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

Respiratory Research

Table 2 Summary of therapeutic benefits of MSC-CM in preclinical animal models

CM Source	Route	Injury Model	Outcomes	Key Factor	Ref.
Mouse BM-MSC	IT	Mouse-ALI/LPS	↓ Neutrophils in BALF ↑ M2 in BALF	IGF-1	[74]
Human BM-MSC	IV	Rat-Pneumonia/E. coli	↑ Survival	LL-37	[81]
Rat BM-MSC	IT	Rat-Lung Injury/I/R	↓ Pro-inflammatory cytokines ↓ Neutrophils in BALF ↑ M2 & Treg in BALF		[82]
Mouse BMC	IN	Mouse-Asthma/OVA	↓ Airway inflammation ↓ Airway hyper-responsiveness ↓ Airway smooth muscle thickness ↑ IL-10 producing Treg & macrophages	APN	[83]
Mouse BM-MSC	IV	Neonatal Mouse-BPD/Hyperoxia	↓ Right ventricular hypertrophy ↓ Intrapulmonary arterioles muscularization ↓ Inflammatory cells & cytokines in BALF Preserve alveoli morphology ↑ Number of BASCs	Opn Csf1	[71, 84, 85]
Hyperoxia Preconditioned Rat BM-MSC	IP	Neonatal Rat- BPD/Hyperoxia	↓ PAH ↓ Right ventricular hypertrophy ↓ Pulmonary artery medial wall thickness Improved lung structure	STC-1	[87]
Rat BM-MSC	IT	Rat-Lung Fibrosis/ Bleomycin	↓ Lung fibrosis ↓ AEC apoptosis		[76]
Rat BM-MSC	IV	Rat-COPD/ cigarette smoke	↓ Lung emphysema ↓ Pulmonary artery medial wall thickness ↑ Number of small pulmonary vessels Protect lung fibroblasts		[91, 92]

AEC – alveolar epithelial cell, ALI – acute lung injury, APN – adiponectin, BALF – bronchoalveolar lavage fluid, BASCs – bronchoalveolar stem cells, BM-MSC – bone marrow-derived mesenchymal stem cells, BPD – bronchopulmonary dysplasia, COPD – chronic obstructive pulmonary disease, Csf1 – macrophage colony stimulating factor 1 (M-CSF), E. coli – Escherichia coli, IN – intranasal, IP – intraperitoneally, I/R – ischemia reperfusion, IT – intratracheal, IV – intravenous, LPS – lipopolysaccharide, M2 – macrophage type 2, Opn – osteopontin, OVA – ovalbumin, PAH – pulmonary artery hypertension, STC-1 – stanniocalcin 1, Treg – regulatory T lymphocyte

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