast, when animals with liver cirrhosis were treated with Diprotin A after granulocyte colonystimulating factor-induced stem cell mobilization, marrow-derived hepatocytes increased to 2-4% of the total hepatocytes and both the serum albumin and hepatic hydroxyproline contents were ameliorated(p < .05). Conclusions: Maintaining the chemotaxis ability of stromal cell-derived factor 1 may represent an effective strategy for validating stem cell therapy. 続きを見る
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