Language

English

Publication Date

3-28-2025

Journal

Stem Cell Research & Therapy

DOI

10.1186/s13287-025-04262-0

PMID

40156072

PMCID

PMC11951844

PubMedCentral® Posted Date

3-28-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Several immunosuppressive therapies have been proposed as key treatment options for critically ill patients since the first appearance of severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) from different sources have been considered for their potential to attenuate the cytokine storm associated to COVID-19 and the consequent multi-organ failure, providing evidence for safe and efficacious treatments. Among them, administration of umbilical cord-derived MSCs (UC-MSCs) has demonstrated a significant increase in survival rates, largely due to their potent immunosuppressive properties.

Methods: We applied next-generation sequencing (NGS) analysis to compare the transcriptomic profiles of MSCs isolated from two gestational sources: amniotic fluid (AF) obtained during prenatal diagnosis and their clinically relevant umbilical cord counterparts, for which datasets were publicly available. A full meta-analysis was performed to identify suitable GEO and NGS datasets for comparison between AF- and UC-MSC samples.

Results: Transcriptome analysis revelaed significant differences between groups, despite both cell lines being strongly involved in the tissue development, crucial to achieve the complex task of wound healing. Significantly enriched hallmark genes suggest AF-MSC superior immunomodulatory features against signaling pathways actively involved in the cytokine storm (i.e., IL-2/STAT, TNF-a/NFkB, IL-2/STAT5, PI3K/AKT/mTOR).

Conclusions: The data presented here suggest that AF-MSCs hold significant promise for treating not only COVID-19-associated cytokine storms but also a variety of other inflammatory syndromes (i.e., those induced by bacterial infections, autoimmune disorders, and therapeutic interventions). Realizing the full potential of AF-MSCs as a comprehensive therapeutic approach in inflammatory disease management will require more extensive clinical trials and in-depth mechanistic studies.

Keywords

Humans, Amniotic Fluid, Mesenchymal Stem Cells, Umbilical Cord, COVID-19, Cytokine Release Syndrome, SARS-CoV-2, Female, Mesenchymal Stem Cell Transplantation, Pregnancy, Cytokines, Transcriptome, Signal Transduction, Mesenchymal stem cells, Amniotic fluid, Umbilical cord, Cytokine storm, Transcriptomic analysis, Regulatory moieties, Immunosuppression, GSEA, COVID-19

Published Open-Access

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