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Role of MALDI-MSI in Combination with 3D Tissue Models for Early Stage Efficacy and Safety Testing of Drugs and Toxicants
Expert Review of Proteomics ( IF 3.4 ) Pub Date : 2021-01-13
Chloe E Spencer, Lucy E Flint, Catherine J Duckett, Laura M Cole, Neil Cross, David P Smith, Malcolm R Clench

Abstract

Introduction

Three-dimensional (3D) cell cultures have become increasingly important materials to investigate biological processes and drug efficacy and toxicity. The ability of 3D cultures to mimic the physiology of primary tissues and organs in the human body enables further insight into cellular behaviour and is hence highly desirable in early stage drug development. Analysing the spatial distribution of drug compounds and endogenous molecules provides an insight into the efficacy of a drug whilst simultaneously giving information on biological responses.

Areas Covered

In this review we will examine the main 3D cell culture systems employed and applications, which describe their integration with mass spectrometry imaging (MSI).

Expert Opinion

MSI is a powerful technique that can map a vast range of molecules simultaneously in tissues without the addition of labels that can provide insights into the efficacy and safety of a new drug. The combination of MSI and 3D cell cultures has emerged as a promising tool in early stage drug analysis. However, the most common administration route for pharmaceutical drugs is via oral delivery. The use of MSI in combination with models of the GI tract is an area that has been little explored to date, the reasons for this are discussed.



中文翻译:

MALDI-MSI在与3D组织模型结合用于药物和毒物的早期功效和安全性测试中的作用

摘要

介绍

三维(3D)细胞培养已成为研究生物学过程以及药物功效和毒性的越来越重要的材料。3D培养物模仿人体内主要组织和器官的生理功能的能力可以进一步洞察细胞行为,因此在早期药物开发中非常需要。分析药物化合物和内源性分子的空间分布,可以洞悉药物的功效,同时提供有关生物学反应的信息。

覆盖区域

在这篇综述中,我们将研究主要的3D细胞培养系统和应用,这些系统描述了它们与质谱成像(MSI)的集成。

专家意见

MSI是一项强大的技术,可以在组织中同时绘制大量分子的图谱,而无需添加可以洞察新药功效和安全性的标记物。MSI和3D细胞培养物的结合已成为早期药物分析中有希望的工具。但是,药物的最常见给药途径是口服给药。MSI与胃肠道模型结合使用是迄今为止尚未探索的领域,对此进行了讨论。

更新日期:2021-01-14
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