3D Cell Models

Acquire and Visualize 3D Cell Models

There has been significant progress in the development of 3D models and techniques during the last few years. Methods include biodegradable scaffolds, organ-on-a chip structures, or self-assembled organoids. Recently, simple, automated workflows, suitable for high-content imaging have become popular.

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Capture True 3D Cell Culture Insights

Developing more complex, biologically relevant, and predictive cell-based assays for compound screening is a primary challenge in drug discovery.

This ebook highlights the 3D cell culture imaging and analysis advantage and includes a few 3D cell model applications as well as tips and techniques for optimizing your 3D assay workflow.

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Cells in Extra-Cellular Matrices

One common way of culturing cells in three dimensional space is through the use of extracellular matrix-based hydrogels, such as Matrigel. Cells are grown in an extracellular matrix (ECM) to mimic an in vivo environment. Differences between Matrigel and 2D cell cultures can be readily seen by their different cell morphologies, cell polarity, and/or gene expression. Hydrogels can also enable studies on cell migration and 3D structure formation, such as endothelial cell tube formation in angiogenesis studies.

• Automating the generation and analysis of 3D cell cultures in Matrigel
• 3D analysis and morphometric characterization of compound effects on cancer spheroid cultures

Organ-on-a-Chip

Emulating organ physiology by co-culturing cells in a supportive 3D matrix and using microfluidic channels to perfuse nutrients or compounds over the resulting cellular structures, is rapidly gaining popularity as a biologically relevant screening model for new drugs or toxicity. The ImageXpress system provides a turnkey solution for both 2D or 3D applications and can accommodate many different types of slide and plate formats.

• High-content assay for morphological characterization of 3D neuronal networks in a microfluidic platform
• Physiologically-Relevant Tissue Models Using a High-Throughput Organ-on-a-Chip Platform
• Webinar: Developing high-throughput organ-on-a-chip tissue models for drug discovery using high-content imaging
• Poster: Water immersion objectives for automated high-content imaging to improve precision and quality of complex biological assays

Organoid vs. Spheroid

The terms, spheroid and organoid, are often used interchangeably. Both cell models are 3D multi-cellular structures that better mimic the in vivo environment as compared to their 2D cell counterparts. Organoids typically consist of a co-culture of cells which demonstrate a higher order of self-assembly to allow for an even better representation of complex in vivo cell responses and interactions. In contrast, spheroids have a more simplified 3D structure making them amenable to high reproducibility and scaling. Functionally, both model types are used as better in vitro models for capturing more physiologically relevant data.

Spheroids

Spheroids are multi-cellular 3D spheres which mimic in vivo cell responses and interactions. They have the ability to be highly reproducible and to be scaled for high-content screening. Compared with adherent cells grown in 2D monolayers, 3D growth conditions are believed to more closely reflect the natural environment of cancer cells. Acquiring measurements from these larger structures involve acquiring images from different depths (z-planes) within the body of the spheroid and analyzing them in 3D or collapsing the images into a single 2D stack before analysis.

• High-Throughput Confocal Imaging of Spheroids for Screening Cancer Therapeutics
• 3D Imaging of Cancer Cell Spheroids
• Functional and mechanistic neurotoxicity profiling using human iPSC-derived neural 3D cultures
• High-content 3D toxicity assay using iPSC-derived hepatocyte spheroids

Stem Cells

Stem cells are an accessible source of primary-like cells which can be used in longer-term studies to measure targeted responses in specific cell types and 3D tissues. Complex assays and 3D induced pluripotent stem cell (iPSC)-derived cell models better represent tissue biology and cell interactions which make them more relevant for many toxicity and drug screening assays.

• Multiplexed High Content Hepatotoxicity Assays Using iPSC-Derived Hepatocytes
• High-content screening of neuronal toxicity using iPSC-derived human neurons
• High-content 3D toxicity assay using iPSC-derived hepatocyte spheroids
• Stem Cell Research  

Whole Organisms

Whole organisms have greater relevance to human biology and are used in cell culture to study entire, interactive systems such as c. elegans, drosophila larvae, or zebrafish embryos. Zebrafish-based screening has gained favor as an alternative to mammalian screening due to cost, throughput, and reduced ethical concerns. Our zebrafish study uses the ImageXpress Micro System and MetaXpress software to set up and run automated imaging screens to monitor inhibition of angiogenesis, quantitate gene knockdown, and measure ototoxicity and neurotoxicity.

• High-throughput imaging assays using zebrafish, a model organism for human disease
• Novel Imaging and Analysis of Zebrafish for High Throughput Screening
• Zebrafish Actin mask w FITC vessel mask