Development of an Imaging Mass Spectrometry Technique for Visualizing Localized Cellular Signaling Mediators in Tissues.
Development of an Imaging Mass Spectrometry Technique for Visualizing Localized Cellular Signaling Mediators in Tissues.
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DOI：
10.5702/massspectrometry.a0040
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Suematsu, Makoto
中科院分区：
文献类型：
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作者：
Sugiura, Yuki;Honda, Kurara;Suematsu, Makoto
细胞信号传导介质（例如炎症介质）的体内浓度通常维持在非常低的水平，因为它们具有很强的诱导生物反应的能力。这些介质的产生、扩散和分解是受时空调控的。因此，为了了解疾病进展的生化基础并开发新的治疗策略，了解体内信号传导介质在疾病（例如慢性炎症性疾病）进展过程中的时空动态非常重要；然而，缺乏有效的成像技术使得很难确定它们在体内的定位。这种表征需要技术突破，包括足够灵敏的分子成像方法，能够检测患病器官异质组织区域中低水平的代谢物。我们和其他团队试图通过开发高灵敏度成像质谱（IMS）技术来填补这一技术空白。迄今为止，我们已经为实现这一目标建立了两项关键技术，包括（i）样品制备程序，消除了不稳定代谢物死后降解的问题，以及（ii）代谢物的组织衍生化，可以提高分析物电离效率。在此，我们回顾了这些技术开发的最新进展，以及高灵敏度 IMS 技术如何有助于加深对疾病机制的生化基础的了解、发现新的诊断标记物以及开发新疗法。
In vivo concentrations of cellular signaling mediators such as inflammatory mediators are normally maintained at very low levels due to their strong ability to induce a biological response. The production, diffusion, and decomposition of such mediators are spatio-temporally regulated. Therefore, in order to understand biochemical basis of disease progression and develop new therapeutic strategies, it is important to understand the spatiotemporal dynamics of the signaling mediators in vivo, during the progression of disorders, e.g., chronic inflammatory diseases; however, the lack of effective imaging technology has made it difficult to determine their localizations in vivo. Such characterization requires technical breakthroughs, including molecular imaging methods that are sensitive enough to detect low levels of metabolites in the heterogeneous tissue regions in diseased organs. We and other groups have attempted to fill this technical gap by developing highly sensitive imaging mass spectrometry (IMS) technologies. To date, we have established two key techniques toward this goal, including (i) a sample preparation procedure that has eliminated the problem of the postmortem degradation of labile metabolites, and (ii) on-tissue derivatization of metabolites, which can enhance analyte ionization efficiency. Here, we review recent progress in the development of these technologies as well as how the highly sensitive IMS technique has contributed to increasing understanding of the biochemical basis of disease mechanisms, discovery of new diagnostic markers, and development of new therapies.