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一种细菌基因mms6,作为用于哺乳动物细胞磁共振成像的新型报告基因。

A bacterial gene, mms6, as a new reporter gene for magnetic resonance imaging of mammalian cells.

作者信息

Zhang Xiao-Yong, Robledo Brenda N, Harris Steven S, Hu Xiaoping P

出版信息

Mol Imaging. 2014;13. doi: 10.2310/7290.2014.00046.

Abstract

Magnetic resonance imaging (MRI) allows for noninvasive, deep tissue imaging with high spatial resolution, making it an attractive modality for in vivo cellular imaging. Since reporter genes can generate magnetic resonance (MR) contrast based on molecular activity, they offer a potentially powerful tool for cellular imaging. The mms6 gene was originally identified in magnetotactic bacteria (MTB), which is known to play a key role in magnetic crystal formation. The purpose of the present work was to investigate the possibility of using mms6 as an MR reporter gene. We established a transgenic mammalian cell line that stably expresses mms6. In vitro experiments show that mms6-expressing cells form clusters of nanoparticles within and outside membrane-enclosed structures and produce changes in MR contrast, most likely by increasing iron uptake of intracellular iron. Additionally, in vivo MRI experiments demonstrate that mms6-expressing tumors can be distinguished from parental tumors not expressing mms6, even in the absence of exogenous iron supplementation. Our results demonstrate that mms6 can function as an MR reporter gene with the potential to monitor gene expression and to visualize the proliferation, migration, and metastasis of tumor cells expressing it.

摘要

磁共振成像(MRI)能够实现具有高空间分辨率的非侵入性深部组织成像,使其成为体内细胞成像的一种有吸引力的方式。由于报告基因可以基于分子活性产生磁共振(MR)对比,它们为细胞成像提供了一种潜在的强大工具。mms6基因最初是在趋磁细菌(MTB)中发现的,已知其在磁晶体形成中起关键作用。本研究的目的是探讨使用mms6作为MR报告基因的可能性。我们建立了一个稳定表达mms6的转基因哺乳动物细胞系。体外实验表明,表达mms6的细胞在膜封闭结构内外形成纳米颗粒簇,并产生MR对比变化,最有可能是通过增加细胞内铁的摄取。此外,体内MRI实验表明,即使在不补充外源铁的情况下,表达mms6的肿瘤也可以与不表达mms6的亲本肿瘤区分开来。我们的结果表明,mms6可以作为一种MR报告基因,具有监测基因表达以及可视化表达它的肿瘤细胞的增殖、迁移和转移的潜力。

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