Nanovesicles derived from iron oxide nanoparticles-incorporated mesenchymal stem cells for cardiac repair
Nanovesicles derived from iron oxide nanoparticles-incorporated mesenchymal stem cells for cardiac repair
复制标题
DOI：
10.1126/sciadv.aaz0952
复制
发表时间：
2020-04-01
期刊：
影响因子：
13.6
通讯作者：
Kim, Byung-Soo
中科院分区：
文献类型：
--
作者：
Lee, Ju-Ro;Park, Bong-Woo;Kim, Byung-Soo
由于间充质干细胞 (MSC) 治疗的植入不良和安全性问题，MSC 衍生的外泌体已成为心肌梗塞 (MI) 的替代无细胞疗法。然而，注射后外泌体从梗塞心脏中扩散出来以及低生产率限制了临床应用的潜力。在这里，我们开发了源自氧化铁纳米粒子（IONP）掺入的MSC（IONP-MSC）的外泌体模拟细胞外纳米囊泡（NV）。磁性引导显着增强了注射的 IONP-MSC 衍生 NV（IONP-NV）在梗塞心脏内的保留。此外，IONP显着增加了IONP-MSC和IONP-NV中治疗分子的水平，这可以减少外泌体生产率低的担忧。将IONP-NV注射到梗塞心脏并磁引导诱导从炎症阶段早期转变为修复阶段，减少细胞凋亡和纤维化，并增强血管生成和心脏功能恢复。这种方法可以增强 MSC 衍生的 NV 疗法的治疗效力。
Because of poor engraftment and safety concerns regarding mesenchymal stem cell (MSC) therapy, MSC-derived exosomes have emerged as an alternative cell-free therapy for myocardial infarction (MI). However, the diffusion of exosomes out of the infarcted heart following injection and the low productivity limit the potential of clinical applications. Here, we developed exosome-mimetic extracellular nanovesicles (NVs) derived from iron oxide nanoparticles (IONPs)-incorporated MSCs (IONP-MSCs). The retention of injected IONP-MSC-derived NVs (IONP-NVs) within the infarcted heart was markedly augmented by magnetic guidance. Furthermore, IONPs significantly increased the levels of therapeutic molecules in IONP-MSCs and IONP-NVs, which can reduce the concern of low exosome productivity. The injection of IONP-NVs into the infarcted heart and magnetic guidance induced an early shift from the inflammation phase to the reparative phase, reduced apoptosis and fibrosis, and enhanced angiogenesis and cardiac function recovery. This approach can enhance the therapeutic potency of an MSC-derived NV therapy.