Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, People's Republic of China.
Department of Cardiology, Shanghai East Hospital of Clinical Medical College, Nanjing Medical University, Nanjing, 211166, People's Republic of China.
J Nanobiotechnology. 2021 Sep 8;19(1):271. doi: 10.1186/s12951-021-01016-x.
Myocardial infarction (MI) is one of the leading causes of global death. Dendritic cell-derived exosomes (DEXs) provide us with the possibility of improving cardiac function after MI but are limited by low retention times and short-lived therapeutic effects. In this study, we developed a novel drug delivery system incorporating alginate hydrogel that continuously releases DEXs and investigated the mechanisms underlying the action of DEXs in the improvement of cardiac function after MI.
We incorporated DEXs with alginate hydrogel (DEXs-Gel) and investigated controlled released ability and rheology, and found that DEXs-Gel release DEXs in a sustainable mammer and prolonged the retention time of DEXs but had no detrimental effects on the migration in vivo. Then DEXs-Gel was applicated in the MI model mice, we found that DEXs-Gel siginificantly enhanced the therapeutic effects of DEXs with regards to improving cardiac function after MI. Flow cytometry and immunofluorescence staining revealed that DEXs significantly upregulated the infiltration of Treg cells and M2 macrophages into the border zoom after MI, and DEXs activated regulatory T (Treg) cells and shifted macrophages to reparative M2 macrophages, both in vitro and in vivo.
Our novel delivery method provides an innovative tool for enhancing the therapeutic effects of DEXs after MI. Further analysis revealed that DEXs exert effect by activating Treg cells and by modifying the polarization of macrophages.
心肌梗死（MI）是全球死亡的主要原因之一。树突状细胞衍生的外泌体（DEXs）为我们提供了改善 MI 后心功能的可能性，但由于保留时间短和治疗效果短暂而受到限制。在这项研究中，我们开发了一种新型的包含海藻酸钠水凝胶的药物输送系统，持续释放 DEXs，并研究了 DEXs 在改善 MI 后心功能中的作用机制。
我们将 DEXs 与海藻酸钠水凝胶（DEXs-Gel）结合，并研究了其控制释放能力和流变学，发现 DEXs-Gel 以可持续的方式释放 DEXs，并延长 DEXs 的保留时间，但对体内迁移没有不利影响。然后，我们将 DEXs-Gel 应用于 MI 模型小鼠，发现 DEXs-Gel 显著增强了 DEXs 改善 MI 后心功能的治疗效果。流式细胞术和免疫荧光染色显示，DEXs 显著增加了 Treg 细胞和 M2 巨噬细胞在 MI 后边界区的浸润，DEXs 在体外和体内均激活调节性 T（Treg）细胞，并将巨噬细胞转向修复性 M2 巨噬细胞。
我们的新型递送方法为增强 DEXs 在 MI 后的治疗效果提供了一种创新工具。进一步分析表明，DEXs 通过激活 Treg 细胞和改变巨噬细胞的极化来发挥作用。
