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Investigation of gene expression changes in normal human dermal fibroblasts after exposure to bone marrow mesenchymal stromal cell secretome

ABSTRACT: Mesenchymal stromal cells (MSCs) are been widely investigated in clinical trials for several clinical conditions. It is known that these cells do not promote their effects by engrafment and differentiation, as they die shortly after intravenous administration. Extracellular vesicles (EVs) are membrane bound particles that carry bioactive lipids, peptides and nucleic acids and act in cell-cell communication. The aim of this study is to determine the transcriptomic effects of exposure of dermal fibroblasts to fractions of bone marrow MSCs, including conditioned medium (CM), non-small extracellular vesicles (NsEV), small extracellular vesicles (sEVs) and depleted medium (DM). Differential gene expression and gene ontology analysis showed that there enrichment of pathways related to migration and genes within the regulation of cell population proliferation pathway had their expression changed after exposure to MSC-sEVs. This indicates that MSC secretome promotes targeted gene expression change that can be of particular interest in wound healing studies and clinical trials.

ORGANISM(S): Homo sapiens

PROVIDER: GSE251807 | GEO | 2025/06/16

REPOSITORIES: GEO

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Project description:BACKGROUND: Ischemia/reperfusion injury (IRI) is the leading cause of acute kidney injury (AKI). The current standard of care focuses on supporting kidney function, stating the need for more efficient and targeted therapies to enhance repair. Mesenchymal Stromal Cells (MSCs) and their secretome, either as conditioned medium (CM) or extracellular vesicles (EVs), have emerged as promising options for regenerative therapy, however, their full potential in treating AKI remains unknown.METHODS: In this study, we employed an in vitro model of chemically-induced ischemia using antimycin A combined with 2-deoxy-D-glucose to induce ischemic injury in proximal tubule epithelial cells. Afterwards, we evaluated the effects of MSC secretome, CM or EVs obtained from adipose tissue, bone marrow and umbilical cord, on ameliorating the detrimental effects of ischemia. To assess the damage and treatment outcomes, we analyzed cell morphology, mitochondrial health parameters (mitochondrial activity, ATP production, mass and membrane potential) and overall cell metabolism by metabolomics.RESULTS: Our findings show that ischemic injury caused cytoskeletal changes confirmed by disruption of the F-actin network, energetic imbalance as revealed by a 50% decrease in the oxygen consumption rate, increased oxidative stress, mitochondrial dysfunction and reduced cell metabolism. Upon treatment with MSC secretome, the morphological derangements were partly restored and ATP production increased by 40-50%, with umbilical cord-derived EVs being most effective. Furthermore, MSC treatment led to phenotype restoration as indicated by an increase in cell bioenergetics, including increased levels of glycolysis intermediates, as well as an accumulation of antioxidant metabolites.CONCLUSION: Our in vitro model effectively replicated the in vivo-like morphological and molecular changes observed during ischemic injury. Additionally, treatment with MSC secretome ameliorated proximal tubule damage, highlighting its potential as a viable therapeutic option for targeting AKI.

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Investigation of gene expression changes in normal human dermal fibroblasts after exposure to bone marrow mesenchymal stromal cell secretome

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