Stem Cell Research

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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Cardiomyocytes

Stem cells differentiated into cardiomyocytes are used to screen early for potential toxicological effects of drugs, thus helping to avoid investment in development of drugs which will fail in clinical trials due to cardiac toxicity.

• Poster: Multi-parametric assessment of compound-induced pro-arrhythmic effects in human iPSC-derived cardiomyocytes
• Assaying cardiotoxicity with ImageXpress high-content screening systems
• High throughput cardiotoxicity assays using stem cell-derived cardiomyocytes
• Multiplexed automated imaging assays for compound testing using iPSC-derived cell models
• Paper: In vitro cardiotoxicity assessment of environmental chemicals using an organotypic human iPSC-derived model

Hematopoietic

Stem cells differentiated into hematopoietic progenitors (blood-forming stem cells) are important for both cell therapy and drug development. They can be used to study various blood disorders, such as leukemia or immune system disorders.

During the development of lymphoid and myeloid lineages, hematopoietic stem cells (HSCs) differentiate into committed hematopoietic progenitors. Monitoring the expansion and differentiation of HSCs into lineage-committed hematopoietic progenitors is important for research of hematopoiesis and developing therapeutic processes with HSCs.

• Poster: High throughput multiplexed assay for analysis of hematopoietic stem cells differentiation and hematopoietic toxicity
• Poster: Novel high content stem cell-based assays for screening

Hepatocytes

Stem cells differentiated into hepatocytes, or liver cells, can be used to predict liver toxicity by drug candidates. Drug-induced hepatotoxicity is an important cause for liver injury and acute liver failure. Thus, highly predictive assays for safety and efficacy testing are crucial for improving drug development. Here, we demonstrate the development of multi-parametric hepatotoxicity assays utilizing the ImageXpress Micro system. Each well or cell yields multiple compound-induced cellular responses, which are then analyzed using custom modules from MetaXpress® High-Content Image Acquisition &  Analysis Software.

• Multiplexed high-content hepatotoxicity assays using iPSC-derived hepatocytes
• Poster: Multiplexed hepatotoxicity assays using iCell® hepatocytes

Human iPSC-derived 3D neural spheroids (Stemonix microBrain 3D)

To speed up the development of more effective and safer drugs, there is an increasing need for more complex, biologically relevant, and predictive cell-based assays for drug discovery and toxicology screening. Human iPSC-derived neural 3D co-cultures (StemoniX® microBrain® 3D platform) have been developed as a high-throughput screening platform that more closely resembles the constitution of native human cortical brain tissue. 3D neural spheroids contain a neural network enriched in synapses, creating a highly functional neuronal circuitry that displays spontaneous, synchronized, readily detectable calcium oscillations.

• Phenotypic characterization of neuroactive compound effects
• Complex event analysis for neurotoxic profiling of compound effects on human iPSC-derived neural spheroid 3D cultures
• Functional evaluation of neurotoxic and neuroactive compound effects in iPSC-derived 3D neural co-cultures
• Webinar: Implementing 3D neural spheroids in drug discovery
• Poster: Multiplexed automated assays for neurotoxicity evaluation using iPSC cell-derived neural 3D cell models

Imaging cytometry enables complex cell-based assays

The ability to combine a general cell health assay with a measurement of a specific effect increases confidence in the quality of toxicity results. The SpectraMax® MiniMax™ 300 Imaging Cytometer is an intuitive platform that supplements microplate reader assays with imaging cytometry to provide more biologically relevant data to non-imaging specialists. Here, we present results of viability and toxicity assays using iPSC-derived cells performed on the imaging cytometer.

• Toxicity assays using induced pluripotent stem cell-derived cells
• Webinar: Cell-Based Assays Using a Novel Plate Reader Platform with Imaging Cytometry
• Poster: Complex cell based assays with a novel imaging cytometry system and object recognition software

Live cell time-lapse imaging

Live cell time-lapse imaging provides the ability to monitor responses in living cells over a specific period of time and offers researchers key advantages for assay development. For routine cell-based screening, time-course results can determine the correct time to read endpoint assays. Here, we demonstrate how high-content time-lapse imaging can be used to characterize cell health kinetics and to monitor cell proliferation or death of iPSC-derived neurons.

• Intelligent time-lapse imaging to enhance live cell assay development
• Webinar: Live cell imaging to investigate the regulation of cell division timing

Neuronal stem cell expansion and differentiation

There is great interest in using neuronal cells as screening tools in early drug development. However, assays that monitor the expansion and differentiation of neuronal stem cells are complex, and manual analysis can be laborious and inaccurate. Here, we demonstrate a streamlined high-content imaging and analysis workflow to automatically evaluate stem cell expansion and quantitate the extent of differentiation.

• Monitoring neuronal stem cell expansion and differentiation using high-content imaging solutions
• Poster: Novel high content stem cell-based assays for screening
• Poster: High content analysis of neural stem cell expansion and differentiation

Neurons, neurite outgrowth

Stem cells differentiated into neurons are often used in drug discovery to study central nervous system (CNS) diseases such as Alzheimer's, schizophrenia, and anxiety. These neurons can also be used in toxicological assays to help predict drug safety and efficacy.

• Identify compound-specific effects on neurite outgrowth using ImageXpress Pico system
• Assessment of neurotoxicity and neuronal development using iPSC-based neurite outgrowth assay
• High-content assay for morphological characterization of neuronal development in 3d matrix using human ipsc-derived neuronal cultures

Neurotoxicity, neuronal toxicity

High-content imaging using iPSCs of human origin can be applied to examine neurotrophic, neuroprotective, or neurotoxic effects of pharmaceutical drug candidates or environmental contaminants. This note demonstrates neuronal toxicity screening via automated endpoint and live-cell assays using iPSCs and Molecular Devices instruments and software.

• High-content screening of neuronal toxicity using iPSC-derived human neurons
• Poster – Multiplexed automated assays for neurotoxicity evaluation using induced pluripotent stem cell-derived neural 3D cell models
• Webinar: Human iPS cell-derived neurons: a new physiologically relevant model for drug discovery applications for high-content screening of neurotoxicity
• Webinar: An AI-based approach to high-content phenotypic characterization of human iPSC-derived neuronal cells

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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Phenotypic screening

eBook: Phenotypic Screening With iPSC-Derived Cardiomyocytes and Neurons

Learn how to use both imaging and calcium oscillation analysis to develop profiles of compounds in iPSC-derived cardiomyocytes such as hERG blockers, ß-adrenergic agonists, and environmental toxins. iPSC-derived neuronal cultures were evaluated with neuromodulators as well as environmental toxins.

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Toxicology

Toxicology is the study of adverse effects of natural or man-made chemicals on living organism. It is a growing concern in our world today as we are exposed to more and more chemicals, both in our environment and in the products we use.

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