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

Mohammadipoor, Arezoo; Antebi, Ben; Batchinsky, Andriy I.; Cancio, Leopoldo C.

doi:10.1186/s12931-018-0921-x

Respiratory Research

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]

AHE – Aspergillus 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

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