Table 1.

Summary of studies in animal models of IPF with therapeutic MSC-EVs.

Experimental Model	EVs Source	Cargo	Effects	Reference
Radiation-induced lung injury	hP-MSCs	miR-214-3p	Attenuates pulmonary vascular damage, inflammation, and fibrosis.	[68]
Bleomycin-induced IPF	BMSCs	miR-186	Relieves IPF by blocking fibroblasts activation by suppressing SOX4 and DKK1 expression.	[72]
E. coli endotoxin induced ALI	BMSCs	KGF mRNA	Restores lung protein permeability and reduces inflammation.	[71]
IRI-induced ALI	BMSCs	miR-21-5p	Decreases edema, pulmonary dysfunction, M1 polarization of alveolar macrophages, and secretion of the cytokines IL-8, IL-1β, IL-6, IL-17, and TNF-α.	[73]
Hypoxia-induced PH	BMSCs	unknown	Prevents activation of hypoxic signaling, lung inflammation, and PH development through inhibition of hypoxic STAT3 signaling.	[74]
Bleomycin-induced IPF	BMSCs	miR-29b-3p	Attenuates IPF progression by suppressing fibroblasts proliferation, migration, and differentiation through suppression of FZD6 expression.	[75]
LPS-induced ALI	BMSCs	miR-23a-3p y miR-182-5p	Attenuate lung injury, EMT, and fibrosis by inhibiting NF-κB and hedgehog pathways.	[76]
LPS-induced ALI	AD-MSCs	unknown	They reduce inflammation, alveolar septal thickening, alter macrophage phenotypes, reduce levels of the proinflammatory cytokine IL-1β, and increase anti-inflammatory IL-10.	[77]
LPS-induced ALI	AD-MSCs	miR-27a-3p	Alleviates lung injury, inhibits NF-κB activation and promotes M2 polarization of alveolar macrophages.	[78]
Bleomycin-induced IPF	hAECs	unknown	Attenuates inflammation and pulmonary fibrosis.	[79]
Bleomycin-induced IPF	MenSCs	miR-Let-7	Attenuates lung inflammation and fibrosis by regulating ROS, mtDNA damage, and NLRP3 inflammasome activation.	[80]

hP-MSCs = Placenta-derived mesenchymal stem cell; BMSCs = Bone marrow mesenchymal stem cell; AD-MSCs = adipose-derived mesenchymal stem cells; hAECs = Human amnion epithelial cells; MenSCs = Menstrual blood-derived stem cells; IPF = Idiopathic pulmonary fibrosis; ALI = Acute lung injury; LPS = Lipopolysaccharide; IRI = Ischemia/reperfusion injury; PH = Pulmonary hypertension; EMT = Epithelial–mesenchymal transition; ROS = Reactive oxygen species; DKK1 = Dickkopf-1; IL-8 = Interleukin-8; IL-1β = Interleukin-1β; IL-6 = Interleukin-6; IL-17 = Interleukin-17; TNF-α = Tumor necrosis factor alpha; IL-10 = Interleukin-10; STAT3 = signal transducer and activator of transcription 3; FZD6 = Frizzled-6; NF-κB = Nuclear factor kappa B; mtDNA= mitochondrial DNA; NLRP3= NLR family pyrin domain containing 3; SOX4= SRY-box transcription factor 4.