The Double Face of Exosomes Derived from Mesenchymal Stromal Cells in Fibrotic Lung Diseases: Pathology

Several studies have attempted to clarify the role of exosomes and/or microvesicles derived from mesenchymal stromal cells (MSCs) (collectively indicated as extracellular vesicles: MSCs-EVs) in pulmonary fibrosis. Depending on their origin and on the micro-environmental context, MSCs-EVs may support or attenuate the fibrotic invasion of the lung, a hallmark of all Interstitial Lung Diseases (ILDs). Indeed, EVs have emerged as pivotal intercellular mediators and their potential diagnostic and therapeutic applications have been suggested. We aim here to elucidate the dual role of MSCs-derived exosomes and microvesicles: the contribution to pulmonary fibrosis progression, exerted by the MSCs-EVs originated from resident MSCs, or the potential therapeutic activity of those generated from healthy MSCs. Actually, MCSs-EVs appear as the frontiers of cell-free therapy and nano-medicine research in a great number of pre-clinical studies, but developments are needed to optimize and standardize their isolation, production and delivery. Interestingly, since the respiratory system directly communicates with the external environment, lung treatment could be approached by MSCs-EVs nebulization as a preferential administration route, integrating targeted pulmonary delivery with an enhanced patient’s compliance. Hence MSCs-EVs may contribute to ILD pathogenesis, display a potential as biomarkers, and still hold promise as therapeutic agents to reduce lung fibrosis. However further researches are needed to validate their clinical application.