{"doi":"10.1093/stmcls/sxaf014","title":"Impact of pro-inflammatory cytokine preconditioning on metabolism and extracellular vesicles in feline mesenchymal stromal cells: a preliminary study","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.","journal":"Stem Cells","year":2025,"id":539142,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9646,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":418685,"name":"Boaz Arzi","orcid":"0000-0002-7289-8994","position":1,"is_corresponding":false},{"id":1425920,"name":"Lynda Bourebaba","orcid":"0000-0003-0660-8706","position":2,"is_corresponding":false},{"id":311083,"name":"Krzysztof Marycz","orcid":"0000-0003-3676-796X","position":3,"is_corresponding":false},{"id":1065188,"name":"Maria Soltero‐Rivera","orcid":null,"position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T02:52:25.799399Z","pmid":"40168102","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}