Evidence map›Paper›PMID 39058789›Full record

ArticleScience advances2024

Fetal hypoplastic lungs have multilineage inflammation that is reversed by amniotic fluid stem cell extracellular vesicle treatment.

Lina Antounians, Rebeca Lopes Figueira, Bharti Kukreja, Michael L Litvack, Elke Zani-Ruttenstock, Kasra Khalaj, Louise Montalva, Fabian Doktor, Mikal Obed, Matisse Blundell and 8 more

Abstract read
In one paragraph

Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  10. A new hope for pulmonary hypoplasia: amniotic fluid stem cell extracellular vesicles?Extracellular vesicles and circulating nucleic acids · 2025
    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

18 authors.

Lina AntouniansDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.ORCID 0000-0002-8307-3306
Rebeca Lopes FigueiraDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.
Bharti KukrejaNeurosciences and Mental Health Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.
Michael L LitvackTranslational Medicine Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.ORCID 0000-0001-9236-5493
Elke Zani-RuttenstockDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.ORCID 0000-0003-1391-8921
Kasra KhalajDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.ORCID 0000-0002-5947-6500
Louise MontalvaDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.
Fabian DoktorDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.
Mikal ObedDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.ORCID 0000-0001-7102-2547
Matisse BlundellDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.ORCID 0000-0002-6704-7714
Taiyi WuNeurosciences and Mental Health Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.ORCID 0000-0001-5084-6520
Cadia ChanGenetics and Genome Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.ORCID 0000-0002-4810-8366
Richard WagnerDepartment of Pediatric Surgery, Leipzig University, Leipzig 04109, Germany.ORCID 0000-0002-3035-2619
Martin LacherDepartment of Pediatric Surgery, Leipzig University, Leipzig 04109, Germany.ORCID 0000-0002-4616-9464
Michael D WilsonGenetics and Genome Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.ORCID 0000-0002-4015-3066
Martin PostTranslational Medicine Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.ORCID 0000-0003-4258-9303
Brian T KalishNeurosciences and Mental Health Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.ORCID 0000-0003-3235-6856
Augusto ZaniDevelopmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto M5G 0A4, Canada.ORCID 0000-0003-2283-9846

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antenatal administration of extracellular vesicles from amniotic fluid stem cells (AFSC-EVs) reverses features of pulmonary hypoplasia in models of congenital diaphragmatic hernia (CDH). However, it remains unknown which lung cellular compartments and biological pathways are affected by AFSC-EV therapy. Herein, we conducted single-nucleus RNA sequencing (snRNA-seq) on rat fetal CDH lungs treated with vehicle or AFSC-EVs. We identified that intra-amniotically injected AFSC-EVs reach the fetal lung in rats with CDH, where they promote lung branching morphogenesis and epithelial cell differentiation. Moreover, snRNA-seq revealed that rat fetal CDH lungs have a multilineage inflammatory signature with macrophage enrichment, which is reversed by AFSC-EV treatment. Macrophage enrichment in CDH fetal rat lungs was confirmed by immunofluorescence, flow cytometry, and inhibition studies with GW2580. Moreover, we validated macrophage enrichment in human fetal CDH lung autopsy samples. Together, this study advances knowledge on the pathogenesis of pulmonary hypoplasia and further evidence on the value of an EV-based therapy for CDH fetuses.

Indexed as

Amniotic FluidExtracellular VesiclesLungAnimalsCell DifferentiationDisease Models, AnimalFemaleFetusHernias, Diaphragmatic, CongenitalHumansInflammationMacrophagesPregnancyRatsStem CellsStem Cell Transplantation

Identifiers

PMID39058789
PMCPMC11277482

What OpenQuestion holds

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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.