Mesenchymal stromal cells from human umbilical cord prevent the development of lung fibrosis in immunocompetent mice

• Published in: PloS one Vol. 13; no. 6; p. e0196048
• Main Authors: Moroncini, Gianluca, Paolini, Chiara, Orlando, Fiorenza, Capelli, Chiara, Grieco, Antonella, Tonnini, Cecilia, Agarbati, Silvia, Mondini, Eleonora, Saccomanno, Stefania, Goteri, Gaia, Svegliati Baroni, Silvia, Provinciali, Mauro, Introna, Martino, Del Papa, Nicoletta, Gabrielli, Armando
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2018; Public Library of Science (PLoS)
• Subjects: Aging; Biology and Life Sciences; Bleomycin; Bone marrow; Cesarean section; Clinical trials; Collagen; Connective tissue diseases; Connective tissues; Etiology; Fibrosis; Health aspects; Immunocompetence; In vivo methods and tests; Inflammation; Injury prevention; Interleukin 1; Interleukin 10; Interleukin 6; Lung diseases; Lungs; Macrophages; Medical research; Medicine and Health Sciences; Mesenchymal stem cells; Mesenchyme; Mice; Prevention; Pulmonary fibrosis; Rats; Research and Analysis Methods; Stem cells; Stromal cells; Therapy; Transplants & implants; Umbilical cord; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0196048

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 C57BL/6 mice (n. = 8 for each experimental condition) were injected intravenously with hUC-MSC (n. = 2.5 × 105) 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-TGFβ 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.