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Table 3 Summary of therapeutic benefits of MSC-EVs in preclinical animal models

From: Therapeutic potential of products derived from mesenchymal stem/stromal cells in pulmonary disease

EV Source Route Injury Model Outcomes Key Factor Ref.
Human BM-MSC IT, IV Mouse-ALI/LPS ↓ Lung edema
↓ WBCs & neutrophils in BALF
↓ Total protein & MIP-2 in BALF
↑ KGF in BALF
KGF mRNA [22]
Normoxia & Anoxia pretreated Human BM-MSC IV Mouse-ALI/LPS ↓ WBCs & neutrophils in BALF
↓ Total protein & MIP-2 in BALF
  [94]
Untreated & Poly (I:C)–pretreated Human BM-MSC IT, IV Mouse-Pneumonia/E. coli ↓ Lung injury
↓ WBCs & neutrophils in BALF
↓ Total protein & MIP-2 in BALF
↓ E. coli count in BALF, lung, & blood
↑ Survival
↑ KGF in BALF
KGF mRNA
& CD44
[95]
Human BM-MSC EV-treated AM/IN Mouse-ALI/LPS ↓ Neutrophils in BALF
↓ Total protein & TNF-α in BALF
Mitochondria transfer [96]
Human BM-MSC IV Mouse-Shock/Hemorrhage ↓ Vascular permeability
↓ RhoA GTPase activity in lung
  [66]
Human WJ-MSC IT Mouse-Lung Injury/I/R ↓ Lung edema
↓ Airway resistance
↓ Pulmonary artery pressure
↓ Neutrophil in lung
↓ Inflammatroy cytokines in BALF
↑ KGF, PGE2, &IL-10 in BALF
  [115]
Swine BM-MSC IT Swine-Influenza/SwIV ↓ Lung lesions
↓ WBCs in lung
↓ Inflammatory cytokines in lung
↓ Virus titer in nasal swap & lung
RNA [101]
Mouse & Human BM-MSC IV Mouse-Asthma/AHE ↓ Airway hyper-responsiveness
↓ WBCs in BALF & lung
↓ Th2/Th17 related cytokines in BALF
  [75]
Mouse BM-MSC IV Mouse-PAH/Hypoxia ↓ Right ventricular systolic pressure
↓ Vascular remodeling
↓ Macrophages & cytokines in lung
↓ STAT-3 in lung
  [20]
Rat BM-MSC IV Rat-PAH/Monocrotaline ↓ Pulmonary artery pressure
↓ Pulmonary vascular remodeling
↓ Right ventricle pressure
↓ Right ventricular hypertrophy
  [98]
Mouse & Human BM-MSC IV Mouse-PAH/ Monocrotaline ↓ Pulmonary vascular remodeling
↓ Right ventricle hypertrophy
miRNAs [99]
Human WJ- & BM-MSC IV Neonatal Mouse-BPD/Hyperoxia ↑ Alveolarization
↑ Lung funcion
↓ Lung fibrosis
↓ PAH
↓ Pulmonary vasular remodeling
↓ Pro-inflammatry genes in macrophages
  [67]
Human UC-MSC IT Neonatal Rat-BPD/Hyperoxia ↑ Alveolarization & angiogenesis
↓ Alveolar epithelial cell death
↓ Macrophages & cytokines in lung
VEGF [100]
Human BM-MSC IV Mouse-Lung Fibrosis/Silica ↓ Size of calcified nodules in lung
↓ Hydroxyproline in lung
↓ Inflammatory cells in BALF
↓ Cytokines in BALF
miRNAs & mitochondria transfer [17]
Human BM-MSC IV Mouse-Lung Fibrosis/Silica ↓ Lung collagen
↓ WBCs in BALF
  [97]
Human ASCs IT Mouse-COPD/ elastase ↓ Lung emphysema
↑ FGF2 in lung
  [116]
  1. AHEAspergillus hyphal extract, ALI – acute lung injury, AM – Alveolar macrophages, ASCs – adipose-derived mesenchymal stem cells, BALF – bronchoalveolar lavage fluid, BM-MSC – bone marrow-derived mesenchymal stem cells, FGF2 – fibroblast growth factor 2, IL-10 – interleukin 10, IN – intranasal, I/R – ischemia reperfusion, IT – intratracheal, IV – intravenous, KGF – keratinocyte growth factor, LPS – lipopolysaccharide, MIP-2 – macrophage inflammatory protein 2, miRNAs – microRNAs, OVA – ovalbumin, PAH – pulmonary artery hypertension, PGE2 – prostaglandin E2, STAT-3 – signal transducer and activator of transcription 3, SwIV – swine influanza virus H1N1, Th – T helper lymphocyte, UC-MSC – umbilical cord blood-MSC, VEGF – vascular endothelial growth factor, WBCs – white blood cells, WJ-MSC – umbilical cord Wharton’s jelly-MSC