Effects of extracellular vesicles from mesenchymal stromal cells in experimental silicosis

Mesenchymal stromal cells (MSC) have been shown to yield beneficial effects in a variety of lung diseases. Recently, it has been suggested that similar effects can be achieved by the therapeutic use of extracellular vesicles (EVs) released by these cells. So far, no study has evaluated the use of EVs in experimental silicosis. The aim of this study was to investigate the therapeutic effects of adipose tissue derived MSC (AD-MSC) and EVs produced by these MSC on lung mechanics, histology, inflammation and remodeling in a model of silicosis. Thirty female C57BL/6 mice (18-22 g) received saline or silica (20 mg) intratracheally. At day 15, silica animals received intratracheal instillation of saline, AD-MSC (105 cells), or EVs in two different doses: equivalent to 105 cells (∼15 µg of protein content) or 106 cells (∼150 µg). AD-MSC were obtained from 5 C57BL/6 mice and were characterized by flow cytometry and differentiation induction. EVs were obtained through ultracentrifugation of conditioned media. Scanning electron microscopy analysis showed the prevalence of exosomes (diameter: 40-100 nm). The release of extracellular vesicles was observed through transmission electron microscopy. At day 30, AD-MSC and EVs (independent of the dose) led to a reduction in collagen fiber content inside the granuloma and in the alveolar septa. Moreover, AD-MSC and the higher dose of EVs attenuated the number of macrophages and the size of granuloma. However, these beneficial effects did not improve lung mechanics. In conclusion, in the present model of silicosis, AD-MSC and EVs reduced fibrosis, and a higher dose of EVs had a better effect on lung inflammation. Supported by: CAPES, FAPERJ, CNPq.