Table 2.

Protective Effects of Extracellular Vesicles in Experimental and Clinical Studies of Acute Lung Injury and Acute Respiratory Distress Syndrome

Cell Origin	Authors (Ref. No.)	EV Source	EV Effect
Leukocyte	Guervilly et al. (36)	BAL and plasma from patients with ARDS	Elevated BAL and plasma leukocyte EVs were associated with increased survival and VFDs.
Neutrophil	Neudecker et al. (41)	BAL and stimulated human ex vivo neutrophils from patients with ARDS	Neutrophil EVs transfer miR-223 to AECs, reducing protein permeability and inflammatory cytokine release in AEC monolayers and murine models of staphylococcal lung injury.
	Eken et al. (39) and Gasser et al. (40)	Human ex vivo neutrophils	Binding to MerTK on macrophages increased secretion of TGF-β and decreased TNF-α and IL-8.
Bone marrow MSCs	Zhu et al. (52) and Tang et al. (62)	Cultured adult human bone marrow MSCs	MSC EV treatment in murine intratracheal LPS lung injury reduced alveolar neutrophil influx, protein permeability, inflammatory cytokines, and pulmonary edema. Effects mediated partly by MSC EV transfer of KGF mRNA to AECs and Ang-1 mRNA to endothelial cells.
	Monsel et al. (53) and Hao et al. (64)	Cultured adult human bone marrow MSCs	MSC EV treatment in murine E. coli lung injury reduced alveolar neutrophil influx, bacterial load, protein permeability, and inflammatory cytokines. Effects mediated partly by MSC EV transfer of miR-145 to macrophages.
	Li et al. (56)	Cultured murine bone marrow MSCs	Prophylactic MSC EV treatment increased survival and reduced pulmonary edema and inflammation in rat traumatic lung injury. Effects mediated partly by EV transfer of miR-124-3p.
	Khatri et al. (54)	Cultured pig bone marrow MSCs	MSC EV treatment in pig influenza-induced lung injury reduced lung injury, alveolar protein permeability, and inflammatory cytokines by reducing viral replication in AECs
	Morrison et al. (58)	Cultured adult human bone marrow MSCs	MSC EVs transfer mitochondria to AMs, inducing a modified M2 phenotype; these AMs then attenuated inflammatory lung injury when administered to intratracheal LPS–injured mice.
	Park et al. (55)	Cultured adult human bone marrow MSCs	MSC EV treatment in an E. coli pneumonia model using ex vivo human lungs increased alveolar fluid clearance and reduced alveolar bacterial load and protein permeability.

Definition of abbreviations: Ang-1 = angiopoetin-1; KGF = keratinocyte growth factor; MerTK = Mer tyrosine kinase; MSC = mesenchymal stromal cell; TGF-β = transforming growth factor-β; VFDs = ventilator-free days.