Journal Article Ppublish
PubMed: 40168102 DOI: 10.1093/stmcls/sxaf014
Impact of pro-inflammatory cytokine preconditioning on metabolism and extracellular vesicles in feline mesenchymal stromal cells: a preliminary study.
Stem Cells 43(7)
Authors: Maria Soltero-Rivera, Boaz Arzi, Lynda Bourebaba, Krzysztof Marycz
Affiliations
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, United States.
- Veterinary Institute for Regenerative Cures, School of Veterinary Medicine, University of California-Davis, Davis, CA, United States.
- Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
Abstract
BACKGROUND
Extracellular vesicles (EVs) derived from mesenchymal stem cells have shown promise in treating inflammation. This study investigates whether preconditioning feline adipose-derived stem cells (FeASCs) with inflammatory cytokines, specifically IFN-γ and TNF-α, enhances the anti-inflammatory efficacy of MSC-derived EVs.
OBJECTIVE
We hypothesize that cytokine-primed FeASCs will produce EVs with improved anti-inflammatory properties and that this preconditioning will affect mitochondrial dynamics to enhance EV therapy effectiveness.
METHODS
FeASCs were exposed to a TNF-α/IFN-γ combination to mimic a pro-inflammatory milieu favoring ASCs' immunosuppressive phenotype. We analyzed morphological, metabolic, and immunomodulatory characteristics of native and cytokine-primed FeASCs. EVs were assessed for anti-inflammatory and mitochondrial-related markers. We also evaluated mitochondrial function and apoptosis markers in cytokine-primed cells.
RESULTS
Cytokine priming led to significant morphological changes in FeASCs, including enhanced cell projections and increased apoptosis. EVs from cytokine-primed FeASCs exhibited a heightened immunomodulatory profile, with increased expression of both pro-inflammatory and anti-inflammatory mediators. Transcriptomic analysis of these EVs revealed the upregulation of genes associated with cell proliferation, survival, and apoptosis. Mitochondrial function was impaired in cytokine-primed cells, but mitochondrial morphology remained unchanged. EVs from these cells contained higher levels of mitochondrial-related transcripts, indicating a compensatory response.
CONCLUSIONS
Cytokine-primed FeASCs generate EVs with enhanced immunomodulatory potential, highlighting their therapeutic promise. However, further research is needed to validate their efficacy and safety and refine preconditioning strategies to optimize EV-based therapies for inflammatory conditions. These advancements could pave the way for broader applications in regenerative medicine.
MeSH
Cytokines, Cells, Extracellular Vesicles, Microscopy, Electron, Scanning Transmission, Regenerative Medicine, Stem Cells, Mesenchymal Stem Cells, Therapeutics, Stromal Cells, Apoptosis