BOB Winner Presentation - Dr. Rebeca Figueira - EUPSA

Fetal lung vascular remodeling predisposes fetuses with CDH to postnatal pulmonary hypertension, which plays a central role in the poor outcomes of these babies.

There is consensus that the prenatal period offers a window of opportunity to promote normal lung development in CDH.

No antenatal treatments tested to date have been successful in CDH.

AFSCVs promote growth and maturation in fetal hypoplastic lungs via the release of RNA cargo.

EVs were isolated using ultracentrifugation and characterized in accordance with the International Society of Extracellular Vesicles guidelines.

A nitrophen model of CDH in rats was used with antenatal AFSCV injection into the amniotic sac at E18.

The Fulton index expresses the degree of right ventricular hypertrophy and is an indirect marker of pulmonary hypertension.

Vascular density was rescued back to normal levels after AFSCV administration in rat CDH lungs.

Vascular remodeling was attenuated in CDH treated lungs.

Angiogenic factors were rescued back to normal levels after AFSCV treatment in rat lungs.

AFSCVs attenuated the severity of right ventricular hypertrophy in CDH hearts.

Vascular density was restored by AFSCV treatment in human fetal lung explants with hypoplasia.

Vascular remodeling was attenuated in hypoplastic treated human lung explants.

Angiogenic factors were rescued back to normal levels after AFSCV treatment in human lung explants.

Single nucleus RNA sequencing revealed a striking difference between control and CDH in the pattern and distribution of endothelial cells, which was rescued to normal distribution following AFSCV treatment.

245 differentially expressed genes were identified in endothelial cells.

Genes regulating vasculogenesis and angiogenesis were downregulated in CDH lungs and upregulated in CDH treated lungs.

AFSCV cargo contains microRNAs that control processes like angiogenesis and proliferation and migration of vascular endothelial cells.

AFSCVs rescue vascular development and attenuate vascular remodeling in rat and human fetal hypoplastic lungs.

AFSCVs modulate angiogenic processes and rescue the expression of genes involved in lung vascular development.