Mesenchymal stem cells stably transduced with a dominant-negative inhibitor of CCL2 greatly attenuate bleomycin-induced lung damage

Shigeki Saito, Takayuki Nakayama, Naozumi Hashimoto, Yasuhiko Miyata, Kensuke Egashira, Norihiko Nakao, Satoshi Nishiwaki, Minoru Hasegawa, Yoshinori Hasegawa, Tomoki Naoe

    研究成果: Contribution to journalArticle査読

    34 被引用数 (Scopus)

    抄録

    Acute respiratory distress syndrome (ARDS) is a crippling disease with no effective therapy characterized by progressive dyspnea. Mesenchymal stem cells (MSCs) have emerged as a new therapeutic modality for ARDS because MSCs can attenuate inflammation and repair the damaged tissue by differentiating into several cell types. Macrophages participate in the development of ARDS; however, MSCs only weakly modulate macrophage function. The chemokine CCL2 is a potent inducer of macrophage recruitment and activation, and its expression is elevated in patients with ARDS. We established MSCs that are stably transduced by a lentiviral vector expressing 7ND, a dominant-negative inhibitor of CCL2, to enhance the therapeutic function of MSCs. 7ND-MSCs retained the innate properties of MSCs and produced a large amount of 7ND. Many 7ND-MSCs were detected in bleomycin-treated lungs (immunostaining 24 hours after injection), suggesting that MSCs could work as a drug delivery tool. Mice treated with 7ND-MSCs showed significantly milder weight loss, lung injury, collagen content, accumulation of inflammatory cells and inflammatory mediators that were induced by bleomycin, and subsequent survival benefit. No evidence of 7ND-MSCinduced toxicity was observed during or after treatment. Thus, inhibiting the effects of macrophages may greatly enhance the ability of MSCs to effect lung repair in ARDS.

    本文言語英語
    ページ(範囲)1088-1094
    ページ数7
    ジャーナルAmerican Journal of Pathology
    179
    3
    DOI
    出版ステータス出版済み - 9 2011

    All Science Journal Classification (ASJC) codes

    • Pathology and Forensic Medicine

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