MONITORING STEM CELL GRAFTS USING A NOVEL MRI REPORTER

使用新型 MRI 报告仪监测干细胞移植物

• 批准号: 8357544
• 负责人: ANTHONY WING SANG CHAN
• 金额: $ 2.06万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357544
• 关键词: Adverse effects; Bacteria; Cell Line; Cells; Contrast Media; Development; Disease; Funding; Future; Gene Expression Profiling; Grant; Iron; Magnetic Resonance Imaging; Mammalian Cell; Monitor; Mus; National Center for Research Resources; Primates; Principal Investigator; Property; Relaxation; Reporter; Reporter Genes; Research; Research Infrastructure; Resolution; Resources; Signal Transduction; Source; Stem cells; System; Technology; Time; Tissues; United States National Institutes of Health; Water; base; clinical Diagnosis; cost; embryonic stem cell; in vivo; magnetite ferrosoferric oxide; magnetosomes; novel; particle

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We have proposed to develop a novel MRI reporter gene system that uses MRI to monitor gene expression and the status of cell grafts in vivo. Current MRI technology is capable of high spatial resolution at 10-mm range and has found wide applications in research as well as in the clinical diagnosis of various diseases. In vivo monitoring of cell grafts is a critical function for the future development of cell replacement based therapy. Although applications of MRI in cell tracking and monitoring have shown great promise, technical challenges have also been recognized. As cell grafts are not expected to differ in water content from surrounding tissues, they alone do not generate signals detected by MRI. MagA regulates the transport of iron and the formation of magnetite (Fe3O4) crystals in certain types of bacteria. Magnetite is a supermagnetic particle that can induce the substantial changes in water relaxation times and is therefore considered an excellent MRI contrast agent. Our lab has successfully expressed MagA in mammalian cell lines and confirmed the formation of magnetosomes, which can be readily detected in MRI. We hypothesize that MagA could be expressed in mouse embryonic stem cells (mESCs) without an adverse effect on the stem cell properties that allow an mESC graft to be monitored noninvasively by MRI. We propose to evaluate the potential of MagA as an MRI reporter gene for cell graft monitoring in vivo, one of the major barriers in advancing cell replacement research.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们已经提出开发一种新的MRI报告基因系统，使用MRI监测基因表达和细胞移植物在体内的状态。 目前的MRI技术能够在10 mm范围内实现高空间分辨率，并在各种疾病的研究和临床诊断中获得了广泛的应用。细胞移植物的体内监测是基于细胞替代疗法的未来发展的关键功能。虽然MRI在细胞跟踪和监测中的应用已经显示出巨大的前景，但技术挑战也已被认识到。由于预期细胞移植物的含水量与周围组织的含水量没有差异，因此它们本身不会产生MRI检测到的信号。MagA调节铁的运输和某些类型细菌中磁铁矿（Fe 3 O 4）晶体的形成。磁铁矿是一种超磁性颗粒，可以引起水弛豫时间的实质性变化，因此被认为是一种优秀的MRI造影剂。我们的实验室已经成功地在哺乳动物细胞系中表达了MagA，并证实了磁小体的形成，磁小体可以很容易地在MRI中检测到。我们假设MagA可以在小鼠胚胎干细胞（mESC）中表达，而不会对干细胞特性产生不良影响，从而可以通过MRI非侵入性地监测mESC移植物。我们建议评估MagA作为MRI报告基因用于体内细胞移植监测的潜力，这是推进细胞替代研究的主要障碍之一。