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Updated: Nov 8, 2025
Intratracheal Instillation of Stem Cells in Term Neonatal Rats
Published on: May 4, 2020
Fetal lung underdevelopment is rescued by administration of amniotic fluid stem cell extracellular vesicles in
Lina Antounians1,2, Vincenzo D Catania1,2, Louise Montalva1,2
1Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, M5G 0A4, Canada.
Insights
Amniotic fluid stem cell-derived extracellular vesicles (AFSC-EVs) show promise for treating fetal lung underdevelopment. These EVs promote lung growth and maturation, offering a potential therapy for pulmonary hypoplasia and congenital diaphragmatic hernia.
Area of Science:
- Regenerative Medicine
- Developmental Biology
- Pulmonology
Background:
- Fetal lung underdevelopment, or pulmonary hypoplasia, is a severe condition often linked to congenital diaphragmatic hernia (CDH).
- Current treatments for CDH lack methods to enhance fetal lung growth, leading to high morbidity and mortality rates.
- There is a critical unmet need for therapies that promote fetal lung development and maturation.
Purpose of the Study:
- To investigate the potential of extracellular vesicles (EVs) derived from amniotic fluid stem cells (AFSCs) as a therapeutic strategy for fetal lung underdevelopment.
- To evaluate the efficacy of AFSC-EVs in promoting lung growth and maturation in preclinical models of pulmonary hypoplasia.
- To elucidate the mechanism of action underlying the regenerative effects of AFSC-EVs.
Main Methods:
- Utilized rodent models of pulmonary hypoplasia, including primary epithelial cells, organoids, explants, and in vivo studies.
- Administered AFSC-derived EVs to fetal rodents to assess effects on lung development.
- Employed in vitro models with human lung injury samples to confirm the regenerative capacity of human AFSC-EVs.
- Analyzed the RNA cargo within AFSC-EVs, focusing on microRNAs involved in lung development.
Main Results:
- AFSC-EV administration significantly promoted branching morphogenesis and alveolarization in fetal rodent lungs.
- Treatment with AFSC-EVs rescued tissue homeostasis and stimulated epithelial and fibroblast differentiation.
- Human AFSC-EVs demonstrated efficacy in restoring pulmonary epithelial homeostasis in in vitro models of lung injury.
- AFSC-EVs were found to deliver RNA cargo, including microRNAs like the miR17-92 cluster, which are crucial for lung development.
Conclusions:
- AFSC-derived EVs possess significant regenerative potential for underdeveloped fetal lungs.
- This stem cell-based approach offers a promising therapeutic avenue for pulmonary hypoplasia and related conditions.
- The therapeutic effects are mediated by the transfer of specific RNA molecules, highlighting a novel mechanism for promoting lung development.
Abstract:
Fetal lung underdevelopment, also known as pulmonary hypoplasia, is characterized by decreased lung growth and maturation. The most common birth defect found in babies with pulmonary hypoplasia is congenital diaphragmatic hernia (CDH). Despite research and clinical advances, babies with CDH still have high morbidity and mortality rates, which are directly related to the severity of lung underdevelopment. To date, there is no effective treatment that promotes fetal lung growth and maturation. Here, we describe a stem cell-based approach in rodents that enhances fetal lung development via the administration of extracellular vesicles (EVs) derived from amniotic fluid stem cells (AFSCs). Using fetal rodent models of pulmonary hypoplasia (primary epithelial cells, organoids, explants, and in vivo), we demonstrated that AFSC-EV administration promoted branching morphogenesis and alveolarization, rescued tissue homeostasis, and stimulated epithelial cell and fibroblast differentiation. We confirmed this regenerative ability in in vitro models of lung injury using human material, where human AFSC-EVs obtained following good manufacturing practices restored pulmonary epithelial homeostasis. Investigating EV mechanism of action, we found that AFSC-EV beneficial effects were exerted via the release of RNA cargo. MicroRNAs regulating the expression of genes involved in lung development, such as the miR17-92 cluster and its paralogs, were highly enriched in AFSC-EVs and were increased in AFSC-EV-treated primary lung epithelial cells compared to untreated cells. Our findings suggest that AFSC-EVs hold regenerative ability for underdeveloped fetal lungs, demonstrating potential for therapeutic application in patients with pulmonary hypoplasia.
