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.

项目概要 干细胞衍生的细胞外囊泡（EV）在修复心肌梗塞（MI）方面具有广阔的前景， 迫切需要开发有效的基于 EV 的疗法，最好通过全身给药来提供。 在这种情况下，强大的 EV 跟踪技术对于提供阐明损伤的新功能非常宝贵 不同细胞来源的 EV 的趋向性，并指导和进一步优化基于 EV 的疗法。这 该 Catalyze 提案的目标是建立双模成像平台技术，用于跟踪电动汽车交付至 使用磁共振成像 (MRI) 和磁粒子成像 (MPI) 来检查受伤的心脏。在我们的 初步研究中，我们开发了一种新颖的标记策略，用于制备高纯度的磁性标记 电动汽车，称为磁电动汽车。得益于超顺磁性氧化铁 (SPIO) 的磁性标记 纳米颗粒，可以结合使用 MRI 和 MPI 来高灵敏度地检测体内系统注射的 EV 和高空间分辨率方式的特异性。在本次Catalyze提案中，我们将进一步优化和 严格验证 MPI/MRI 技术，用于跟踪初始原型之外的磁电动汽车 示范。特别是，我们将 1) 优化磁性标记和 MPI/MRI 采集，以准确地 检测磁电动汽车，2) 验证 MPI/MRI 在小鼠 MI 模型中跟踪治疗电动汽车的能力。 这一研究方向意义重大，因为它将填补关于如何跟踪和记录的知识的关键空白。 改善心肌修复应用的 EV，这种新的 MPI/MRI 如果经过优化，能够满足 未满足的需求，这是研究 SC-EV 的损伤取向的有效手段，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还 即时可翻译性，将促进未来 EV 疗法的临床应用，而 MPI 也 具有翻译潜力。拟议的研究具有创新性，因为拟议的研究将使用一种新颖的方法 标记策略，可以有效地制备高度纯化的磁电动汽车，以及 MPI/MRI 多模态 检测方法，能够以高空间分辨率对磁电动汽车进行体内定量跟踪 方式。