Evidence map›Paper›PMID 37904135›Full record

ArticleBMC medicine2023

Hypoxia enhances anti-fibrotic properties of extracellular vesicles derived from hiPSCs via the miR302b-3p/TGFβ/SMAD2 axis.

Milena Paw, Agnieszka A Kusiak, Kinga Nit, Jacek J Litewka, Marcin Piejko, Dawid Wnuk, Michał Sarna, Kinga Fic, Kinga B Stopa, Ruba Hammad and 6 more

Open access · goldAbstract read
In one paragraph

Article in BMC medicine, 2023. 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
6.2field-weighted citation impact, top 3% 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, 40 citations in OpenAlex.

  1. Article
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  6. Recent advances in biomarkers for cardiac fibrosis.Frontiers in cardiovascular medicine · 2026
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  16. Extracellular vesicle therapeutics for cardiac repair.Journal of molecular and cellular cardiology · 2025
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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

16 authors at 2 institutions in 2 countries.

Milena PawFaculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biology, Jagiellonian University, Kraków, Poland.
Agnieszka A KusiakFaculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biology, Jagiellonian University, Kraków, Poland.
Kinga NitFaculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biology, Jagiellonian University, Kraków, Poland.
Jacek J LitewkaFaculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biology, Jagiellonian University, Kraków, Poland.
Marcin Piejko3Rd Department of General Surgery, Jagiellonian University - Medical College, Kraków, Poland.
Dawid WnukFaculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biology, Jagiellonian University, Kraków, Poland.
Michał SarnaFaculty of Biochemistry, Biophysics and Biotechnology, Department of Biophysics, Jagiellonian University, Kraków, Poland.
Kinga FicMałopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland.
Kinga B StopaDoctoral School of Exact and Natural Sciences, Jagiellonian University, Kraków, Poland.
Ruba HammadFreiburg iPS Core Facility, Institute for Transfusion Medicine and Gene Therapy, Medical Center, University of Freiburg, Freiburg, Germany.
Olga Barczyk-WoznickaInstitute of Zoology and Biomedical Research, Department of Cell Biology and Imaging, Jagiellonian University, Kraków, Poland.
Toni CathomenFreiburg iPS Core Facility, Institute for Transfusion Medicine and Gene Therapy, Medical Center, University of Freiburg, Freiburg, Germany.
Ewa Zuba-SurmaFaculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biology, Jagiellonian University, Kraków, Poland.
Zbigniew MadejaFaculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biology, Jagiellonian University, Kraków, Poland.
Paweł E FerdekFaculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biology, Jagiellonian University, Kraków, Poland.
Sylwia Bobis-WozowiczFaculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biology, Jagiellonian University, Kraków, Poland. sylwia.bobis@uj.edu.pl.ORCID 0000-0002-2200-6767
Jagiellonian University · PLUniversity of Freiburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCardiac fibrosis is one of the top killers among fibrotic diseases and continues to be a global unaddressed health problem. The lack of effective treatment combined with the considerable socioeconomic burden highlights the urgent need for innovative therapeutic options. Here, we evaluated the anti-fibrotic properties of extracellular vesicles (EVs) derived from human induced pluripotent stem cells (hiPSCs) that were cultured under various oxygen concentrations.

methodsEVs were isolated from three hiPSC lines cultured under normoxia (21% O

resultsWe provide evidence that an oxygen concentration of 5% enhances the anti-fibrotic effects of hiPS-EVs. These EVs were more effective in reducing pro-fibrotic markers in activated human cardiac fibroblasts, when compared to EV-N or EV-H3. We show that EV-H5 act through the canonical TGFβ/SMAD pathway, primarily via miR-302b-3p, which is the most abundant miRNA in EV-H5. Our results show that EV-H5 not only target transcripts of several profibrotic genes, including SMAD2 and TGFBR2, but also reduce the stiffness of activated fibroblasts. In a mouse model of heart fibrosis, EV-H5 outperformed EV-N in suppressing the inflammatory response in the host and by attenuating collagen deposition and reducing pro-fibrotic markers in cardiac tissue.

conclusionsIn this work, we provide evidence of superior anti-fibrotic properties of EV-H5 over EV-N or EV-H3. Our study uncovers that fine regulation of oxygen concentration in the cellular environment may enhance the anti-fibrotic effects of hiPS-EVs, which has great potential to be applied for heart regeneration.

Indexed as

Extracellular VesiclesInduced Pluripotent Stem CellsMicroRNAsAnimalsDisease Models, AnimalFibrosisHumansHypoxiaMiceOxygenSmad2 ProteinTransforming Growth Factor betaMicroRNAsMIRN302A microRNA, humanOxygenSmad2 ProteinSMAD2 protein, humanTransforming Growth Factor betaExtracellular vesiclesHeart fibrosisHypoxiaInduced pluripotent stem cellsLow oxygenTherapy

Identifiers

PMID37904135
PMCPMC10617123
OpenAlexW4388033763

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.