Abstract

BackgroundSilicosis is a common occupational disease, characterized by silicotic nodules and diffuse pulmonary fibrosis. We demonstrated an anti-fibrotic effect of bone marrow mesenchymal stem cells (BMSCs) in silica-induced lung fibrosis. In the present study, we sought to clarify the homing ability of BMSCs and the specific mechanisms for their effects.Methods and resultsThe biodistribution of BMSCs was identified by near-infrared fluorescence (NIRF) imaging in vivo and in vitro. The results showed that BMSCs labeled with NIR-DiR dyes targeted silica-injured lung tissue, wherein they reached a peak at 6 h post-injection and declined dramatically by day 3. Based on these findings, a second injection of BMSCs was administered 3 days after the first injection. The injected BMSCs migrated to the injured lungs, but did not undergo transformation into specific lung cell types. Interestingly, the injection of BMSC-conditioned medium (BMSCs-CM) significantly attenuated silica-induced pulmonary fibrosis. The collagen deposition and number of nodules were decreased in lung tissues of BMSCs-CM-treated rats. In parallel with these findings, the mRNA levels of collagen I, collagen III, and fibronectin, and the content of transforming growth factor (TGF)-β1 and hydroxyproline were decreased in the BMSCs-CM-treated group compared with the silica group. In addition, alveolar epithelial markers were upregulated by BMSCs-CM treatment.ConclusionsBMSCs migrated to injured areas of the lung after silica instillation and attenuated pulmonary fibrosis. The anti-fibrotic effects of BMSCs were mainly exerted in paracrine manner, rather than through their ability to undergo differentiation.

Highlights

  • Silicosis is a common occupational disease, characterized by silicotic nodules and diffuse pulmonary fibrosis

  • bone marrow mesenchymal stem cells (BMSCs) migrated to injured areas of the lung after silica instillation and attenuated pulmonary fibrosis

  • The anti-fibrotic effects of BMSCs were mainly exerted in paracrine manner, rather than through their ability to undergo differentiation

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Summary

Introduction

Silicosis is a common occupational disease, characterized by silicotic nodules and diffuse pulmonary fibrosis. We demonstrated an anti-fibrotic effect of bone marrow mesenchymal stem cells (BMSCs) in silica-induced lung fibrosis. Silicosis is an important fibrotic pulmonary disease induced by inhalation of crystalline silica dust It is an occupational disease worldwide, and no cure has been established to date [1]. BMSCs did not give rise to alveolar epithelial cells directly when they were co-cultured with rat alveolar epithelial type II (ATII) cells in vitro following silica-induced injury. It remains to be established whether similar findings are detected in silica-injured rat lungs and whether BMSCs are actively recruited to the injured lung.

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