Pediatr Surg Int

. 2023 Nov 13;39(1):291.

 doi: 10.1007/s00383-023-05578-9. https://pubmed.ncbi.nlm.nih.gov/37955723/

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

Matisse Blundell ^1 2, Fabian Doktor ^1 2, Rebeca L Figueira ^1 2, Kasra Khalaj ^1 2, George Biouss ^1 2, Lina Antounians ^1 2, Augusto Zani ^3 4 5

Affiliations expand

• PMID: 37955723
• DOI: 10.1007/s00383-023-05578-9

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.

Keywords: Fetal brain; Hypoxia; Lung development; Perinatal brain injury; Pulmonary hypoplasia.

© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.