Evidence map›Paper›PMID 36103370›Full record

ArticleStem cells translational medicine2022

Treatment with Amniotic Fluid Stem Cell Extracellular Vesicles Promotes Fetal Lung Branching and Cell Differentiation at Canalicular and Saccular Stages in Experimental Pulmonary Hypoplasia Secondary to Congenital Diaphragmatic Hernia.

Kasra Khalaj, Rebeca Lopes Figueira, Lina Antounians, Sree Gandhi, Matthew Wales, Louise Montalva, George Biouss, Augusto Zani

Open access · goldAbstract read
In one paragraph

Article in Stem cells translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
6.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
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  8. A new hope for pulmonary hypoplasia: amniotic fluid stem cell extracellular vesicles?Extracellular vesicles and circulating nucleic acids · 2025
    Article
  9. Article
  10. Comparison of current to past outcomes in congenital diaphragmatic hernia using MRI observed-to-expected total fetal lung volume.Journal of perinatology : official journal of the California Perinatal Association · 2024
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Kasra KhalajDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada.ORCID 0000-0002-5947-6500
Rebeca Lopes FigueiraDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada.ORCID 0000-0002-7102-1322
Lina AntouniansDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada.ORCID 0000-0002-8307-3306
Sree GandhiDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada.
Matthew WalesDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada.
Louise MontalvaDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada.ORCID 0000-0001-8357-9609
George BioussDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada.
Augusto ZaniDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada.ORCID 0000-0003-2283-9846
Hospital for Sick Children · CAUniversity of Toronto · CA

Funding

CIHR 175300CIHR 176535
6 · The paper itself

Abstract

Pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by impaired branching morphogenesis and differentiation. We have previously demonstrated that administration of extracellular vesicles derived from rat amniotic fluid stem cells (AFSC-EVs) rescues development of hypoplastic lungs at the pseudoglandular and alveolar stages in rodent models of CDH. Herein, we tested whether AFSC-EVs exert their regenerative effects at the canalicular and saccular stages, as these are translationally relevant for clinical intervention. To induce fetal pulmonary hypoplasia, we gavaged rat dams with nitrofen at embryonic day 9.5 and demonstrated that nitrofen-exposed lungs had impaired branching morphogenesis, dysregulated signaling pathways relevant to lung development (FGF10/FGFR2, ROBO/SLIT, Ephrin, Neuropilin 1, β-catenin) and impaired epithelial and mesenchymal cell marker expression at both stages. AFSC-EVs administered to nitrofen-exposed lung explants rescued airspace density and increased the expression levels of key factors responsible for branching morphogenesis. Moreover, AFSC-EVs rescued the expression of alveolar type 1 and 2 cell markers at both canalicular and saccular stages and restored markers of club, ciliated epithelial, and pulmonary neuroendocrine cells at the saccular stage. AFSC-EV-treated lungs also had restored markers of lipofibroblasts and PDGFRA+ cells to control levels at both stages. EV tracking showed uptake of AFSC-EV RNA cargo throughout the fetal lung and an mRNA-miRNA network analysis identified that several miRNAs responsible for regulating lung development processes were contained in the AFSC-EV cargo. These findings suggest that AFSC-EV-based therapies hold potential for restoring fetal lung growth and maturation in babies with pulmonary hypoplasia secondary to CDH.

Indexed as

Extracellular VesiclesHernias, Diaphragmatic, CongenitalMicroRNAsAmniotic FluidAnimalsbeta CateninCell DifferentiationDisease Models, AnimalEphrinsFibroblast Growth Factor 10LungNeuropilin-1Phenyl EthersRatsRats, Sprague-DawleyRNA, Messengerbeta CateninEphrinsFgf10 protein, ratFibroblast Growth Factor 10MicroRNAsNeuropilin-1nitrofenPhenyl EthersRNA, Messengercongenital diaphragmatic herniaexosomeextracellular vesiclesfetal medicinelung developmentmicroRNApulmonary hypoplasiaregenerative medicine

Identifiers

PMID36103370
PMCPMC9585953
OpenAlexW4295745582

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.