Safety, Efficacy and Bio-Distribution Analysis of Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells for Effective Treatment of Bronchopulmonary Dysplasia by Intranasal Administration in Mice Model

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 2521 - 2553

Published: Feb. 1, 2025

Exosomes (Exos) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) hold great potential for treating bronchopulmonary dysplasia (BPD); however, safety concerns and effects of intranasal administration remain unexplored. This study aimed to explore the hUC-MSCs Exos investigate efficacy bio-distribution repeated in neonatal BPD models. Characteristics were analyzed. A subcutaneous tumor formation assay using a single dose or was conducted Crl:NU-Foxn1nu mice. Vital signs, biochemical indices, pathological alterations, 18F-FDG microPET/CT analysis examined. Pulmonary pathology, three-dimensional reconstructions, ultrastructural structures, vivo ex imaging analyses, enzyme-linked immunoassay assays, reverse transcription-quantitative polymerase chain reaction analyses lung tissues all documented following administration. satisfied specifications. mice did not exhibit overt toxicity carcinogenicity after 60 days observation. Repeated effectively alleviated injuries, restored pulmonary ventilation reconstruction, recovered endothelial cell layer integrity analysis. steadily accumulated postnatal day 1 14. also interrupted epithelial-mesenchymal transition inflammation reactions As nanoscale, non-cellular therapy, an effective, noninvasive treatment BPD. approach free toxic, tumorigenic risks repaired alveolar damage while interrupting with

Language: Английский

The tryptophan metabolite 3-hydroxyanthranilic acid alleviates hyperoxia-induced bronchopulmonary dysplasia via inhibiting ferroptosis

Redox Biology, Journal Year: 2025, Volume and Issue: 82, P. 103579 - 103579

Published: March 9, 2025

Bronchopulmonary dysplasia (BPD) is a prevalent chronic respiratory condition in preterm infants with an increasing incidence, severely affecting their survival rate and quality of life. Exploring the underlying mechanisms BPD helps to develop novel effective therapeutic strategies. In this study, integrated metabolomic analyses tracheal aspirates (TAs) from non-BPD infants, along lung tissues hyperoxia-induced experimental neonatal rats control rats, demonstrated that was associated significant reduction 3-hydroxyanthranilic acid (3-HAA), which confirmed be partly caused by tryptophan-metabolizing enzyme disorders. vivo vitro models were subsequently established assess efficacy 3-HAA relation BPD. Compared group, nebulization improved development suppressed inflammation rats. Limited proteolysis-small molecule mapping (LiP-SMap) proteomic analysis revealed involvement ferroptosis pathway mechanism alleviated injury. Ferroptosis identified detecting Fe2+ levels, malondialdehyde (MDA), 4-HNE, total aldehydes, mitochondrial morphology, ferroptosis-associated protein mRNA expression, dysregulation indeed ameliorated vivo. Furthermore, combination LiP-SMap, molecular docking, SPR Co-IP can bind directly FTH1 disrupt nuclear receptor coactivator 4 (NCOA4)-FTH1 interaction. conclusion, our study first reveal linked 3-HAA, could inhibit targeting FTH1, thereby alleviating injury alveolar type II epithelial cells, highlighting potential for clinical applications

Language: Английский