Table 5.

Molecular Mechanism of hucMSCs-EVs in Treating Different Diseases in the Respiratory System

HucMSCs-EVs Cargo	Target/Signaling	Conditions/Diseases	Actiona	Reference
None reported	NF-κB	COVID-19	Systemic inflammation↓	[22]
miR-126, miR-30b	None reported	COVID-19	Pulmonary fibrosis↓	[213]
miR-125b	interferon-stimulated genes	COVID-19	Viral replication↓	[214]
angiopoietin-1, HGF	None reported	COVID-19	Alveolar regeneration↑, angiogenesis↑, and cell survival↑, lung repair↑	[214,215]
miR-146a-5p, miR-451	TRAF6, TLR4/NF-κB, MIF-PI3K-AKT	ALI	M2 polarization↑	[217–219]
miR-199a-5p	CAV1/NRF2/HO-1	ALI	Oxidative stress↓	[220]
None reported	SLC7A11, GPX4, NRF2	ALI	Lung epithelial cells↑	[221,222]
miR-199b-5p	AFTPH, NF-κB	ALI	Inflammatory response↓	[226]
miR-486-5p	SMAD2, Akt	Radiation-induced lung injury	Fibrosis↓, epithelial regeneration↑	[222]
miR-377-3p	RPTOR	ALI	Autophagy↑	[227]
miR-451	TSC1/mTOR	ALI	Macrophage autophagy↓	[228]
None reported	NF-κB	COPD	Inflammation↓	[233]
None reported	MMP-9, TIMP-1	COPD	Alveolar destruction↓	[233]
miR-146a-5p, miR-10a-5p	VEGF-VEGFR2, AKT, MEK/ERK	COPD	Endothelial apoptosis↓, endothelial proliferation↑, gas exchange↑	[234]
None reported	TRAF1/ NF-κB, PI3K/AKT	Asthma	M2 polarization↑, neutrophil infiltration↓	[235]
miR-146a-5p	None reported	Asthma	IL-13↓, eosinophil recruitment↓	[236]
CAV-1	STAT6	Asthma	Airway epithelial integrity↑	[238]
None reported	TGF-β1/Smad2/3	Asthma	Goblet cell metaplasia↓, subepithelial collagen deposition↓, α-SMA-driven fibrosis↓	[239]
miR-146a-5p	TRAF6, IRAK1, NF-κB/NLRP3	asthma	Inflammation↓, epithelial barrier disruption↓	[240]
miR-148a-3p	Hsp90b1	Silicosis	Collagen synthesis↓, fibroblast activation↓	[241]
let-7i-5p	TGFBR1, TGF-β1/Smad3	Silicosis	ECM deposition↓	[242]
miR-223-3p	PWWP2A/NLRP3	Silicosis	Inflammation↓	[243]
miR-26a-5p	Notch	Silicosis	EMT↓	[244]
TGF-β1 siRNA	Smad2/3, Akt/GSK-3β/β-catenin, MAPK, and NF-κB	Lung cancer	EMT↓, migration↓, invasion↓	[248]
miR-320a	SOX4, Wnt/β-catenin	Lung cancer	Proliferation↓, metastasis↓	[249]
miR-410	PTEN	lung cancer	proliferation↑, apoptosis↓	[247]

Notes: ^a ↑ indicates promotion or upregulation; ↓ indicates inhibition or downregulation.