Mesenchymal stromal cells facilitate resolution of pulmonary fibrosis by miR-29c and miR-129 intercellular transfer

Abstract

To date, pulmonary fibrosis remains an unmet medical need. In this study, we evaluated the potency of mesenchymal stromal cell (MSC) secretome components to prevent pulmonary fibrosis development and facilitate fibrosis resolution. Surprisingly, the intratracheal application of extracellular vesicles (MSC-EVs) or the vesicle-depleted secretome fraction (MSC-SF) was not able to prevent lung fibrosis when applied immediately after the injury caused by bleomycin instillation in mice. However, MSC-EV administration induced the resolution of established pulmonary fibrosis, whereas the vesicle-depleted fraction did not. The application of MSC-EVs caused a decrease in the numbers of myofibroblasts and FAPa ⁺ progenitors without affecting their apoptosis. Such a decrease likely occurred due to their dedifferentiation caused by microRNA (miR) transfer by MSC-EVs. Using a murine model of bleomycin-induced pulmonary fibrosis, we confirmed the contribution of specific miRs (miR-29c and miR-129) to the antifibrotic effect of MSC-EVs. Our study provides novel insights into possible antifibrotic therapy based on the use of the vesicle-enriched fraction of the MSC secretome.

Fibrosis: stem cell–secreted vesicles contain anti-scarring RNA molecules

Tiny regulatory RNAs found within membrane-bound vesicles released by fat-derived stem/stromal cells help to resolve lung scarring in a mouse model of pulmonary fibrosis. Nataliya Basalova from Lomonosov Moscow State University in Russia and coworkers observed that molecules secreted by human adult stem/stromal cells help to reduce lung fibrosis in mice with established disease but do not prevent scarring early in the disease process. The researchers traced the beneficial effects to a specific pair of microRNAs contained within vesicles that the stem cells release into their environment. These microRNAs cause scar-forming cells to return to a more flexible state, leading to healthier lung function. Drugs that take advantage of these healing properties could help treat fibrosis, a feature of many chronic diseases, in the lungs and other organs.