A Primary Cell and Organoid Platform for Evaluating Pharmacological Responses in Mammary Epithelial Cells,ACS Pharmacology & Translational Science

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A Primary Cell and Organoid Platform for Evaluating Pharmacological Responses in Mammary Epithelial Cells
ACS Pharmacology & Translational Science ( IF 4.9 ) Pub Date : 2020-01-27 , DOI: 10.1021/acsptsci.9b00090
Teneale A Stewart _{1,

2} , Felicity M Davis _{1,

2}

Affiliation

An essential process in predicting the in vivo pharmacological activity of a candidate molecule involves the evaluation of target responses using established model systems. While these models largely comprise immortalized cells, which are often serially passaged as monolayers on uniformly stiff substrates and are modified to overexpress one or more components of the pathway-of-interest, the importance of cell identity, heterogeneity, and three-dimensional (3D) context to target response is gaining increasing attention. Here, we assess intracellular calcium responses in mouse mammary epithelial cells in three distinct model systems: 3D primary organoids, 2D primary epithelial cells, and 2D immortalized cells. Specifically, we assess intracellular calcium responses to a number of extracellular signals implicated in the regulation of basal (or myoepithelial) cell function. These findings provide further insights into cell type and context-specific pharmacological responses in mammary epithelial cells and highlight the opportunities and challenges in the adoption of architecturally complex and heterogeneous in vitro assays in pharmacological research.

中文翻译：

用于评估乳腺上皮细胞药理反应的原代细胞和类器官平台

预测候选分子体内药理活性的一个重要过程涉及使用已建立的模型系统评估目标反应。虽然这些模型主要包含永生化细胞，这些细胞通常在均匀坚硬的基质上作为单层连续传代，并经过修饰以过度表达感兴趣途径的一种或多种成分，但细胞身份、异质性和三维 (3D) 的重要性）目标响应的背景越来越受到关注。在这里，我们评估了三种不同模型系统中小鼠乳腺上皮细胞的细胞内钙反应：3D 原代类器官、2D 原代上皮细胞和 2D 永生化细胞。具体来说，我们评估细胞内钙对与基底（或肌上皮）细胞功能调节有关的许多细胞外信号的反应。这些发现提供了对乳腺上皮细胞的细胞类型和特定环境药理反应的进一步见解，并强调了在药理学研究中采用结构复杂和异质的体外测定的机遇和挑战。

更新日期：2020-01-27

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