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

Rolandsson Enes, Sara LU orcid ; Dzneladze, Irakli ; Hampton, Thomas H. ; Neff, Samuel L. ; Asarian, Lori ; Barua, Jayita ; Tertel, Tobias ; Giebel, Bernd ; Pereyra, Nicolas and McKenna, David H. , et al. (2025) In Cytotherapy 27(5). p.581-596
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
acute respiratory distress syndrome, bronchoalveolar lavage fluid, CFTR, exosomes, extracellular vesicles, mesenchymal stromal cells, miRNA
in
Cytotherapy
volume
27
issue
5
pages
16 pages
publisher
Taylor & Francis
external identifiers
  • pmid:39945694
  • scopus:85217627073
ISSN
1465-3249
DOI
10.1016/j.jcyt.2025.01.006
language
English
LU publication?
yes
id
a0431cea-a3a3-407a-bcf3-6cea80bf69b5
date added to LUP
2025-07-04 10:13:10
date last changed
2025-07-07 07:22:26
@article{a0431cea-a3a3-407a-bcf3-6cea80bf69b5,
  abstract     = {{<p>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<sup>-</sup> 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.</p>}},
  author       = {{Rolandsson Enes, Sara and Dzneladze, Irakli and Hampton, Thomas H. and Neff, Samuel L. and Asarian, Lori and Barua, Jayita and Tertel, Tobias and Giebel, Bernd and Pereyra, Nicolas and McKenna, David H. and Hu, Pingzhao and Acton, Erica and Ashare, Alix and Liu, Kathleen D. and Krasnodembskaya, Anna D. and English, Karen and Stanton, Bruce A. and Rocco, Patricia R.M. and Matthay, Michael A. and dos Santos, Claudia C. and Weiss, Daniel J.}},
  issn         = {{1465-3249}},
  keywords     = {{acute respiratory distress syndrome; bronchoalveolar lavage fluid; CFTR; exosomes; extracellular vesicles; mesenchymal stromal cells; miRNA}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{581--596}},
  publisher    = {{Taylor & Francis}},
  series       = {{Cytotherapy}},
  title        = {{Acute respiratory distress vs healthy lung environments differently affect mesenchymal stromal cell extracellular vesicle miRNAs}},
  url          = {{http://dx.doi.org/10.1016/j.jcyt.2025.01.006}},
  doi          = {{10.1016/j.jcyt.2025.01.006}},
  volume       = {{27}},
  year         = {{2025}},
}