A high-throughput three-dimensional cell migration assay for toxicity screening with mobile device-based macroscopic image analysis

Timm, David M.; Chen, Jianbo; Sing, David C.; Gage, Jacob A.; Haisler, William L.; Neeley, Shane K.; Raphael, Robert M.; Dehghani, Mehdi; Rosenblatt, Kevin P.; Killian, T. C.; Tseng, Hubert; Souza, Glauco R.

doi:10.1038/srep03000

Cited by 86 publications

(102 citation statements)

References 37 publications

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“…These types of organotypic representations of tissue for drug screening are likely to become increasingly popular with the advent of patient-derived cultures [78]. These systems can be used with a more reductionist approach as well, e.g., ECM stiffness has been reported to be a powerful mediator of drug response for paclitaxel [79], ibuprofen [80], and sorafenib [81]. Ideally, the findings demonstrated here can be related to quantifiable, predictive biomarkers, informing drug treatment and monitoring.…”

Section: Predicting Drug Response For Metastatic Patientsmentioning

confidence: 99%

The predictive link between matrix and metastasis

Barney

Jansen

Polio

et al. 2016

Current Opinion in Chemical Engineering

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Cancer spread (metastasis) is responsible for 90% of cancer-related fatalities. Informing patient treatment to prevent metastasis, or kill all cancer cells in a patient’s body before it becomes metastatic is extremely powerful. However, aggressive treatment for all non-metastatic patients is detrimental, both for quality of life concerns, and the risk of kidney or liver-related toxicity. Knowing when and where a patient has metastatic risk could revolutionize patient treatment and care. In this review, we attempt to summarize the key work of engineers and quantitative biologists in developing strategies and model systems to predict metastasis, with a particular focus on cell interactions with the extracellular matrix (ECM), as a tool to predict metastatic risk and tropism.

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Section: Predicting Drug Response For Metastatic Patientsmentioning

confidence: 99%

The predictive link between matrix and metastasis

Barney

Jansen

Polio

et al. 2016

Current Opinion in Chemical Engineering

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“…Another successful example is the magnetic nanobeads-mediated spheroid formation [41][42][43][44][45][46][47][48][49] . This method (also known as 'magnetic levitation' when the cells are collected on top of the fluid in a tissue culture well rather than on its bottom 41 ), is extremely versatile.…”

Section: Cell Spheroids As Building Blocks For Bioprintingmentioning

confidence: 99%

Principles of the Kenzan Method for Robotic Cell Spheroid-Based Three-Dimensional Bioprinting

Moldovan

Hibino

Nakayama

2017

Tissue Engineering Part B: Reviews

243

204

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Abstract.Bioprinting is a technology with the prospect to change the way many diseases are treated, by replacing the damaged tissues with live, de novo created bio-similar constructs. However, after more than a decade of incubation and many proofs-of-concept, the field is still in its infancy. The current stagnation is the consequence of its early success: the first bioprinters, and most of those which followed, were modified versions of the 3D printers used in additive manufacturing, redesigned for layer-by-layer dispersion of biomaterials. In all variants (inkjet, micro-extrusion or laser-assisted), this approach is material-('scaffold'-) dependent and energy-intensive, making it hardly compatible with some of the intended biological applications. Instead, the future of bioprinting may benefit from the use of gentler, scaffoldfree bio-assembling methods. A substantial body of evidence has accumulated indicating this is possible by use of preformed cell spheroids, which have been assembled in cartilage, bone and cardiac muscle-like constructs. However, a commercial instrument capable to directly and precisely 'print' spheroids has not been available until the invention of the microneedles-based ('Kenzan') spheroid assembling, and the launching in Japan of a bioprinter based on this method. This robotic platform laces spheroids into predesigned contiguous structures with micron-level precision, using stainless steel micro-needles ("kenzans') as temporary support. These constructs are further cultivated until the spheroids fuse into cellular aggregates and synthesize their own extracellular matrix, thus attaining the needed structural organization and robustness. This novel technology opens wide opportunities for bio-engineering of tissues and organs.

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“…monolayer scratch assay, transwell assay and EZ-TAXIScan assay) are not easily adaptable for high-throughput screening. 96-well formats can be modified and automated for microfluidic devices (Berthier et al, 2013; Guckenberger et al, 2014; Irimia and Toner, 2009; Wu et al, 2013), Boyden chambers (Hulkower and Herber, 2011; Mastyugin et al, 2004), and several image-based assays (Berthier et al, 2013; Guckenberger et al, 2014; Hattori et al, 2010; Hulkower and Herber, 2011; Kato et al, 2008; Mastyugin et al, 2004; Ponath et al, 2000; Soltaninassab et al, 2008; Timm et al, 2013; Wu et al, 2013), but they are not optimally compatible to screen ~1000 compounds. We are able screen >10,000 compounds over 5-log concentrations, for both chemotaxis and viability.…”

Section: Commentarymentioning

confidence: 99%

A Unique High‐Throughput Assay to Identify Novel Small Molecule Inhibitors of Chemotaxis and Migration

Liao

Kimmel

2017

CP Cell Biology

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Chemotaxis and cell migration play pivotal roles in normal physiological processes such as embryogenesis, inflammation, and wound healing, as well as, in pathological processes including chronic inflammatory disease and cancer metastasis. Novel chemotaxis/migration inhibitors are desirable for developing effective therapeutics and probing molecular mechanisms. We describe a fluorescence-based phenotypic assay in a 1536-well plate format for high-throughput screening of novel inhibitors of chemotaxis/migration within complex libraries of multi-1000 compounds. Although the assay utilizes the unique cellular response properties of Dictyostelium, the compounds identified are able to inhibit chemotaxis of mammalian cells. In addition, a parallel cell cytotoxicity counter-screen with an ATP content assay is described that eliminates cytotoxic compounds from the screen. This novel compound screening approach enables rapid identification of novel lead compounds that inhibit chemotaxis in human and other cells for drug development and research tools.

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A high-throughput three-dimensional cell migration assay for toxicity screening with mobile device-based macroscopic image analysis

Cited by 86 publications

References 37 publications

The predictive link between matrix and metastasis

The predictive link between matrix and metastasis

Principles of the Kenzan Method for Robotic Cell Spheroid-Based Three-Dimensional Bioprinting

A Unique High‐Throughput Assay to Identify Novel Small Molecule Inhibitors of Chemotaxis and Migration

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