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

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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.