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

MPI/MRI 双模成像，用于无创追踪梗塞心肌细胞外囊泡

• 批准号: 10557225
• 负责人: Guanshu Liu
• 金额: $ 47.93万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10557225
• 关键词: 3-Dimensional; Acceleration; Advanced Development; Animal Model; Autologous; Benchmarking; Biological Availability; Cardiac; Cardiovascular Diseases; Cause of Death; Cells; Comprehension; Detection; Development; Dilatation - action; Electroporation; Engineering; Equipment; Future; Goals; Heart; Heart Injuries; Histologic; Home; Homing; Image; Imaging technology; Impairment; Infarction; Injectable; Injections; Injury; Injury to Kidney; Investigation; Ischemia; Knowledge; Label; Magnetic Resonance Imaging; Magnetism; Measurement; Measures; Methods; Mission; Modeling; Monitor; Mus; Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardium; Nature; Particle Size; Patients; Peptides; Performance; Physiologic pulse; Play; Prediction of Response to Therapy; Procedures; Property; Public Health; Regenerative Medicine; Regenerative capacity; Reperfusion Injury; Research; Resolution; Role; Route; Sensitivity and Specificity; Signal Transduction; Site; Source; Spatial Distribution; Specificity; Speed; Surface; Technology; Therapeutic; Therapeutic Effect; Tracer; Treatment outcome; Tropism; United States; United States National Institutes of Health; Validation; bioluminescence imaging; clinical application; clinical translation; efficacy evaluation; extracellular vesicles; fluorescence imaging; functional improvement; heart function; imaging modality; imaging platform; improved; in vivo; induced pluripotent stem cell; injured; innovation; iron oxide; iron oxide nanoparticle; multimodality; myocardial infarct sizing; non-invasive imaging; novel; paracrine; particle; preclinical study; prototype; regenerative approach; repaired; research clinical testing; stem cell delivery; stem cells; success; superparamagnetism; technology platform; therapy outcome; translational potential; treatment strategy; uptake; vesicular release

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.

项目总结 干细胞来源的细胞外小泡(EV)在修复心肌梗死(MI)方面具有巨大的前景，并且 迫切需要开发有效的以EV为基础的疗法，最好是通过全身给药来提供。 在这种情况下，强大的EV跟踪技术对于提供新的能力来阐明损伤是非常宝贵的 研究来自不同细胞来源的EV的取向，并指导和进一步优化基于EV的治疗。这个 这一催化提案的目标是建立一个双峰成像平台技术，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)对受伤的心脏进行检查。在我们的 初步研究，我们开发了一种新的标记策略来制备高纯度的磁性标记 电动汽车，被称为磁力电动汽车。由于超顺磁性氧化铁(SPIO)的磁性标记 纳米粒子，可以结合核磁共振成像和MPI检测体内系统注射的EV，具有高灵敏度 和高空间分辨率的特异性。在这个催化提案中，我们将进一步优化和 严格验证MPI/MRI技术，以跟踪原始样机以外的磁电动车 游行示威。特别是，我们将1)优化磁性标记和MPI/MRI采集，以实现准确 检测磁EVS和2)验证MPI/MRI在小鼠MI模型中跟踪治疗性EVS的能力。 这条调查路线意义重大，因为它将填补关于如何跟踪和 改善用于心肌修复应用的EV，如果进行优化，这款新的MPI/MRI具有满足 未满足的需求，这是一种有效的手段来研究SC-EVS的伤害倾向，从而促进 开发更有效的、以EV为基础的心肌修复再生药物。此外，核磁共振成像已经 可即时翻译，并将促进未来EV疗法的临床应用，而MPI还 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颖的 标记策略，允许高效地制备高纯度的磁电动车，以及MPI/MRI多模式 检测方法，能够在高空间分辨率下对活体磁电动汽车进行定量跟踪 举止。