Bone marrow-derived mononuclear cell therapy attenuates silica-induced lung fibrosis

Abstract

This study tests the hypothesis that bone marrow-derived mononuclear cell (BMDMC) therapy may reduce lung inflammation and fibrosis leading to an improvement in respiratory mechanics in a murine model of silicosis. 52 female C57BL/6 mice were randomly assigned into four groups. In the silica group (SIL), silica suspension (20 mg/50 μL in saline) was intratracheally instilled. In the control animals, 50 μL saline was administered intratracheally. At 1 h, the control and SIL groups were further randomised, receiving BMDMC (2×10⁶ i.v. control-cell and SIL-cell) or saline (50 μL i.v. control and SIL). BMDMC were obtained from male donor mice. At day 15, lung mechanics, histology, and the presence of Y chromosome, interleukin (IL)-1β, IL-1α, IL-1 receptor antagonist (IL-1RN), IL-1 receptor type 1, transforming growth factor (TGF)-β and caspase-3 mRNA expressions in lung tissue were analysed. In the SIL-cell group, the fraction area of granuloma, the number of macrophages and the collagen fibre content were reduced, yielding improved lung mechanics. The presence of male donor cells in lung tissue was not confirmed using detection of Y chromosome DNA. Nevertheless, caspase-3, IL-1β, IL-1α, IL-1RN and TGF-β mRNA expression diminished after cell therapy. In conclusion, BMDMC acted on inflammatory and fibrogenic processes improving lung function through paracrine effects.