Acute respiratory distress vs healthy lung environments differently affect mesenchymal stromal cell extracellular vesicle miRNAs

Sara Rolandsson Enes*, Irakli Dzneladze, Thomas Hampton, Samuel Neff, Lori Asarian, Jayita Barua, Tobias Tertel, Bernd Giebel, Nicolas Pereyra, David McKenna, Pingzhao Hu, Erica Acton, Alix Ashare, Kathleen Liu, Anna Krasnodembskaya, Karen English, Bruce Stanton, Patricia Rocco, Michael Matthay, Claudia Dos SantosDaniel Weiss

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The acute respiratory distress syndrome (ARDS) inflammatory environment alters mesenchymal stromal cell (MSC) gene and protein expression but effects on microRNA (miRNA) content of MSC-extracellular vesicle (EVs) remain unknown. To assess this, sequencing analysis of EV-miRNAs prepared from human bone marrow-derived MSCs (hMSCs) exposed ex vivo to bronchoalveolar lavage fluid (BALF) from ARDS patients or healthy volunteers (HV) identified a number of differentially expressed miRNAs. Discriminant, differential expression, and functional enrichment analyses identified 14 miRNAs significantly changed following ARDS versus HV BALF exposure. Network analysis showed 4 (miR-760, miR-3175, miR-885-3p, and miR-766-3p) of the 14 EV-miRNAs formed a regulatory “hub”, suggesting co-targeting of specific gene pathways. In silico prediction identified a number of pathways important in lung injury. Two miRNAs involved in regulation of the cystic fibrosis transmembrane conductance regulator (CFTR), miRNA-145-5p and miRNA-138-5p, were also significantly increased in ARDS BALF-exposed hMSCs EVs. Functionally, EVs from hMSCs exposed to either ARDS or HV BALF had differential effects on CFTR Cl- secretion by cultured primary human bronchial epithelial cells, an effect predicted to reduce mucociliary clearance. The potential clinical impact of these finding highlights the need for further studies assessing the role of hMSC-EV miRNAs in regulating lung inflammation and mucociliary clearance.
Original languageEnglish
JournalCytotherapy
Early online date20 Jan 2025
DOIs
Publication statusEarly online date - 20 Jan 2025

Keywords

  • Acute respiratory distress
  • healthy lung environments
  • mesenchymal stromal cell
  • miRNAs

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