Table 1.
Stem/progenitor cell pre-clinical trials in experimental neonatal lung diseases
| Cell Type | Source/Route/Control cell | Animal Model | Age of Animals | Outcomes | Reference |
|---|---|---|---|---|---|
| MSC | BM/IV/no | 95% hyperoxia (rat) | P-10 | Reduced levels of TNF-alpha and TGF-beta1, increased radial alveolar count. | (16) |
| MSC MSC-CM |
BM/IT/PASMC | 95% hyperoxia (rat) | P-14 |
in vitro: preferential MSC migration toward O2-damaged lungs. MSC-CM prevented O2-induced AEC2 apoptosis, accelerated AEC2 wound healing and enhanced endothelial cord formation. in vivo: attenuated alveolar and vascular injury, and PH. |
(18) |
| MSC | BM/IV/no | 95% hyperoxia (rat) | P-3, P-7, P-14 | Improved weight gain, prevented alveolar growth arrest and suppressed lung inflammation. | (19) |
| MSC-CM | BM/IP/lung fibroblasts | 95% hyperoxia (rat) | P-14 | Preserved alveolar growth. CM from O2-exposed, preconditioned BMSCs exerted more potent therapeutic potential and prevented PH. | (39) |
| MSC MSC-CM |
BM/IV/PASMC for CM | 75% hyperoxia (mouse) | P-14 | MSCs reduced alveolar loss and lung inflammation, prevented PH. MSC-CM had a more pronounced effect, prevented alveolar and lung vascular injury. | (17) |
| MSC | BM/IP/no | 60% hyperoxia (mouse) | P-45 |
in vitro: co-culturing of injured lung tissue increased migration potential of BMSC and SP-C expression. in vivo: BMSC home to injured lung, express SP-C, improve pulmonary architecture, attenuate pulmonary fibrosis and increase survival rate. |
(20) |
| MSC-CM | BM/IV/lung fibroblasts | 75% hyperoxia (mouse) | P-14 | Reversed parenchymal fibrosis and peripheral PA devascularisation, partially reversed alveolar injury, normalized lung function, reversed PH and RVH and attenuated peripheral PA muscularization. | (37) |
| MSC MSC-CM |
BM/IV/PASMC | 75% hyperoxia (mouse) | P-10 |
in vitro: MSC-CM increased BASCs growth. in vivo: MSCs & MSC-CM increased BASCs in lungs. |
(41) |
| MSC MSC-CM |
BM/IT/no | 90% hyperoxia (rat) | P-16, P-33, P-100 | Improved alveolarization and lung vascular growth with MSC and MSC-CM up to 3 months post-treatment. Decreased inflammation and up-regulation of angiogenic factors. | (38) |
| MSC | UCB/IT & IP/no | 95% hyperoxia (rat) | P-14 | IT & IP: attenuated the increase in TUNEL-positive cells, myeloperoxidase activity, and IL-6 mRNA level. IT: improved alveolarization and decreased lung collagen, TNF-alpha and TGF-beta mRNA, alpha-SMA protein. |
(26) |
| MSC | UCB/IT/no | 95% hyperoxia (rat) | P-14 | Improved alveolarization, decreased lung collagen, and attenuated lung inflammation (decreased myeloperoxidase activity, TNF-alpha, IL-1beta, IL-6, TGF-beta mRNA, up- regulation of cytosolic and membrane p4phox) in a dose dependent manner. | (27) |
| MSC & Pericytes | Umbilical cord & UCB/IT/Human neonatal dermal fibroblasts | 95% hyperoxia (rat) | P-22, P-35, 6 months | Improved alveolarization and lung vascular growth with whole cell and cell-free CM. Prevention and rescue. Efficacy and safety up to 6 months post-treatment. | (28) |
| Myeloid progenitor | BM/IV/embryonic EPC, mouse embryonic fibroblasts | 80% hyperoxia (mice) | P-21 | Restored lung structure. | (34) |
| Epithelial | Amnion/IV/no | LPS (sheep) | Improved lung function and structure (lung volume, tissue-to- airspace ratio, and septal crest density), reduced inflammatory cytokines (TNF-alpha, IL-1beta, IL-6). | (29) | |
| Epithelial | Amnion/IV/no | Ventilation (sheep) | Attenuated lung fibrosis and normalized secondary septal crests. Differentiated into AEC1 and AEC2 in the injured lung. | (30) |
Abbreviations: AEC1/2: alveolar epithelial type I/II cell, BASC: bronchioalveolar stem cells, BM: bone marrow, CM: conditioned media, EPC: endothelial progenitor cell, IV: intravenous, IT: intratracheal, IP: intraperitoneal, LPS: lipopolysaccharide, P-(n): postnatal day-(n), PA: pulmonary artery, PASMC: PA smooth muscle cells, PH: pulmonary hypertension, RVH: right ventricular hypertrophy, SMA: smooth muscle actin, SP-C: surfactant protein C, TNF: tumor necrosis factor, TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling, UCB: umbilical cord blood.