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Prolonged exposure to inflammatory molecules has been explored to improve their action because MSCs therapies seem to be improved transiently with such stimuli. However, the possibility of cyclically stimulating MSCs to recover their optimized therapeutic potential is still to be elucidated, although the efficacy of cell\u2010based therapies may be dependent on the ability to readapt to the relapse pathological conditions. Here, the response of MSCs, encapsulated in alginate hydrogels and cultured for 22 d, is explored using three different regimes: single, continuous, and intermittent stimulation with IFN\u03b3. Exposure to IFN\u03b3 leads to a decrease in the secretion of IL\u201010, which is cyclically countered by IFN\u03b3 weaning.\u00a0Conditioned media collected at different stages of pulsatile stimulation show an immunomodulatory potential toward macrophages, which directly correlates with IL\u201010 concentration in media. To understand whether the correlation between cyclic stimulation of MSCs and other biological actions can be observed, the effect on endothelial cells is studied, showcasing an overall modest influence on tube formation. Overall, the results describe the response of encapsulated MSCs to unusual pulsatile simulation regimens, exploring encapsulated MSCs as a living on\u2010demand release system of tailored secretomes with recoverable immunomodulatory action.<\/jats:p>","DOI":"10.1002\/adhm.202304012","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T05:44:28Z","timestamp":1711604668000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Encapsulated Mesenchymal Stromal Cells as Cyclic Providers of Immunomodulatory Secretomes: A Living on\u2010Demand Delivery System"],"prefix":"10.1002","volume":"13","author":[{"given":"Ana Rita","family":"Sousa","sequence":"first","affiliation":[{"name":"Department of Chemistry CICECO \u2013 Aveiro Institute of Materials University of Aveiro Aveiro 3810\u2010193 Portugal"}]},{"given":"Diana 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