Therapeutic effect of exogenous bone marrow‑derived mesenchymal stem cell transplantation on silicosis via paracrine mechanisms in rats

Abstract

Silicosis is a well-known occupational disease, characterized by epithelial injury, fibroblast proliferation, expansion of the lung matrix and dyspnea. At present, no effective treatment methods for silicosis have been identified. The present study aimed to investigate the protective potential of exogenous bone marrow-derived mesenchymal stem cell (BMSC) transplantation on experimental silica-induced pulmonary fibrosis in rats and analyze the underlying paracrine mechanisms associated with its therapeutic effects. BMSCs were isolated, cultured and passaged from male Sprague-Dawley (SD) rat bone marrow. Third-generation BMSCs were identified by flow cytometry using FITC staining. Following the successful establishment of the silicosis model, exogenous BMSCs were infused into female adult SD rats via the tail vein. Lungs were evaluated using hematoxylin and eosin (H&E) staining. The expression of interleukin-1 receptor antagonist (IL‑1RA), interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α) protein was detected by immunohistochemistry and western blot analysis. Co-localization of sex determining region Y (SRY) and IL-1RA expression was determined by double-label immunofluorescence. The distribution of transplanted BMSCs was tracked by monitoring the expression of SRY in rats. Treatment with BMSCs was found to protect the lungs against injury and fibrosis by the suppression of upregulated IL-1 and TNF-α protein, via triggering IL-1RA secretion. This mechanism was hypothesized to be mediated by paracrine signaling. These results indicate that the release of IL‑1RA from BMSCs via paracrine mechanisms significantly blocks the production and/or activity of IL-1 and TNF-α. The present study provides an experimental basis for cellular therapy in silicosis.