Experimental and Molecular Medicine (Jul 2023)

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

  • Basalova Nataliya,
  • Arbatskiy Mikhail,
  • Popov Vladimir,
  • Grigorieva Olga,
  • Vigovskiy Maksim,
  • Zaytsev Ivan,
  • Novoseletskaya Ekaterina,
  • Sagaradze Georgy,
  • Danilova Natalia,
  • Malkov Pavel,
  • Cherniaev Andrey,
  • Samsonova Maria,
  • Karagyaur Maxim,
  • Tolstoluzhinskaya Anastasiya,
  • Dyachkova Uliana,
  • Akopyan Zhanna,
  • Tkachuk Vsevolod,
  • Kalinina Natalia,
  • Efimenko Anastasiya

DOI
https://doi.org/10.1038/s12276-023-01017-w
Journal volume & issue
Vol. 55, no. 7
pp. 1399 – 1412

Abstract

Read online

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.