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Updated: Aug 14, 2025
Intratracheal Instillation of Stem Cells in Term Neonatal Rats
Published on: May 4, 2020
MSC-EXO and tempol ameliorate bronchopulmonary dysplasia in newborn rats by activating HIF-1α
Juanmei Wang1,2, Aimin Zhang1, Furong Huang1
1Department of Pediatrics, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China.
Insights
Combined treatment with mesenchymal stem cells-derived exosomes (MSC-EXO) and tempol effectively reverses lung injury and improves lung function in bronchopulmonary dysplasia (BPD) rat models by activating HIF-1α.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Neonatal Physiology
Background:
- Bronchopulmonary dysplasia (BPD) is a significant cause of illness and death in premature infants.
- Understanding novel therapeutic strategies for BPD is crucial.
Purpose of the Study:
- To investigate the therapeutic effects of combining mesenchymal stem cells-derived exosomes (MSC-EXO) with tempol on BPD.
- To elucidate the underlying mechanisms of this combined treatment.
Main Methods:
- Mesenchymal stem cells-derived exosomes (MSC-EXO) were extracted and characterized.
- Pulmonary function, lung morphology, vascularization, oxidative stress markers, and inflammatory cytokines were assessed in a rat model of BPD.
- Key protein expressions including HIF-1α, VEGF, p-PI3K, and p-AKT were analyzed.
Main Results:
- Combined MSC-EXO and tempol treatment reversed BPD-induced decreases in lung function (TV, MV, PIF, Cdyn) and alveolar simplification.
- The treatment restored pulmonary vascular density (CD31), reduced oxidative stress (MDA, TAOC, SOD), and decreased inflammation (IL-1β, IL-17, IL-6, IFN-γ).
- Expression of HIF-1α, VEGF, p-PI3K, and p-AKT was upregulated following combined therapy.
Conclusions:
- Combined MSC-EXO and tempol treatment ameliorates lung tissue injury and enhances pulmonary vascular remodeling in BPD rats.
- The therapy effectively restores lung function and mitigates oxidative stress.
- These beneficial effects are mediated through the activation of HIF-1α signaling pathways.
Background:
Bronchopulmonary dysplasia (BPD) is a major complication of premature infants and an important cause of morbidity and mortality. This study investigates the effect of the combination of mesenchymal stem cells-derived exosomes (MSC-EXO) and tempol on BPD and analyzes its mechanism.
Methods:
MSC-EXO was extracted by centrifugation and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis, and western blot analysis (WB). Tidal volume (TV), minute ventilation (MV), peak inspiratory flow (PIF), and dynamic pulmonary compliance (Cdyn) of rats were measured by BuxCo pulmonary function experimental platform. Hematoxylin-eosin staining was performed to observe the lung morphology and radical alveolar count (RAC) and mean linear intercept (MLI) were assessed. Immunofluorescence (IF) was conducted to detect the expression of CD31 and α-SMA in pulmonary blood vessels. The kits were used to calculate malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (TAOC) concentration in lung tissue. Enzyme linked immunosorbent assay was applied to detect the levels of IL-1β, IL-17, IL-6, and IFN-γ in bronchoalveolar lavage fluid. In addition, the expressions of HIF-1α, vascular endothelial growth factor (VEGF), p-PI3K, and p-AKT were analyzed by WB and IF.
Results:
We successfully extracted and identified MSC-EXO. In BPD rats, TV, MV, PIF, and Cdyn decreased, alveoli were simplified, and the number of interalveoli small vessels, blood vessel density decreased. Moreover, RAC, CD31, TAOC, and SOD decreased, and MLI, α-SMA, MDA, IL-1β, IL-17, IL-6, and IFN-γ increased, which was reversed by the combination of MSC-EXO and tempol treatment after combined treatment. In addition, the expression levels of HIF-1α, VEGF, p-PI3K, and p-AKT were increased after combined treatment.
Conclusions:
Combined treatment could improve lung tissue injury, promote pulmonary vascular remodeling, restore lung function, and inhibit oxidative stress in BPD rats. These effects were achieved through activation of HIF-1α.
