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MS imaging of multicellular tumor spheroids and organoids as an emerging tool for personalized medicine and drug discovery.
Journal of Biological Chemistry ( IF 4.0 ) Pub Date : 2021-08-28 , DOI: 10.1016/j.jbc.2021.101139
Yijia Wang 1 , Amanda B Hummon 1
Affiliation  

MS imaging (MSI) is a powerful tool in drug discovery because of its ability to interrogate a wide range of endogenous and exogenous molecules in a broad variety of samples. The impressive versatility of the approach, where almost any ionizable biomolecule can be analyzed, including peptides, proteins, lipids, carbohydrates, and nucleic acids, has been applied to numerous types of complex biological samples. While originally demonstrated with harvested organs from animal models and biopsies from humans, these models are time consuming and expensive, which makes it necessary to extend the approach to 3D cell culture systems. These systems, which include spheroid models, prepared from immortalized cell lines, and organoid cultures, grown from patient biopsies, can provide insight on the intersection of molecular information on a spatial scale. In particular, the investigation of drug compounds, their metabolism, and the subsequent distribution of their metabolites in 3D cell culture systems by MSI has been a promising area of study. This review summarizes the different ionization methods, sample preparation steps, and data analysis methods of MSI and focuses on several of the latest applications of MALDI-MSI for drug studies in spheroids and organoids. Finally, the application of this approach in patient-derived organoids to evaluate personalized medicine options is discussed.

中文翻译:

多细胞肿瘤球体和类器官的 MS 成像作为个性化医学和药物发现的新兴工具。

MS 成像 (MSI) 是一种强大的药物发现工具,因为它能够检测各种样品中的各种内源性和外源性分子。该方法令人印象深刻的多功能性,几乎可以分析任何可电离的生物分子,包括肽、蛋白质、脂质、碳水化合物和核酸,已应用于多种类型的复杂生物样品。虽然最初是用从动物模型中获取的器官和来自人类的活检进行展示,但这些模型既耗时又昂贵,因此有必要将这种方法扩展到 3D 细胞培养系统。这些系统包括从永生化细胞系制备的球体模型和从患者活检中培养的类器官培养物,可以提供对空间尺度上分子信息交叉点的洞察。特别是,MSI 对药物化合物、它们的代谢及其代谢物在 3D 细胞培养系统中的后续分布的研究一直是一个很有前景的研究领域。本综述总结了 MSI 的不同电离方法、样品制备步骤和数据分析方法,并重点介绍了 MALDI-MSI 在球体和类器官药物研究中的几个最新应用。最后,讨论了这种方法在来自患者的类器官中的应用,以评估个性化医疗选择。和 MSI 的数据分析方法,重点介绍 MALDI-MSI 在球体和类器官药物研究中的几个最新应用。最后,讨论了这种方法在来自患者的类器官中的应用,以评估个性化医疗选择。和 MSI 的数据分析方法,重点介绍 MALDI-MSI 在球体和类器官药物研究中的几个最新应用。最后,讨论了这种方法在来自患者的类器官中的应用,以评估个性化医疗选择。
更新日期:2021-08-27
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