MPI/MRI bimodal imaging for non-invasive tracking of extracellular vesicles targeted to infarcted myocardium

项目摘要 干细胞衍生的细胞外囊泡（EV）在修复心肌梗死（MI）方面具有很大的前景， 迫切需要开发有效的基于EV的疗法，优选通过全身给药递送。 在这种情况下，强大的EV跟踪技术对于提供阐明损伤的新能力非常宝贵 本发明的目的是提供一种用于研究来自不同细胞来源的EV的趋向性的方法，并指导和进一步优化基于EV的疗法。的 Catalyze公司的这一提议的目标是建立一种双模成像平台技术，用于跟踪电动汽车的交付， 使用磁共振成像（MRI）和磁粒子成像（MPI）检查受损心脏。在我们 初步研究，我们开发了一种新的标记策略，用于制备高纯度，磁标记， 电动汽车，被称为磁电动汽车。由于超顺磁性氧化铁（SPIO）的磁性标记， 通过使用纳米颗粒，可以使用组合的MRI和MPI以高灵敏度检测体内全身注射的EV 和特异性。在这份Catalyze提案中，我们将进一步优化和 严格验证MPI/MRI技术，以跟踪超过初始原型的磁电动汽车 示范特别是，我们将1）优化磁标记和MPI/MRI采集， 检测磁EV和2）验证MPI/MRI在小鼠MI模型中追踪治疗性EV的能力。 这条调查线是重要的，因为它将填补知识的关键差距，如何跟踪和 改善心肌修复应用的EV，如果优化，这种新的MPI/MRI有能力满足 未满足的需求，这是一种有效的手段，调查伤害嗜性的SC-EV，从而促进 开发更有效的基于EV的心肌修复再生医学。此外，MRI具有 即时可翻译性，并将促进EV治疗在未来的临床应用，而MPI也 有翻译的潜力。拟议的研究是创新的，因为拟议的研究将使用一种新的 标记策略，其允许有效地制备高度纯化的磁性EV，以及MPI/MRI多模式 检测方法，能够以高空间分辨率定量跟踪体内磁电动汽车 方式

Project summary Stem cells derived extracellular vesicles (EV) hold great promise for repairing myocardial infarctions (MI), and there is an urgent need to develop effective EV-based therapies, preferably delivered by systemic administration. In this context, a robust EV-tracking technology is invaluable to provide the new capability to elucidate the injury tropism of EVs derived from different cell sources and to guide and further optimize EV-based therapies. The goal of this Catalyze proposal is to establish a bimodal imaging platform technology for tracking EV delivery to the injured heart using magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). In our preliminary studies, we developed a novel labeling strategy for preparing highly purified, magnetically labeled EVs, dubbed magneto-EVs. Thanks to the magnetic labeling by superparamagnetic iron oxide (SPIO) nanoparticles, one can use combined MRI and MPI to detect systemically injected EVs in vivo with high sensitivity and specificity in a high spatial resolution manner. In this Catalyze proposal, we will further optimize and rigorously validate the MPI/MRI technologies for tracking magneto-EVs beyond the initial prototype demonstration. In particular, we will 1) optimize magnetic labeling and MPI/MRI acquisition for accurately detecting magneto-EVs and 2) validate the ability of MPI/MRI to track therapeutic EVs in a mouse MI model. This line of investigation is significant because it will fill the critical gap in knowledge as to how to track and improve EV for myocardial repair applications, and this new MPI/MRI has the capability, if optimized, to meet the unmet need, that is an effective means to investigate the injury-tropism of SC-EVs and thereby promote the development of more effective, EV-based regenerative medicine for myocardial repair. Furthermore, MRI has immediate translatability and will facilitate the clinical application of EV therapies in the future, whereas MPI also has translation potential. The proposed research is innovative because the proposed study will use a novel labeling strategy, which allows preparing highly purified magneto-EVs efficiently, and an MPI/MRI multimodal detection approach, which enables quantitative tracking of magneto-EVs in vivo in a high spatial resolution manner.