Therapeutic effects of adipose-tissue-derived mesenchymal stromal cells and their extracellular vesicles in experimental silicosis

Abstract

BackgroundSilicosis is an occupational disease that affects workers who inhale silica particles, leading to extensive lung fibrosis and ultimately causing respiratory failure. Mesenchymal stromal cells (MSCs) have been shown to exert therapeutic effects in lung diseases and represent an alternative treatment for silicosis. Recently, it has been suggested that similar effects can be achieved by the therapeutic use of extracellular vesicles (EVs) obtained from MSCs. The aim of this study was to investigate the effects of adipose-tissue-derived MSCs (AD-MSCs) or their EVs in a model of silicosis.MethodsSilicosis was induced by intratracheal instillation of silica in C57BL/6 mice. After the onset of disease, animals received saline, AD-MSCs, or EVs, intratracheally.ResultsAt day 30, AD-MSCs and EVs led to a reduction in collagen fiber content, size of granuloma, and in the number of macrophages inside granuloma and in the alveolar septa. In addition, the expression levels of interleukin 1β and transforming growth factor beta in the lungs were decreased. Higher dose of EVs also reduced lung static elastance when compared with the untreated silicosis group.ConclusionsBoth AD-MSCs and EVs, locally delivered, ameliorated fibrosis and inflammation, but dose-enhanced EVs yielded better therapeutic outcomes in this model of silicosis.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0802-3) contains supplementary material, which is available to authorized users.

Clinical Application of Mesenchymal Stem Cell-Derived Extracellular Vesicle-Based Therapeutics for Inflammatory Lung Diseases

“…In addition, these vesicles are engulfed and reutilized by macrophages and MSCs simultaneously shed miRNA-containing exosomes that inhibit macrophage activation by suppressing Toll-like receptor signaling (MyD88-dependent), thereby desensitizing macrophages to the ingested mitochondria [ 83 ]. Furthermore, Bandeira et al reported that mouse AD-MSCs and their EVs ameliorated pulmonary fibrosis and inflammation in a late-stage model of silicosis [ 84 ]. Interestingly, EV treatment at the higher concentration yielded outcomes comparable with those observed by MSC treatment in this study, promoting enhanced impacts on lung mechanics and macrophage infiltration [ 84 ].…”

“…Furthermore, Bandeira et al reported that mouse AD-MSCs and their EVs ameliorated pulmonary fibrosis and inflammation in a late-stage model of silicosis [ 84 ]. Interestingly, EV treatment at the higher concentration yielded outcomes comparable with those observed by MSC treatment in this study, promoting enhanced impacts on lung mechanics and macrophage infiltration [ 84 ].…”

Therapeutic Use of Extracellular Vesicles for Acute and Chronic Lung Disease

“…They also demonstrated that the IV injection of MSC-derived EVs in the lung of silica-exposed mice reduced lung inflammation and the fibrotic response. Bandeira and colleagues demonstrated that intratracheal installation of adipose MSC-derived EVs in a silicosis mouse model led to a reduction in collagen deposition, granuloma size, and macrophage influx [51]. Furthermore, they showed a reduction in the expression of Interleukin 1β and transforming growth factor β.…”

Lysosomal protein surface expression discriminates fat- from bone-forming human mesenchymal precursor cells

“…In inflammatory cells, surface CD107a reflects the state of activation ( Janvier and Bonifacino, 2005 ) and has been implicated in cell adhesion ( Kannan et al, 1996 ; Min et al, 2013 ). In separate reports, CD107a has been described in intracellular vesicles in both osteoblasts and adipocytes ( Bandeira et al, 2018 ; Solberg et al, 2015 ), yet beyond this, essentially nothing is known regarding CD107a in mesenchymal stem cell fate or differentiation decisions.…”