In:
Current Stem Cell Research & Therapy, Bentham Science Publishers Ltd., Vol. 19 ( 2023-10-04)
Abstract:
Mesenchymal stem cell-derived exosomes (MSC-Exos) therapies have
shown prospects in preclinical models of pathologies relevant to neonatal medicine, such as bronchopulmonary dysplasia (BPD). Adipose-derived stem cells (ADSCs) have been recognized as
one of the most promising stem cell sources. Autophagy plays a key role in regulating intracellular conditions, maintaining cell growth and development, and participating in the pathogenesis of
BPD. background: Mesenchymal stem cells derived exosomes (MSC-Exos) therapies have shown prospects in preclinical models of pathologies relevant to neonatal medicine, such as bronchopulmonary dysplasia (BPD). Adipose-derived stem cells (ADSCs) have been recognized as one of the most promising stem cell sources. Autophagy plays a key role in regulating intracellular conditions, maintaining cell growth and development, and participating in the pathogenesis of BPD. Objectives:: To investigate the potential therapeutic role of ADSC-Exos on BPD and to illustrate
the role of autophagy in this process. Method:: ADSC-Exos was isolated from media conditioned of ADSCs by ultracentrifugation and
characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting (WB). Newborn rats were exposed to hyperoxia (90% O2) to mimic BPD,
treated with ADSC-Exos by intratracheal or intravenous administration on postnatal day 4 (P4) and returned to room air on P7 until P14. Treated animals and appropriate controls were harvested
on P7 and P14 for assessment of pulmonary parameters. Results:: Hyperoxia-exposed rats were presented with pronounced alveolar simplification with decreased
radial alveolar count (RAC) and increased mean linear intercept (MLI), impaired vascular development with low vascular endothelial growth factor (VEGF) and CD31 expression, and stimulated
inflammation with increased expression of TNF-α, IL-1β, and IL-6, and decreased expression of IL-10. Meanwhile, the rats with hyperoxia exposure blocked autophagic flux with lower
levels of Beclin1, LC3B, LC3BII/I ratio and higher levels of p62. ADSC-Exos administration protected the neonatal lung tissues from the hyperoxia-induced arrest of alveolar and vascular development,
reduced inflammation, and facilitated autophagy. Intratracheal administration was more efficacious than intravenous administration. result: Hyperoxia-exposed rats presented with pronounced alveolar simplification with decreased radial alveolar count (RAC) and increased mean linear intercept (MLI), impaired vascular development with low vascular endothelial growth factor (VEGF) and CD31 expression, and stimulated inflammation with increased expression of TNF-α, IL-1β, and IL-6, and decreased expression of IL-10. Meanwhile, the rats with hyperoxia exposure blocked autophagic flux with lower levels of Beclin1, LC3B, LC3BII/I ratio, and higher levels of p62. ADSC-Exos administration protected the neonatal lung tissues from the hyperoxia-induced arrest of alveolar and vascular development, reduced inflammation, and facilitated autophagy. Intratracheal administration was more efficacious than intravenous administration. Conclusion:: The intratracheal administration of ADSC-Exos significantly improved alveolarization
and pulmonary vascularization arrest in hyperoxia-induced BPD, which was associated with facilitating autophagy in part. other: none
Type of Medium:
Online Resource
ISSN:
1574-888X
DOI:
10.2174/011574888X260261230928094309
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2023
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