Non-Destructive Tumor Aggregate Morphology and Viability Quantification at Cellular Resolution, During Development and in Response to Drug.
Non-Destructive Tumor Aggregate Morphology and Viability Quantification at Cellular Resolution, During Development and in Response to Drug.
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DOI：
10.1016/j.actbio.2020.09.042
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发表时间：
2020-11
影响因子：
9.7
通讯作者：
Corr DT
中科院分区：
文献类型：
--
作者：
Roberge CL;Kingsley DM;Faulkner DE;Sloat CJ;Wang L;Barroso M;Intes X;Corr DT
三维（3D）组织工程体外模型，特别是多细胞球体和类器官，已成为探索疾病进展和指导新治疗策略开发的重要工具。这些无血管结构在肿瘤学研究中特别强大，因为它们能够模拟体内肿瘤的几个关键方面，例如3D结构和病理生理梯度。球体模型的进步需要表征关键特征（即，大小、形状、细胞密度和存活力）以及对治疗的反应。然而，这些特征的纵向，定量和非侵入性的评价仍然是一个挑战。在本文中，光学相干断层扫描（OCT）被用作无标记工具，以评估通过液体覆盖技术生成的肿瘤球体的3D形态和细胞密度。我们利用这种定量工具来评估基质胶对球体形态发育的影响，发现基质胶的缺乏产生扁平的盘状聚集体，而不是具有生理相关特征的3D球体。此外，该技术适用于量化肿瘤球体内的细胞数量，并区分活细胞和死细胞，以非破坏性地提供关于组织/构建体活力的有价值的信息，以及纵向药物功效研究的概念验证。总之，这些发现表明OCT是一种有前途的非侵入性，定量，无标记，纵向和基于细胞的方法，可以在介观尺度上评估3D细胞聚集体的发育和药物反应。
Three-dimensional (3D) tissue-engineered in vitro models, particularly multicellular spheroids and organoids, have become important tools to explore disease progression and guide the development of novel therapeutic strategies. These avascular constructs are particularly powerful in oncological research due to their ability to mimic several key aspects of in vivo tumors, such as 3D structure and pathophysiologic gradients. Advancement of spheroid models requires characterization of critical features (i.e., size, shape, cellular density, and viability) during model development, and in response to treatment. However, evaluation of these characteristics longitudinally, quantitatively and non-invasively remains a challenge. Herein, Optical Coherence Tomography (OCT) is used as a label-free tool to assess 3D morphologies and cellular densities of tumor spheroids, generated via the liquid overlay technique. We utilize this quantitative tool to assess Matrigel’s influence on spheroid morphologic development, finding that the absence of Matrigel produces flattened, disk-like aggregates rather than 3D spheroids with physiologically-relevant features. Furthermore, this technology is adapted to quantify cell number within tumor spheroids, and to discern between live and dead cells, to non-destructively provide valuable information on tissue/construct viability, as well as a proof-of-concept for longitudinal drug efficacy studies. Together, these findings demonstrate OCT as a promising noninvasive, quantitative, label-free, longitudinal and cell-based method that can assess development and drug response in 3D cellular aggregates at a mesoscopic scale.
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影响因子：
3.3
作者：
Giavarina D
通讯作者：
Giavarina D
影响因子：
2.4
作者：
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Przyborski S
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影响因子：
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作者：
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影响因子：
3.4
作者：
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通讯作者：
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