![]() Typically, cancer cells are seeded in the extracellular matrix in each microtiterplate well, and over time multiple spheroids of different sizes develop. Īn important category of such models are spheroid microtumors grown in a matrix, such as Matrigel ®, with or without the presence of supporting stromal cells. The PREDECT consortium aims to validate various 3D cell culture models by comparing their histology and protein expression with that found in patient samples. Studies have demonstrated important differences in transcription profiles and drug sensitivity between 2D and 3D cell culture systems. In comparison, 3D cultures are thought to more closely mimic the tumor microenvironment, as they allow more complex interactions between cancer and stromal cells, and expose cells to more realistic mechanic forces. These models are very different from solid tumor behavior in vivo. The traditional models used for oncology drug testing are monolayer cultures of tumor cells grown on glass and plastic substrates. The authors confirm that this does not alter their adherence to all the PLOS ONE policies on sharing data and materials.ĭrug discovery and development in oncology has a success rate as low as 6%. The specific roles of these authors are articulated in the “author contributions” section.Ĭompeting interests: The authors of this manuscript have the following competing interests: MB, SJ, FC, RH, RG, EG, and YTC were employees of Janssen Pharmaceutical Companies of Johnson & Johnson. The funders provided support in the form of salaries for the authors, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Authors SV and KG were supported by Innovative Medicines Initiative Joint Undertaking under Grant agreement n° 115188, the resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and contributions in kind from the European Federation of Pharmaceutical Industries and Associations. The described files Data_3, Data_4, Data_5 and Data_6 are available from the Dryad data repository (doi: 10.5061/dryad.0m9n7).įunding: Authors MB, SJ, FC, RH, RG, EG, and YTC were funded by Janssen Pharmaceutical Companies of Johnson & Johnson. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: S1 File is available as supporting information. Received: SeptemAccepted: Published: June 15, 2016Ĭopyright: © 2016 Barbier et al. PLoS ONE 11(6):Įditor: Thomas Abraham, Pennsylvania State Hershey College of Medicine, UNITED STATES (2016) Ellipsoid Segmentation Model for Analyzing Light-Attenuated 3D Confocal Image Stacks of Fluorescent Multi-Cellular Spheroids. It alerts the user when potential bias-introducing factors cannot be compensated for and includes a compensation for signal attenuation.Ĭitation: Barbier M, Jaensch S, Cornelissen F, Vidic S, Gjerde K, de Hoogt R, et al. They are identified from information present in the Maximum Intensity Projection (MIP) and the corresponding height view, also known as Z-buffer. The spheroids are assumed to be approximately ellipsoid in shape. We present a robust, computationally inexpensive 2.5D method for the segmentation of spheroid cultures and for counting proliferating cells within them. And quantitative analysis of large 3D image data sets is challenging, creating a need for methods which can be applied to large-scale experiments and account for impeding factors. In particular, signal attenuation within the tissue of the spheroids prevents the acquisition of a complete image for spheroids over 100 micrometers in diameter. However, several issues hamper accurate analysis. If suitable fluorescent labels are applied, confocal 3D image stacks can characterize the structure of such volumetric cultures and, for example, cell proliferation. ![]() ![]() Therefore they are increasingly complemented by more physiologically relevant 3D models, such as spheroid micro-tumor cultures. In oncology, two-dimensional in-vitro culture models are the standard test beds for the discovery and development of cancer treatments, but in the last decades, evidence emerged that such models have low predictive value for clinical efficacy.
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