3D Cell Models

3D Cancer Cell Research

Cancer involves changes which enable cells to grow and divide without respect to normal limits, to invade and destroy adjacent tissues, and ultimately to metastasize to distant sites in the body. Cancer spheroids mimic tumor behavior far more effectively than standard 2D cell cultures. Such 3D spheroid models are being successfully used in screening environments for identifying potential cancer therapeutics.

Cancer researchers need tools that enable them to more easily study the complex and often poorly understood interactions between cancerous cells and their environment, and to identify points of therapeutic intervention.

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3D neural spheroids

To accelerate the development of effective and safe drugs, there is an increasing need for more complex, biologically relevant, and predictive cell-based assays for drug discovery and toxicology screening.

We show that functional and morphological assays using 3D neural spheroids formed with human iPSC-derived cells can be used for evaluation of drug candidates and neurotoxicity assessment.

• Webinar: Implementing 3D neural spheroids in drug discovery
• Phenotypic characterization of neuroactive compound effects
• Functional evaluation of neurotoxic and neuroactive compound effects in iPSC-derived 3D neural co-cultures

Cardiotoxicity

Live-cell imaging and 3D models provide greater predictivity for compound ecacy and toxicity. We present methods for the formation of 3D spheroids derived from human iPSC-derived cells.

• Analyze cardiomyocyte spheroid contractions
• Assessment of drug effects on cardiomyocyte physiology using human iPSC-derived cardiac spheroids
• In vitro assessment of drug effects on human iPSC-derived cardiac spheroid cultures

Cells in Extracellular 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

Disease modeling using novel flowchip system

Disease Modeling with 3D Cell-Based Assays Using a Novel Flowchip System and High-Content Imaging

There is an increasing interest in using three-dimensional (3D) cell structures for modeling tumors, organs, and tissue to accelerate translational research. We describe here a novel automated organoid assay system (the Pu·MA System) combined with microfluidic-based flowchips that can facilitate 3D cell-based assays.

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Organoid Innovation Center

The new Organoid Innovation Center at Molecular Devices combines cutting-edge technologies with novel 3D biology methods to address key challenges of scaling complex 3D biology.

The collaborative space brings customers and researchers into the lab to test automated workflows for organoid culturing and screening, with guidance from in-house scientists.

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Organoid technology / Organ-on-a-Chip

Organoid technology, like organ-on-a-chip emulates organ physiology though co-culture of cells in a supportive 3D matrix and use of microfluidic channels to perfuse nutrients or compounds over the resulting cellular structures. It is rapidly gaining popularity as a biologically relevant screening model for new drugs and toxicity.

• 3D image analysis and characterization of angiogenesis in organ-on-a-chip model
• Video: Physiologically-Relevant Tissue Models Using a High-Throughput Organ-on-a-Chip Platform
• High-content assay for morphological characterization of 3D neuronal networks in a microfluidic 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.

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Organoids

Organoids are three-dimensional (3D) multi-cellular microtissues that are designed to closely mimic the complex structure and functionality of human organs. Organoids typically consist of a co-culture of cells which demonstrate a high order of self-assembly to allow for an even better representation of complex in vivo cell responses and interactions, as compared to traditional 2D cell cultures.

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Spheroids

Spheroids are multi-cellular 3D structures that mimic in vivo cell responses and interactions. They can 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.

• 3D Imaging of Cancer Cell Spheroids
• High-Throughput Confocal Imaging of Spheroids for Screening Cancer Therapeutics
• Functional and mechanistic neurotoxicity profiling using human iPSC-derived neural 3D cultures
• High-content 3D toxicity assay using iPSC-derived hepatocyte spheroids
• Acquire and analyze images of FUCCI spheroids
• Assay apoptosis in magnetically bioprinted HepG2 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

Model systems such as Drosophila, C. elegans, and zebrafish offer relevance to human biology, with the added advantage of genetic and whole-organism phenotypic screening. Zebrafish screening has gained favor as an alternative to mammalian screening due to reduced cost and space requirements, short generation times, and ease of genetic manipulation. Our zebrafish studies use 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