Encapsulated Mesenchymal Stromal Cells as Cyclic Providers of Immunomodulatory Secretomes: a living on-Demand Delivery System.

The stimulation of mesenchymal stromal cells (MSCs) with inflammatory molecules is often employed to boost their therapeutic effect. Prolonged exposure to inflammatory molecules has been explored to improve their action since 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-based therapies may be dependent on the ability to readapt to the relapse pathological conditions. Here, we report the response of MSCs, encapsulated in alginate hydrogels and cultured for 22 days, using three different regimes: single, continuous, and intermittent stimulation with IFNγ. Exposure to IFNγ led to a decrease in the secretion of IL-10, which was cyclically countered by IFNγ weaning. Conditioned media collected at different stages of pulsatile stimulation showed an immunomodulatory potential towards macrophages, which directly correlated with IL-10 concentration in media. To understand whether the correlation between cyclic stimulation of MSCs and other biological actions could be observed, the effect on endothelial cells was studied, showcasing an overall modest influence on tube formation. Overall, our results describe the response of encapsulated MSCs to unusual pulsatile simulation regimens, exploring encapsulated MSCs as a living on-demand release systems of tailored secretomes with recoverable immunomodulatory action. This article is protected by copyright. All rights reserved.