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Published in: Pediatric Surgery International 1/2023

01-12-2023 | Diaphragmatic Hernia | Original Article

Anti-inflammatory effects of antenatal administration of stem cell derived extracellular vesicles in the brain of rat fetuses with congenital diaphragmatic hernia

Authors: Matisse Blundell, Fabian Doktor, Rebeca L. Figueira, Kasra Khalaj, George Biouss, Lina Antounians, Augusto Zani

Published in: Pediatric Surgery International | Issue 1/2023

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Abstract

Purpose

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.

Methods

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).

Results

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.

Conclusion

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.
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Metadata
Title
Anti-inflammatory effects of antenatal administration of stem cell derived extracellular vesicles in the brain of rat fetuses with congenital diaphragmatic hernia
Authors
Matisse Blundell
Fabian Doktor
Rebeca L. Figueira
Kasra Khalaj
George Biouss
Lina Antounians
Augusto Zani
Publication date
01-12-2023
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Surgery International / Issue 1/2023
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI
https://doi.org/10.1007/s00383-023-05578-9

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