Russell H. Morgan Department of Radiology Johns Hopkins University School of Medicine Baltimore Maryland USA.
F.M. Kirby Research Center Kennedy Krieger Institute Baltimore Maryland USA.
J Extracell Vesicles. 2021 Jan;10(3):e12054. doi: 10.1002/jev2.12054. Epub 2021 Jan 15.
Human stem-cell-derived extracellular vesicles (EVs) are currently being investigated for cell-free therapy in regenerative medicine applications, but the lack of noninvasive imaging methods to track EV homing and uptake in injured tissues has limited the refinement and optimization of the approach. Here, we developed a new labelling strategy to prepare magnetic EVs (magneto-EVs) allowing sensitive yet specific MRI tracking of systemically injected therapeutic EVs. This new labelling strategy relies on the use of 'sticky' magnetic particles, namely superparamagnetic iron oxide (SPIO) nanoparticles coated with polyhistidine tags, to efficiently separate magneto-EVs from unencapsulated SPIO particles. Using this method, we prepared pluripotent stem cell (iPSC)-derived magneto-EVs and subsequently used MRI to track their homing in different animal models of kidney injury and myocardial ischemia. Our results showed that iPSC-derived EVs preferentially accumulated in the injury sites and conferred substantial protection. Our study paves a new pathway for preparing highly purified magnetic EVs and tracking them using MRI towards optimized, systemically administered EV-based cell-free therapies.
人源干细胞衍生的细胞外囊泡（EVs）目前正在再生医学应用的无细胞治疗中进行研究，但缺乏非侵入性成像方法来跟踪损伤组织中 EV 的归巢和摄取，这限制了该方法的改进和优化。在这里，我们开发了一种新的标记策略来制备磁性 EVs（磁 EVs），从而可以通过敏感而特异的 MRI 跟踪系统注射的治疗性 EV。这种新的标记策略依赖于使用“粘性”磁性颗粒，即超顺磁氧化铁（SPIO）纳米颗粒，其表面覆盖组氨酸标签，以有效地将磁 EV 与未封装的 SPIO 颗粒分离。使用这种方法，我们制备了多能干细胞（iPSC）衍生的磁 EVs，随后使用 MRI 跟踪它们在不同的肾损伤和心肌缺血动物模型中的归巢。我们的结果表明，iPSC 衍生的 EVs 优先聚集在损伤部位，并提供了实质性的保护。我们的研究为制备高度纯化的磁性 EVs 并使用 MRI 进行跟踪开辟了一条新途径，从而实现了优化的、系统给药的基于 EV 的无细胞治疗。
