Anti-inflammatory effects of antenatal administration of stem cell derived extracellular vesicles in the brain of rat fetuses with congenital diaphragmatic hernia.
Fetal brain
Hypoxia
Lung development
Perinatal brain injury
Pulmonary hypoplasia
Journal
Pediatric surgery international
ISSN: 1437-9813
Titre abrégé: Pediatr Surg Int
Pays: Germany
ID NLM: 8609169
Informations de publication
Date de publication:
13 Nov 2023
13 Nov 2023
Historique:
accepted:
22
10
2023
medline:
14
11
2023
pubmed:
13
11
2023
entrez:
13
11
2023
Statut:
epublish
Résumé
Congenital diaphragmatic hernia (CDH) survivors may experience neurodevelopmental impairment, whose etiology remains elusive. Preclinical evidence indicates that amniotic fluid stem cell extracellular vesicle (AFSC-EV) administration promotes lung development but their effects on other organs are unknown. Herein, we investigated the brain of rat fetuses with CDH for signs of inflammation and response to AFSC-EVs. CDH was induced by maternal nitrofen administration at E9.5. At E18.5, fetuses were injected intra-amniotically with saline or AFSC-EVs (isolated by ultracentrifugation, characterized as per MISEV guidelines). Fetuses from vehicle-gavaged dams served as controls. Groups were compared for: lung hypoplasia, TNFa and IL-1B brain expression, and activated microglia (Iba1) density in the subgranular zone (SGZ). CDH lungs had fewer airspaces compared to controls, whereas AFSC-EV-treated lungs had rescued branching morphogenesis. Fluorescently labeled AFSC-EVs injected intra-amniotically into CDH fetuses had fluorescent signal in the brain. Compared to controls, the brain of CDH fetuses had higher TNFa and IL-1B levels, and increased activated microglia density. Conversely, the brain of AFSC-EV treated fetuses had inflammatory marker expression levels and microglia density similar to controls. This study shows that the brain of rat fetuses with CDH has signs of inflammation that are abated by the intra-amniotic administration of AFSC-EVs.
Identifiants
pubmed: 37955723
doi: 10.1007/s00383-023-05578-9
pii: 10.1007/s00383-023-05578-9
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
291Subventions
Organisme : Canadian Institutes of Health Research (CIHR) Project Grant
ID : 175300
Organisme : SickKids Congenital Diaphragmatic Hernia Fund
ID : R00DH00000
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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