Table 2 Gene therapy approaches to improve MSC potency in lung diseases
From: Strategies to improve the therapeutic effects of mesenchymal stromal cells in respiratory diseases
Lung disease model | Upregulated gene | MSC source | MSC dose | Time of MSC administration | In vivo effects (compared to wild-type MSC) | Reference |
|---|---|---|---|---|---|---|
LPS-induced ARDS | Developmental endothelial locus-1 | Murine bone marrow | 5 × 106 | 1 h after LPS injection | ↓ Lung injury histopathological index ↓ Pulmonary edema ↓ Neutrophil counts, TNF-α levels, and protein concentration in BALF ↓ Myeloperoxidase activity in lung homogenates | [46] |
ST2 receptor gene | Human adipose tissue | 106 | 6 h after LPS injection | ↑ IL-10 mRNA levels in lung homogenate ↓ IL-1β and IFN-γ mRNA levels in lung homogenate ↓ LPS-mediated production of circulating IL-33 ↓ TNF-α and IL-6 levels and protein concentration in BALF ↓ Polymorphonuclear cells in interstitial space | [47] | |
Angiotensin-converting enzyme-2 | Murine bone marrow | 5 × 105 | 4 h after LPS injection | ↓ Lung injury histopathological index ↓ Total cell counts in BALF ↓ Neutrophil counts in BALF ↓ Ang-2, IL-1β and IL-6 protein levels in lung homogenates ↑ IL-10 protein levels in lung homogenates ↓ IL-1β serum levels ↓ Vascular permeability | [48] | |
Radiation-induced ARDS | Manganese superoxide dismutase | Human bone marrow | 106 | 4 h after exposure to radiation | ↓ Lung injury histopathological index ↓ Pulmonary edema ↓ TNF-α and IL-6 serum levels ↑ IL-10 serum levels ↓ Hydroxyproline in lung homogenates ↓ Neutrophil counts in BALF ↓ Lipid peroxidation ↓ Cell apoptosis in lung tissue ↑ Survival rates | [49] |
Hypoxia-induced pulmonary hypertension | Heme oxygenase-1 isoform | Murine bone marrow | 106 | 2 weeks after exposure to hypoxia | ↓ Right ventricle systolic pressure ↓ Right ventricle hypertrophy | [50] |