TY - JOUR
T1 - Acute respiratory distress vs healthy lung environments differently affect mesenchymal stromal cell extracellular vesicle miRNAs
AU - Rolandsson Enes, Sara
AU - Dzneladze, Irakli
AU - Hampton, Thomas
AU - Neff, Samuel
AU - Asarian, Lori
AU - Barua, Jayita
AU - Tertel, Tobias
AU - Giebel, Bernd
AU - Pereyra, Nicolas
AU - McKenna, David
AU - Hu, Pingzhao
AU - Acton, Erica
AU - Ashare, Alix
AU - Liu, Kathleen
AU - Krasnodembskaya, Anna
AU - English, Karen
AU - Stanton, Bruce
AU - Rocco, Patricia
AU - Matthay, Michael
AU - Dos Santos, Claudia
AU - Weiss, Daniel
PY - 2025/1/20
Y1 - 2025/1/20
N2 - 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.
AB - 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.
KW - Acute respiratory distress
KW - healthy lung environments
KW - mesenchymal stromal cell
KW - miRNAs
U2 - 10.1016/j.jcyt.2025.01.006
DO - 10.1016/j.jcyt.2025.01.006
M3 - Article
SN - 1465-3249
JO - Cytotherapy
JF - Cytotherapy
ER -