Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Aveiro, 3810-193, Portugal.
Adv Healthc Mater. 2024 Jul;13(17):e2304012. doi: 10.1002/adhm.202304012. Epub 2024 Apr 7.
The stimulation of mesenchymal stromal cells (MSCs) with inflammatory molecules is often used to boost their therapeutic effect. 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-based 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 IFNγ. Exposure to IFNγ leads to a decrease in the secretion of IL-10, which is cyclically countered by IFNγ weaning. Conditioned media collected at different stages of pulsatile stimulation show an immunomodulatory potential toward macrophages, which directly correlates with IL-10 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-demand release system of tailored secretomes with recoverable immunomodulatory action.
间充质基质细胞（MSCs）受到炎症分子的刺激通常用于增强其治疗效果。为了改善其作用，人们探索了长时间暴露于炎症分子的方法，因为此类刺激似乎可以使 MSCs 疗法暂时得到改善。然而，循环刺激 MSCs 以恢复其最佳治疗潜能的可能性仍有待阐明，尽管基于细胞的治疗的疗效可能取决于其适应复发病理条件的能力。在这里，研究了在藻酸盐水凝胶中包封并培养 22 天的 MSCs 对三种不同刺激方案（IFNγ 单次、持续和间歇刺激）的反应：IFNγ 刺激导致 IL-10 的分泌减少，而 IL-10 的分泌又通过 IFNγ 逐渐减少来对抗。在脉冲刺激的不同阶段收集的条件培养基显示出对巨噬细胞的免疫调节潜力，这与培养基中 IL-10 的浓度直接相关。为了了解 MSC 的循环刺激与其他生物学作用之间的相关性是否可以观察到，研究了对内皮细胞的影响，结果表明对管形成的整体影响不大。总之，这些结果描述了包封 MSCs 对异常脉冲模拟方案的反应，探索了包封 MSCs 作为定制分泌组的按需按需释放系统，具有可恢复的免疫调节作用。
