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    Human mesenchymal stromal cells exert HGF dependent cytoprotective effects in a human relevant pre-clinical model of COPD


    Kennelly, Helen and Mahon, Bernard P. and English, Karen (2016) Human mesenchymal stromal cells exert HGF dependent cytoprotective effects in a human relevant pre-clinical model of COPD. Scientific Reports, 6 (38207). ISSN 2045-2322

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    Abstract

    Bone-marrow derived mesenchymal stromal cells (MSCs) have potent immunomodulatory and tissue reparative properties, which may be beneficial in the treatment of inflammatory diseases such as COPD. This study examined the mechanisms by which human MSCs protect against elastase induced emphysema. Using a novel human relevant pre-clinical model of emphysema the efficacy of human MSC therapy and optimal cell dose were investigated. Protective effects were examined in the lung through histological examination. Further in vivo experiments examined the reparative abilities of MSCs after tissue damage was established and the role played by soluble factors secreted by MSCs. The mechanism of MSC action was determined in using shRNA gene knockdown. Human MSC therapy and MSC conditioned media exerted significant cytoprotective effects when administered early at the onset of the disease. These protective effects were due to significant anti-inflammatory, anti-fibrotic and antiapoptotic mechanisms, mediated in part through MSC production of hepatocyte growth factor (HGF). When MSC administration was delayed, significant protection of the lung architecture was observed but this was less extensive. MSC cell therapy was more effective than MSC conditioned medium in this emphysema model.

    Item Type: Article
    Keywords: Human mesenchymal stromal cells; HGF dependent cytoprotective; effects; human relevant pre-clinical model; COPD;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 10579
    Identification Number: https://doi.org/10.1038/srep38207
    Depositing User: Karen English
    Date Deposited: 25 Feb 2019 12:02
    Journal or Publication Title: Scientific Reports
    Publisher: Nature Publishing Group
    Refereed: Yes
    URI:

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