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Non-Destructive Tumor Aggregate Morphology and Viability Quantification at Cellular Resolution, During Development and in Response to Drug.

Abstract：

: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.

journal_name

Acta Biomater

journal_title

Acta biomaterialia

authors

Roberge CL,Kingsley DM,Faulkner DE,Sloat CJ,Wang L,Barroso M,Intes X,Corr DT

doi

10.1016/j.actbio.2020.09.042

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

322-334

eissn

1742-7061

issn

1878-7568

pii

S1742-7061(20)30565-1

journal_volume

117

pub_type

杂志文章

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