Mesenchymal stromal cells from human umbilical cord prevent the development of lung fibrosis in immunocompetent mice
Open Access
- 1 June 2018
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 13 (6), e0196048
- https://doi.org/10.1371/journal.pone.0196048
Abstract
Lung fibrosis is a severe condition resulting from several interstial lung diseases (ILD) with different etiologies. Current therapy of ILD, especially those associated with connective tissue diseases, is rather limited and new anti-fibrotic strategies are needed. In this study, we investigated the anti-fibrotic activity in vivo of human mesenchymal stromal cells obtained from whole umbilical cord (hUC-MSC). Adult immunocompetent C57B/6 mice (n. = 8 for each experimental condition) were injected intravenously with hUC-MSC (n. = 2.5 x 10(5)) twice, 24 hours and 7 days after endotracheal injection of bleomycin. Upon sacrifice at days 8, 14, 21, collagen content, inflammatory cytokine profile, and hUC-MSC presence in explanted lung tissue were analyzed. Systemic administration of a double dose of hUC-MSC significantly reduced bleomycin-induced lung injury (inflammation and fibrosis) in mice through a selective inhibition of the IL6-IL10-TGF beta axis involving lung M2 macrophages. Only few hUC-MSC were detected from explanted lungs, suggesting a "hit and run" mechanism of action of this cellular therapy. Our data indicate that hUC-MSC possess strong in vivo anti-fibrotic activity in a mouse model resembling an immunocompetent human subject affected by inflammatory ILD, providing proof of concept for ad-hoc clinical trials.Keywords
Funding Information
- Ministero Italiano della Salute (Grant RF-2011-02352331)
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