A 3D-microtissue-based phenotypic screening of radiation resistant tumor cells with synchronized chemotherapeutic treatment

Anastasov, Nataša; Höfig, Ines; Radulović, Vanja; Ströbel, Simon; Salomon, Michael; Lichtenberg, Jan; Rothenaigner, Ina; Hadian, Kamyar; Kelm, Jens M.; Thirion, Christian; Atkinson, Michael J.

doi:10.1186/s12885-015-1481-9

Cited by 49 publications

(57 citation statements)

References 36 publications

(34 reference statements)

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“…For the generation of Hanging Drops (HDs), a cell suspension of 1,000 (FaDu) or 2,000 cells (Cal27) was used in the GravityPLUS™ 3D Culture and Assay Platform (InSphero, Schlieren, Switzerland). The platform was then incubated as described previously (34). Depending on cell line, 3 (FaDu) to 5 (Cal27) days turned out to yield the best results in terms of morphology.…”

Section: Methodsmentioning

confidence: 99%

Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer

Hagemann

Jacobi

Hahn

et al. 2017

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Section: Methodsmentioning

confidence: 99%

Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer

Hagemann

Jacobi

Hahn

et al. 2017

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“…In CellProfiler, we used a mixture of a Gaussian global threshold method and an intensity-based splitting of clumped objects with object diameters in the range [25 and 35] pixels. In the MLGOC model, the preferred radius was set empirically to 17 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Accurate Morphology Preserving Segmentation of Overlapping Cells based on Active Contours

Molnár

Jermyn

Kató

et al. 2016

Sci Rep

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The identification of fluorescently stained cell nuclei is the basis of cell detection, segmentation, and feature extraction in high content microscopy experiments. The nuclear morphology of single cells is also one of the essential indicators of phenotypic variation. However, the cells used in experiments can lose their contact inhibition, and can therefore pile up on top of each other, making the detection of single cells extremely challenging using current segmentation methods. The model we present here can detect cell nuclei and their morphology even in high-confluency cell cultures with many overlapping cell nuclei. We combine the “gas of near circles” active contour model, which favors circular shapes but allows slight variations around them, with a new data model. This captures a common property of many microscopic imaging techniques: the intensities from superposed nuclei are additive, so that two overlapping nuclei, for example, have a total intensity that is approximately double the intensity of a single nucleus. We demonstrate the power of our method on microscopic images of cells, comparing the results with those obtained from a widely used approach, and with manual image segmentations by experts.

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“…3D microtissues were produced within 3 days and transferred into InSphero GravityTRAP ™ plates. Growth of six spheroids per approach was analyzed every 3 days by the high content screening system Operetta (Perkin Elmer, Waltham, MA) and quantified in maximal area of GFP‐expressing microtissue ( μ m 2 ) using the Harmony analysis Software (Perkin Elmer) . Medium was refreshed at day 6 posttransfer to assay plates.…”

Section: Methodsmentioning

confidence: 99%

Three‐dimensional microtissues essentially contribute to preclinical validations of therapeutic targets in breast cancer

et al. 2016

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A 3D microtissues using T47D and JIMT‐1 cells were generated to analyze tissue‐like response of breast cancer cells after combined human epidermal growth factor receptor 2 (HER2)‐targeted treatment and radiation. Following lentiviral knockdown of HER2, we compared growth rate alterations using 2D monolayers, 3D microtissues, and mouse xenografts. Additionally, to model combined therapeutic strategies, we treated HER2‐depleted T47D cells and 3D microtissues using trastuzumab (anti‐HER2 antibody) in combination with irradiation. Comparison of HER2 knockdown with corresponding controls revealed growth impairment due to HER2 knockdown in T47D 2D monolayers, 3D microtissues, and xenografts (after 2, 12, and ≥40 days, respectively). In contrast, HER2 knockdown was less effective in inhibiting growth of trastuzumab‐resistant JIMT‐1 cells in vitro and in vivo. Combined administration of trastuzumab and radiation treatment was also analyzed using T47D 3D microtissues. Administration of both, radiation (5 Gy) and trastuzumab, significantly enhanced the growth inhibiting effect in 3D microtissues. To improve the predictive power of potential drugs—as single agents or in combination—here, we show that regarding tumor growth analyses, 3D microtissues are highly comparable to outcomes derived from xenografts. Considering increased limitations for animal experiments on the one hand and strong need of novel drugs on the other hand, it is indispensable to include highly reproducible 3D microtissue platform in preclinical analyses to validate more accurately the capacity of future drug‐combined radiotherapy.

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A 3D-microtissue-based phenotypic screening of radiation resistant tumor cells with synchronized chemotherapeutic treatment

Cited by 49 publications

References 36 publications

Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer

Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer

Accurate Morphology Preserving Segmentation of Overlapping Cells based on Active Contours

Three‐dimensional microtissues essentially contribute to preclinical validations of therapeutic targets in breast cancer

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