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Table 2 Mesenchymal stem/stromal cell (MSC)-based therapy for common immune-mediated lung disorders (animal studies)

From: Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders

Condition Model Main consequences Ref
COPD Ozone-induced mice Protection against oxidative stress-induced mitochondrial dysfunction and decreasing airway inflammation after AT-MSC injection [118]
ALI/ARDS Influenza virus-induced pig Suppression of influenza virus replication and virus-elicited apoptosis in lung epithelial cells by MSC-extracellular vesicles (EVs) [119]
ALI/ARDS LPS-induced mice Reduced total protein and albumin concentrations in bronchoalveolar lavage fluid (BALF) along with attenuated levels of proinflammatory factors and amended rates of anti-inflammatory factors after BM-MSC injection [120]
ALI/ARDS LPS-induced mice Amelioration of lung function and reduction in alveolar collapse, tissue cellularity, collagen, and elastic fiber content in lung tissue in association with lessening in TNF-α, IL-1β, CXCL1, TGF-β, and VEGF by transplantation of MSCs derived from BM and AT [121]
ALI/ARDS LPS-induced mice Mitigated inflammation, oxidative damage, and reduced release of NETs, leading to the promoted overall survival rate of experimental models after MSC transplantation [122]
ALI/ARDS LPS-induced mice Protection against LPS-induced ALI/ARDS by reduction of serum amyloid A (SAA) levels following administration of exosomes derived from microRNA-30b-3p-overexpressing MSCs [123]
COPD CS-induced rat Reduction of TNF-α, IL-1β, MCP-1, and IL-6 and proteases MMP9 and MMP12 levels and promotion of VEGF, VEGF-R2, and TGF-β1 levels in lung tissue, and plummeting pulmonary cell apoptosis upon MSC transplantation [124]
Emphysema Papain-induced rat Induction of protection against pulmonary emphysema by increasing VEGF-A expression and preventing the apoptosis of lung cells after MSC injection [125]
PF Silica-induced rat Inflammatory response inhibition and reduced caspase-3 protein expression with a promotion in the Bcl-2/Bax ratio in pulmonary cell upon AT-MSC injection [126]
BPD Hyperoxia-induced rat Lung function rescue, inhibition of fibrosis and pulmonary vascular remodeling, and improvement of pulmonary hypertension upon MSC-Exo injection [127]
PF Bleomycin-induced mice Decrease of bleomycin-induced PF by AT-MSC intratracheal injection mediated by targeting miR-199 and caveolin-1 expression and AKT phosphorylation [128]
PF Bleomycin-induced mice Alleviation of PF and promotion of survival rate of experimental models after injection of hypoxia-preconditioned MSCs mediated by HGF upregulation [129]
ALI/ARDS LPS-induced mice Reduction in IL-1β and promotion of IL-10 levels in BALF as well as augmented expression of PCNA and KGF and diminished expression of caspase-3 following menstrual blood-derived stem cell (MenSC) injection [130]
Asthma Ovalbumin-induced mice Amelioration of the airway remodeling and inhibition of fibrosis by targeting TGF-β1/Smad pathway after systemic administration of human induced pluripotent stem cell (iPSC)-MSCs [131]
ALI/ARDS Ventilator-induced rat Reduction in albumin levels and inflammatory cells frequencies in BALF leading to the promoted overall survival of experimental models upon injection of UC-MSCs [132]
PF Paraquat-induced mice Inhibition of TNF-α, IL-1β, IL-6 and IL-10 generation resulted in PF restoration upon MSC administration [133]
PF BLM-induced mice PF amelioration upon inhibition of the IL6-IL10-TGF-β axis involving lung M2 macrophages after UC-MSC systemic injection [134]
Asthma Ovalbumin-induced mice Attenuation of numbers of goblet cells, the thicknesses of smooth muscle layer and collagen density along with inhibition of the expression of TGF-β1, TAK1, and p38MAPK in lung tissue after injection of erythropoietin (EPO) gene modified MSCs [135]
ALI/ARDS Bleomycin-induced rat Promotion of vascular permeability, decrease in the rates of proinflammatory cytokines, and improvement in anti-inflammatory cytokine IL-4 levels caused ALI/ARDS amelioration [136]
Asthma Ovalbumin-induced mice Mitigated IL-4, IL-13, and CCL11 levels and collagen fiber content and promoted IL-10 levels in BALF and improved lung function upon MSC administration [137]
Emphysema CS-induced rat Inhibition of induced emphysema development through differentiation of injected MSCs into type II alveolar epithelial cells and dwindled apoptosis and oxidative stress [138]
Asthma Ovalbumin-induced mice Restoration of asthmatic airway remodeling mediated by inhibition of TGF-β1 induced epithelial-mesenchymal transition upon hUC-MSC administration [139]
ALI/ARDS LPS-induced rat Inhibition of inflammatory response resulted in ALI/ARDS rescue after BM-MSC administration [140]
ALI/ARDS Ventilator-induced rat Decreased total lung water as well as dampened lung inflammation achieved by down regulation of TNF-α and up regulation of IL-10 after BM-MSC injection by intravenous route [141]
ALI/ARDS Ventilator-induced pig Absence of significant difference in lung injury rate in the presence of attenuation in expression levels of proinflammatory cytokine and NF-kB translocation upon UC-MSC administration [142]
ALI/ARDS CS-induced sheep Promoted oxygenation and reduced pulmonary edema following UC-MSC administration [143]
  1. Note: PCNA proliferating cell nuclear antigen, KGF keratinocyte growth factor, TGF-β transforming growth factor-beta, VEGF vascular endothelial growth factor, NETs neutrophil extracellular traps, MCP-1 monocyte chemoattractant protein-1, MMPs matrix metallopeptidases, HGF hepatocyte growth factor, TAK1 transforming growth factor-β-activated kinase-1, COPD chronic obstructive pulmonary disease, ALI/ARDS acute lung injury/acute respiratory distress syndrome, PF pulmonary fibrosis, BPD bronchopulmonary dysplasia, LPS lipopolysaccharide, CS cigarette smoke, AT adipose tissue, BM bone marrow, UC umbilical cord