Table 1.
Summary of studies reporting the use of MSCs and/or their products in preventing lung injury.
| Use of Cells or Their Products | Study Model | Effects Due to MSC Treatment | Mechanisms | References |
|---|---|---|---|---|
| BM-MSCs | Mouse lung IRI | Protection against cold IRI in lung transplants | Improved arterial blood oxygenation capacity, reduced levels of pro-inflammatory cytokine and cell apoptosis | [29] |
| MSC-derived EVs | Rat lung IRI and EVLP | Improved tissue integrity and metabolism | Decrease in vascular resistance and rise in perfusate NO metabolites; Up-regulation of genes involved in the resolution of both inflammation and oxidative stress | [34] |
| UC-MSCs and UC-MSC-derived EVs | Mouse lung IRI | Attenuation of lung dysfunction and injury by improving the efficacy of EVLP | Decreased levels of edema, neutrophil infiltration and myeloperoxidase; decrease in pro-inflammatory cytokines and increase in KGF, PGE2 and IL-10; | [35] |
| UC-MSC-derived EVs | E. coli-induced rat lung injury | Increased survival | Enhanced phagocytosis of E. coli | [36] |
| BM-MSCs and BM-MSC-derived CM | Rat lung Injury | Attenuation of lung injury | Reduced levels of pro-inflammatory cytokine | [37] |
| BM-MSCs and BM-MSC-derived CM | Ventilator-induced rat lung injury | Reduction in injury and improvement in recovery | Reduced levels of edema, neutrophil, and alveolar IL-6 concentrations | [38] |
| BM-MSC-derived CM | Rat lung IRI | Protection against lung IRI | Decrease in both pro-inflammatory cytokines and infiltrating inflammatory cells, and increase in both M2-like macrophages and regulatory T cells | [39] |
| AdMSC-derived CM | LPS-induced mouse lung injury | Reduction in ARDS indices | Reduced endothelial barrier hyperpermeability and activation of pro-inflammatory and pro-apoptotic pathways in endothelium. | [40] |
| AMSC-derived CM | In vitro model of human lung IRI | Attenuation of IRI effects by improving the efficacy of in vitro EVLP | Increase in anti-inflammatory factors and up-regulation of anti-apoptotic factors | [41] |
| BM-MSCs and AdMSC-derived CM | Rat and human alveolar epithelial cell injury | Decreased cell injury | Decrease in pro-inflammatory factors and increase in anti-inflammatory factors; inhibition of p38 MAPK and translocation of Bcl-2 to the nucleus; Increased expression of cytoprotective glucose-regulated proteins | [43] |
| MSCs | Swine lung IRI | Attenuation of ischemic injury in donor lungs during EVLP and attenuation of IRI after transplantation | Increased levels of HGF and IL-4 and decreased levels of TNFα and cell death markers | [65] |
| BM-MSCs | HCL- and LPS-induced rat lung injury | Decreased inflammation | Decrease in proinflammatory cytokines, neutrophil infiltration, hemorrhage and interstitial edema |
[122] |
| UC-MSCs and UC-MSC-derived EVs | Rat neonatal hyperoxic lung injuries | Attenuation of hyperoxic lung injuries | Increased alveolarization and angiogenesis; decrease in alveolar epithelial cell death, macrophages and cytokines in lung |
[123] |
| BM-MSC-derived EVs | Mouse pulmonary arterial hypertension | Reduction in pulmonary vascular remodeling and right ventricle hypertrophy | Increased levels of anti-inflammatory and anti-proliferative miRs including miRs-34a,-122,-124, and -127. | [124] |
| BM-MSCs | Rat lung IRI | Attenuation of lung pathologic injury | Reduced myeloperoxidase production, decreased levels of of pro-inflammatory cytokine and cell apoptosis in lung tissue | [125] |
| BM-MSCs | E. coli-induced rat pneumonia | Reduction in lung injury; improvement in survival; reduction in lung bacterial load and suppression of inflammation | Enhanced macrophage phagocytic capacity and increase in lung and systemic concentrations of the antimicrobial peptide LL37 | [126] |
| BM-MSCs | Hyperoxia-induced rat lung injury | Mitigation of emphysema | Increased number of alveoli and decrease in α-SMA expression by myofibroblasts | [127] |
| BM-MSCs and BM-MSC-derived CM | Cigarette-smoke-induced rat emphysema | Alleviation of emphysema and increase in the number of small pulmonary vessels | Decrease in pulmonary artery medial wall thickness and reduction in apoptosis in lungs with emphysema | [128] |
| BM-MSCs and BM-MSC-derived CM | LPS-induced mouse lung injury | Resolution of lung injury by attenuating lung inflammation | Decrease in neutrophils and increase in M2 in BAL | [129] |
| BM-MSCs and BM-MSC-derived CM | Mouse chronic obstructive pulmonary disease | Reduction in injury | Reduced levels of inflammation, fibrosis and apoptotic and increased production of HGF | [130] |
| AdMSC-derived EVs | Elastase-induced mouse emphysema | Reduction in lung emphysema | Increased levels of FGF2 | [131] |
| BM-MSCs | Bleomycin-induced rat pulmonary fibrosis | Decreased fibrosis | Attenuation of NRF2, NQO1, HO-1, γ-GCS, lipid peroxidation, and increase in SOD activity | [132] |
| UC-MSCs | Rat lung IRI | Reduction in Oxidative stress damage and inflammation | Reduced levels of MPO activity and neutrophil markers; reduction in reactive oxygen species production | [133] |
| AdMSCs and AdMSC-derived CM | Sulfur mustard-induced mouse lung injury | Reduction in progressive histopathologic changes in the lung | Reducd levels of both M1 and M2 cells, TNF-α and IL-1β | [134] |
| BM-MSC-derived CM | Bleomycin-induced rat pulmonary fibrosis | Protection against lung fibrosis | Decrease in lung inflammation, fibrotic scores, collagen deposition, and cell apoptosis | [135] |
| SHEDs and SHED-derived CM | Bleomycin-induced mouse pulmonary fibrosis | Attenuation of lung injury and improvement in survival rate | Reduced levels of pro-inflammatory factors and increased levels of anti-inflammatory factors and M2 cells | [136] |
| BM-MSCs | Swine lung transplantation | Improvement in dynamic lung compliance | Reduced intrapulmonary edema | [137] |
| BM-MSC-derived EVs | E. Coli-induced mouse lung Injury | Reduction in lung edema and inflammation | Decrease in lung protein permeability, neutrophils and macrophage inflammatory protein-2 levels in the BAL fluid; increase in KGF in BAL | [138] |
| AdMSCs | Rat lung IRI | Attenuation of lung damage after IRI | Suppression of oxidative stress and inflammatory reaction | [139] |
| UC-MSCs | Swine lung IRI | Attenuation of IRI by improving the efficacy of EVLP | Increased levels of VEGF and decreased concentration of circulating IL-8 | [140] |
| BM-MSCs | Human lung IRI and EVLP | Decreased cold ischemic injury | Decrease in pro-inflammatory cytokines and increase in anti-inflammatory cytokines | [30] |
| BM-MSCs and BM-MSC-derived CM | E. coli-induced human lung injury | Increase in alveolar fluid clearance in lungs during EVLP | KGF secretion | [31] |
| BM-MSCs | Human lungs rejected for transplantation and subjected to prolonged ischemic time | Restoration of alveolar fluid clearance | KGF secretion | [32] |
| BM-MSC-derived EVs | Human lungs rejected for transplantation | Increase in alveolar fluid clearance in donor lungs during EVLP | Improved airway and hemodynamic parameters | [141] |
| AdMSCs | Clinical trial | Attenuation of IRI and host immunological reaction towards the graft | Not determined | NCT04714801 |
| BM-MSCs | Clinical trial | Attenuation of graft rejection and bronchiolitis obliteran syndrome (BOS) | Not determined | NCT02181712 |
MSCs: mesenchymal stromal/stem cells; BM-MSCs: bone-marrow-derived MSCs; AMSCs: amnion-derived MSCs; UC-MSCs: umbilical-cord-derived MSCs; AdMSCs: adipose-derived MSCs; SHEDs: stromal/stem cells from human exfoliated deciduous teeth; IRI: ischemia-reperfusion injury; EVLP: ex vivo lung perfusion; CM: conditioned medium; EVs: extracellular vesicles; BAL: bronchoalveolar lavage; ARDS: acute respiratory distress syndrome.