Adipose-Derived Stem Cells Stimulate Reendothelialization in Stented Rat Abdominal Aorta

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  • Sato Tomohiko
    Department of Internal Medicine, Faculty of Medicine, University of Tokyo
  • Takahashi Masao
    Department of Internal Medicine, Faculty of Medicine, University of Tokyo
  • Fujita Daishi
    Department of Internal Medicine, Faculty of Medicine, University of Tokyo
  • Oba Shigeyoshi
    Department of Internal Medicine, Faculty of Medicine, University of Tokyo
  • Nishimatsu Hiroaki
    Department of Urology, Faculty of Medicine, University of Tokyo
  • Nagano Tetsuo
    Graduate School of Pharmaceutical Sciences, University of Tokyo
  • Suzuki Etsu
    St. Marianna University School of Medicine

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Abstract

Background: Although drug-eluting stents (DES) have been widely used for the treatment of coronary artery disease, they potentially increase the risk of late thrombosis. It is, therefore, desirable to establish a strategy to stimulate reendothelialization. Endothelial injury models have been widely used to analyze the mechanisms of coronary restenosis. However, animal models deployed with coronary stents in the blood vessels are necessary to accurately analyze the mechanisms of coronary restenosis and late thrombosis because persistent inflammation occurs around the coronary stents. Methods and Results: Coronary stents were implanted into rat abdominal aorta and adipose tissue-derived stem cells (ASC) were administered from the adventitial side. Reendothelialization was then visualized by Evans blue staining, and neointimal formation was analyzed histologically. ASC significantly stimulated reendothelialization and inhibited neointimal formation in bare metal stents (BMS)-implanted aorta. In addition, ASC promoted reendothelialization in DES-implanted aorta; however, the effects were weaker than in BMS-implanted aorta. Among the cytokines that ASC produce, adrenomedullin (AM) significantly stimulated reendothelialization and inhibited neointimal formation in BMS-implanted aorta, when an adenovirus expressing AM was administered from the adventitial side. Conclusions: These results suggest that ASC produce several cytokines that stimulate reendothelialization and inhibit neointimal formation in stent-deployed vessels, and that AM could mediate these effects.  (Circ J 2014; 78: 1762–1769)<br>

Journal

  • Circulation Journal

    Circulation Journal 78 (7), 1762-1769, 2014

    The Japanese Circulation Society

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