Drug Discovery and Development

2D to 3D Cell Culture

There has been a recent shift toward using 3D cell models in drug discovery and disease modeling, as numerous studies show they better mimic the in vivo environment and provide more physiologically-relevant data than 2D models.

• Article: Making the move from 2D to 3D cell culture: an interview with Molecular Devices’ Jayne Hesley and Jeff McMillan
• Webinar: Getting started with imaging 3D cell models, A collaboration with Molecular Devices and MIMETAS
• Webinar: Transitioning high-content assays to 3D: Scientific opportunities & imaging challenges

3D Cell Imaging and Analysis

Three-dimensional (3D) cell models are physiologically relevant and more closely represent tissue microenvironments, cell-to-cell interactions, and biological processes that occur in vivo. Now you can generate more predictive data by incorporating technologies like the ImageXpress system with the integrated 3D Analysis Module in MetaXpress® software. This single interface will enable you to meet 3D acquisition and analysis challenges without compromise to throughput or data quality, giving you confidence in your discoveries.

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3D Cell Models

3D cell cultures offer the advantage of closely recapitulating aspects of human tissues including the architecture, cell organization, cell-cell and cell-matrix interactions, and more physiologically-relevant diffusion characteristics. Utilization of 3D cellular assays adds value to research and screening campaigns, spanning the translational gap between 2D cell cultures and whole-animal models. By reproducing important parameters of the in vivo environment, 3D models can provide unique insight into the behavior of stem cells and developing tissues in vitro.

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Cell Health

Cell viability refers to the number of healthy cells in a population and can be evaluated using assays that measure enzyme activity, cell membrane integrity, ATP production, and other indicators. These methods can employ luminescent, fluorescent, or colorimetric readouts as indicators of general cell viability or even specific cellular pathways. Cytotoxicity and cell viability assays are often used to assess a drug or other treatment’s effect, and are valuable tools in the search for new therapeutics, as well as advancing our understanding of how normal cells function.

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Cell Painting

Cell Painting is a high-content, multiplexed image-based assay used for cytological profiling. In a Cell Painting assay, up to six fluorescent dyes are used to label different components of the cell including the nucleus, the endoplasmic reticulum, mitochondria, cytoskeleton, the Golgi apparatus, and RNA. The goal is to “paint” as much of the cell as possible to capture a representative image of the whole cell.

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Cell Signaling

Cellular signaling allows cells to respond to their environment and communicate with other cells. Proteins located on the cell surface can receive signals from their surroundings and transmit information into the cell via a series of receptors, kinases, transcription factors, and other regulatory proteins that include signaling pathways. Multicellular organisms rely on an extensive array of signaling pathways to coordinate the proper growth, regulation, and function of cells and tissues. If signaling between or within cells is dysregulated, inappropriate cellular responses may lead to cancer and other diseases.

Many tools have been developed to measure cellular responses occurring through a wide range of signaling pathways. As an example, G protein-coupled receptor (GPCR) signaling can be studied using assays ranging from calcium flux, which can be monitored using fluorescence dyes, to changes in downstream effector molecules assessed by TR-FRET.

• Measure dual-luciferase reporter gene activity with the SpectraMax® Mini Multi-Mode Microplate Reader
• HTRF IP-One Gq assay on SpectraMax readers
• Characterization of hERG channel blockers using the FLIPR Potassium Assay Kit on the FLIPR Tetra System

Disease Modeling

Understanding the biology of human diseases is crucial to find effective treatment, and cell lines derived from cancer tissues help develop better anti-cancer drugs. However, now there is a pressing need to increase complexity and relevance of cell-based models to more accurately predict the effects of new drug candidates. Genetically engineered human or animal cells that carry disease mutation display all or some of the pathological processes observed in actual human disease. Designing 3D models that mimic tissues and cell interactions allows researchers to better predict drug effects. 3D cell models, including spheroids, organoids, and organ-on-a-chip, can be built from established cell lines derived from iPSC cells or patient derived cells. Cells can be derived from patient tissue representing rare type of cancer, or genetically modified to introduce or repair disease-related genes.

• Webinar: Establishing and imaging 3D oncology models
• Webinar: Disease modeling in the 21st century: Automated organoid assays with 3D imaging
• Publication: Disease Modeling with 3D Cell-Based Assays Using a Novel Flowchip System and High-Content Imaging
• Webinar: Capturing the complexity of 3D biology: Organoids for disease modelling and toxicity research
• Poster: Novel assay methods for cancer patient derived organoids
• Customer Breakthrough: Bioneer use the ImageXpress Micro Confocal for high-throughput imaging of 3D disease models
• Webinar: High-throughput, organoid-derived organ-on-a-chip systems for drug discovery and disease modelling

Label-free Assays

Traditional drug discovery screening assays can be detrimental to cell health and lead to interactions that can compromise data integrity. While fluorescence, luminescence, and radioactive assays can provide valuable data, there are substantial downsides as well. With advances in screening, label-free assays have been developed that do not require dyes or specialized reagents and instead can measure live cells for targets of interest in a more efficient, less disruptive way.

• Direct screening cytotoxic and antiproliferative activities of drug compounds on human leukemia U937 cell
• Label-free cell segmentation with IN Carta SINAP application module
• The diverse utility of CloneSelect Imager in label-free imaging applications
• Deep Learning-based Image Analysis for Label-free Live Monitoring of iPSC and 3D Organoid Cultures
• Novel assay methods for cancer patient derived organoids
• Quantification of spheroid growth and morphology

Stem Cell Research

Stem cells provide researchers with new opportunities to study targets and pathways that are more relevant to disease processes. They oer a more realistic model to identify and confirm new drug targets and generate pharmacology and toxicology data earlier, with stronger translation to the clinical setting. Additionally, the application of stem cells in drug development creates a new path to personalized medicine, while at the same time reducing, or even potentially replacing, animal testing.

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Toxicity

Toxicity is the measurement of the dosage needed of a chemical substance that can damage an organism. Drug-induced organ toxicity is a key factor in pharmaceutical candidates failing to make it to market. Thus, highly predictive assays for safety and efficacy testing are crucial for improving drug development and reducing drug candidate attrition.

• Lung organoids for disease modeling and toxicity assessment by 3D high-content imaging and analysis
• Toxicity assays using induced pluripotent stem cell-derived cells
• Multi-parameter imaging assay for measuring toxicity in a tumor model
• Phenotypic characterization of toxic compound effects on cardiomyocytes derived from induced pluripotent stem cells