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Research: Fetal lung regeneration using stem cell-derived extracellular vesicles: A new frontier for pulmonary hypoplasia secondary to congenital diaphragmatic hernia

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Research: Fetal lung regeneration using stem cell-derived extracellular vesicles: A new frontier for pulmonary hypoplasia secondary to congenital diaphragmatic hernia

Prenat Diagn

. 2022 Feb 21. doi: 10.1002/pd.6117. Online ahead of print.

Fetal lung regeneration using stem cell-derived extracellular vesicles: A new frontier for pulmonary hypoplasia secondary to congenital diaphragmatic hernia

Rebeca Lopes Figueira 1 2Lina Antounians 1 2Elke Zani-Ruttenstock 1 2Kasra Khalaj 1 2Augusto Zani 1 2 3Affiliations expand https://pubmed.ncbi.nlm.nih.gov/35191057/

Abstract

The poor outcomes of babies with congenital diaphragmatic hernia (CDH) are directly related to pulmonary hypoplasia, a cosndition characterized by impaired lung development. Although the pathogenesis of pulmonary hypoplasia is not fully elucidated, there is now evidence that CDH patients have missing or dysregulated microRNAs (miRNAs) that regulate lung development. A prenatal therapy that supplements these missing/dysregulated miRNAs could be a strategy to rescue normal lung development. Extracellular vesicles (EVs), also known as exosomes when of small dimensions, are lipid-bound nanoparticles that can transfer their heterogeneous cargo (proteins, lipids, small RNAs) to target cells to induce biological responses. Herein, we review all studies that show evidence for stem cell-derived EVs as a regenerative therapy to rescue normal development in CDH fetal lungs. Particularly, we report studies showing that administration of EVs derived from amniotic fluid stem cells (AFSC-EVs) to models of pulmonary hypoplasia promotes fetal lung growth and maturation via transfer of miRNAs that are known to regulate lung developmental processes. We also describe that stem cell-derived EVs exert effects on vascular remodeling, thus possibly preventing postnatal pulmonary hypertension. Finally, we discuss future perspectives and challenges to translate this promising stem cell EV-based therapy to clinical practice. This article is protected by copyright. All rights reserved.

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