Table 2.

Therapeutic role of extracellular vesicles in various lung complications

Disease	EV source	EV type	Cargo molecule (s)	Major effects /role	Ref.
COPD	Adipose-derived stem cells	Artificial nano-vesicles	FGF2	Increase in epithelial cell proliferation, inhibition of emphysema and regeneration of damaged lung of mice	[22]
PH	Mesenchymal stromal cell	Exosomes	–	Reduction in vascular remodeling and hypoxic PH, inhibition of pro-proliferative STAT3 signaling in pulmonary arterial endothelial cells	[242]
	Mesenchymal Stem Cells	MVs	–	Reduction in mean pulmonary arterial pressures, right ventricle hypertrophy in monocrotaline-PH rat model	[243]
	Mesenchymal stromal cell	Exosomes	–	Promoted mitochondrial function and TCA cycle in pulmonary artery smooth muscle cells	[244]
	Mesenchymal Stem Cells	Exosomes	miRs-34a, −122, −124, and − 127	Reversed PH in monocrotaline mice model	[126]
	Mesenchymal Stem Cells	EVs	–	Reversal of bone marrow endothelial progenitor cells (EPCs) mediated PAH	[129]
	Endothelial cells	MPs	Endoglin	Improved survival and proliferation of pulmonary endothelial cells	[245]
Asthma	Mesenchymal Stem Cells	Exosomes	–	Promoted proliferation and immune-suppression capacity of T regulatory cells	[246]
	Adipose derived Mesenchymal Stem Cells	EVs	–	Reduced airway remodeling and eosinophil counts in lung tissue and BALF of ovalbumin mice.	[247]
	Mesenchymal stromal cells	EVs	–	Abrogated inflammatory response by increasing IL-10 and reducing Th2 and Th17 associated cytokines in the mice model of asthma	[248]
	Bone marrow derived mast cells	Exosomes	IgE receptors (FcξR1)	Reduced IgE levels and mast cell activation in allergic asthma mouse model	[172]
	Human bone marrow derived mesenchymal stem cells	EVs	–	Prevent development of airway hyper responsiveness and pulmonary inflammation in response to allergen	[248]
	Pseudomonas aeruginosa	Exosomes	–	Prevention of allergic reactions by increasingTreg and decreasing the Th2 response.	[249]
	Human mesenchymal stromal cells	Small EVs	miR-146a-5p	Reduction in the infiltration of inflammatory cells, Th2 cytokines and airway hyperresponsiveness	[250]
Lung Cancer	Dendritic cell derived exosomes (DEX)	Exosomes	MAGE tumor antigen	Modest stabilization of NSCLC patients in response to DEX immunotherapy	[251]
ALI/ARDS	Mesenchymal Stem Cells	MVs	Keratinocyte Growth Factor mRNA	Reduction in pulmonary edema and influx of inflammatory cells in BAL of E. coli endotoxin –induced ALI mice;	[252]
	Mesenchymal Stem Cells	Exosomes/MVs	Mitochondria/ miRNA	MSC-MVs transfer depolarized mitochondria to macrophages and increase macrophage bioenergetics; MSC-exosomes modulate TLR signaling and cytokine release in macrophages	[253]
	Mesenchymal stromal cells	EVs	Mitochondria	Reduced inflammation and lung injury; enhanced oxidative phosphorylation in macrophages	[254]
	Mesenchymal Stem Cells	EVs	Runx1 p66 and p52	Enhanced junctional integrity of injured endothelial cells and decreased lung pathology	[255]
	Mesenchymal Stem Cells	EVs	–	Modulated cytoskeletal signaling in endothelial cells and attenuated lung vascular permeability	[256]
	Mesenchymal Stem Cells	MVs	–	Increased alveolar fluid clearance and reduced protein permeability and inflammation; increased antimicrobial in ex-vivo perfused human lung model of bacterial pneumonia	[257]
	Umbilical cord mesenchymal stromal cells	Exosomes	Angiopoietin 1 and hepatocyte growth factor	Restoring alveolar fluid clearance and protein permeability of influenza virus infected alveolar epithelial cells	[258]
	Endothelial progenitor cells	Exosomes	miR-126	Enhanced proliferation, migration of endothelial cells by promoting RAF/ERK signaling, ameliorated LPS-induced lung injury	[259]
	Inducible pluripotent stem cells	Exosomes	siRNAs against ICAM-1	Successfully delivered siRNA into HMVECS and inhibited expression of ICAM-1 and neutrophil adhesion	[260]