Evidence map›Paper›PMID 40369583›Full record

ArticleStem cell research & therapy2025

Lyophilized MSC-EVs attenuates COVID-19 pathogenesis by regulating the JAK/STAT pathway.

Nesrine Ebrahim, Hajir A Al Saihati, Zahraa Alali, Sabry Younis Mohamed Mahmoud, Ali A Rabaan, Arigue A Dessouky, Rabab F Salim, Ashraf A Shamaa, Ahmed N Abdallah, Nehal M Elsherbiny and 4 more

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Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
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4 · The record

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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

14 authors.

Nesrine Ebrahim *Department of Medical Histology and Cell Biology Faculty of Medicine, Benha University, Benha, Egypt.
Hajir A Al Saihati *Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hafr Albatin, Hafar Al-Batin, Saudi Arabia. hajirsh@uhb.edu.sa.
Zahraa AlaliDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hafr Al Batin, P.O Box 1803, 31991, Hafr Al Batin, Saudi Arabia.
Sabry Younis Mohamed MahmoudBiology Department, College of Sciences, University of Hafr Al Batin, P. O. Box 1803, 31991, Hafar Al Batin, Saudi Arabia.
Ali A RabaanMolecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, 31311, Dhahran, Saudi Arabia.
Arigue A DessoukyDepartment of Medical Histology and Cell Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Rabab F SalimDepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Benha University, Banha, Egypt.
Ashraf A ShamaaAnesthesiology & Radiology, Faculty of Vet. Men, Cairo University, P. O. Box 12211, Giza, Egypt.
Ahmed N AbdallahHormones Department, National Research Centre, Medical Research and Clinical Studies Institute, Cairo, Egypt.
Nehal M ElsherbinyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.
Gamal OthmanDepartment of Basic Medical Sciences, College of Medicine, AlMaarefa University, Diriyah, Saudi Arabia.
Abdelnaser A BadawyDepartment of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia.
Gianpiero Di LevaSchool of Life Sciences, Keele University Staffordshire, Keele, ST5 5BG, UK.
Omnia A BadrDepartment of Genetics and Genetic Engineering, Faculty of Agriculture, Benha University, Benha, Egypt. omnia.badr@fagr.bu.edu.eg.ORCID http://orcid.org/0000-0002-2318-9630

Funding

University of Hafr Al Batin Fp-A-2022-2-5-17
6 · The paper itself

Abstract

backgroundThe JAK/STAT signaling pathway plays a crucial role in the release of interferons (IFNs) and the proinflammatory response during SARS-CoV-2 infection, contributing to the cytokine storm characteristic of severe COVID-19 cases. STAT3, a key protein in this pathway, has been implicated in promoting inflammation, making its inhibition a potential therapeutic strategy to mitigate disease severity. Mesenchymal Stem Cell-derived Extracellular Vesicles (MSC-EVs), enriched with immunomodulatory and antiviral miRNAs, offer a promising therapeutic approach by modulating gene expression and regulating inflammatory responses. This study investigates the ability of Lyophilized MSC-EVs to inhibit the JAK/STAT pathway, highlighting their potential application in COVID-19 management.

methodsMale Syrian hamsters were used as an experimental model, housed under controlled laboratory conditions. SARS-CoV-2 (hCoV-19/Egypt/NRC-03/2020) was propagated in Vero E6 cells, and viral titers were determined using plaque assays. Hamsters were intranasally challenged with the virus and treated intraperitoneally with 0.5 mL of lyophilized human Wharton's jelly-derived MSC-extracellular vesicles (MSC-EVs). Histopathological evaluations were performed on lung tissues using H&E, Masson's trichrome, and immunohistochemical staining. Morphometric analyses were conducted to assess lung injury and fibrosis. Western blotting was employed to evaluate protein expression. All procedures adhered to ethical and biosafety guidelines.

resultsThe administration of MSC-EVs significantly upregulated the expression levels of miRNA-146a, miRNA-124, miRNA-155, miRNA-29b, miRNA-7, miRNA-145 and miRNA-18a compared to their levels in the COVID-19 group, suggesting a targeted release of miRNA-cargo from the MSC-EVs into the lung tissue of the animals. MSC-EVs impaired the activation of the STAT3/STAT1 signaling pathway and reduced the cytokine storm and coagulopathy associated with COVID-19.

conclusionsThese findings suggest that MSC-EVs have the potential to effectively mitigate the pathogenesis of COVID-19 by targeting the JAK/STAT signaling pathway. Further research is needed to fully understand the mechanisms underlying the therapeutic effects of MSC-EVs and their clinical application in combating the COVID-19 pandemic.

Indexed as

COVID-19Extracellular VesiclesJanus KinasesMesenchymal Stem CellsSARS-CoV-2STAT Transcription FactorsAnimalsChlorocebus aethiopsCricetinaeDisease Models, AnimalFreeze DryingHumansLungMaleMesocricetusMicroRNAsJanus KinasesMicroRNAsSTAT3 Transcription FactorSTAT Transcription FactorsCOVID-19JAK/STAT signaling pathwayMicroRNAMSCs-EVs

Identifiers

PMID40369583
PMCPMC12079845

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LicenceCC BY-NC-ND
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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.