Stem Cell Research
Stem cells provide researchers with new opportunities to study targets and pathways that are more relevant to disease processes. They offer 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.
Induced pluripotent stem cell-derived (iPSC-derived) cells enable researchers to study primary cells without the limitations traditionally encountered in obtaining such cells.
Benefits of stem cell research
The biopharma industry is continuing to adapt more cell-based assays for primary and secondary screening because of higher biological relevance and increased value of information. As part of this evolution, there is a desire to move from immortalized, stable cell lines to primary cells and stem cells. Stem cells offer the advantages of providing better clinical relevance of information compared to cell lines, being available in larger quantities, and having higher assay reproducibility than primary cells. Therefore, there is a great interest in automated stem cell assays to use as screening tools in early drug development, and to evaluate potential toxic effects of new compounds.
The workflows for assays involving stem cells are similar to other cell-based assays, but there are critical differences. Differentiation is often involved in stem cell assays because of the need to start with undifferentiated cells, or because the assay is studying the differentiation process. Monitoring the type and number of cells is often important when more than one lineage is present, or when both mature and undifferentiated cells are present. Accordingly, the data analysis and visualization requirements become more complex as multiple readouts from multiple cell types are required.
Stem cell imaging – High-content screening techniques and tools
Complex assays and 3D iPSC-derived cell models better represent tissue biology and cell interactions, making them more relevant for many toxicity and drug screening assays. As a result, the development of higher throughput quantitative assays using 3D cultures is an active area of investigation. Complicated 3D image acquisition and analysis workflows make it difficult to scale these assays for screening.
The ImageXpress® Micro High-Content Imaging Systems and MetaXpress® 3D Analysis Module allow us to implement a simpler workflow to quantify and visualize 3D structures.
Hepatotoxicity assay using 3D spheroid liver micro tissues derived from iCell Hepatocytes.
(A) iCell Hepatocytes were grown in 2D format for seven days prior to using them to prepare 3D cultures. Following spheroid formation, the liver micro tissues were treated with compounds for 72 hours, then stained for two hours and imaged. Z-planes were acquired using the ImageXpress Micro Confocal system.
(B) The acquired z-plane images were used to generate sets of 2D and 3D image segmentation, which were analyzed to quantify key phenotypic features of the 3D cultures.
Automate stem cell imaging utilizing iPSC-derived cardiomyocytes, neurons, and hepatocytes
There is a great need to automate complex cell-based assays with multi-parametric readouts while maintaining high data quality and precision. A compact, automated imaging microplate reader was used to develop several multi-parametric assays utilizing iPSC-derived cardiomyocytes, neurons, and hepatocytes. Multiple readouts include cell viability, apoptosis, mitochondria membrane potential and autophagy for defining mechanisms of toxicity in live or fixed cells. Also, we provide examples of label–free cell analysis for evaluation of cytotoxicity and cell proliferation. We demonstrate the utility of a new automated imaging system for biological research and present several assay models that will be useful for both academic and bio-pharma environments.
Cell-based assays were performed using the ImageXpress® Pico Automated Cell Imaging System in combination with the CellReporterXpress Automated Imaging and Analysis Software. The imager provides 4 fluorescence channels plus transmitted light time-lapse capacity to enable automatic monitoring of cell proliferation, differentiation, compound toxicity, and a variety of other cell-based assays.

Stem cell applications and the tools to transform your data into unique biological insights
The stem cell workflow demands a variety of complex assay types that monitor all phases from initial growth and expansion to differentiation, to quality control, and finally predictive assays for therapeutic research and drug discovery. Our suite of hardware and software solutions enable automated analysis of stem cells for many of the steps in the workflow. We are continuing to develop new techniques to help further condense and automate the workflow for stem cell assays.
-
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.
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
- Multiplexed automated imaging assay for cardiotoxic compounds using the ImageXpress Pico system
- 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.
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.
-
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.
-
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.
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.
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.
Resources of Stem Cell Research
Application Note
Multi-parametric assessment of compound-induced pro-arrhythmic effects in human iPSC-derived cardiomyocytes
Multi-parametric assessment of compound-induced pro-arrhythmic effects in human iPSC-derived cardiomyocytes
Development of biologically relevant, predictive cell-based assays for compound screening and toxicity assessment is a major challenge in drug discovery.
Scientific Poster
AI-based analysis of complex biological phenotypes
AI-based analysis of complex biological phenotypes
Cell-based phenotypic assays have become an increasingly attractive alternative to traditional in vitro and in vivo testing in pharmaceutical drug development and toxicological safety ass…
Application Note
Phenotypic characterization of neuroactive compound effects
Phenotypic characterization of neuroactive compound effects
The FLIPR Penta system is powered by a high-speed EMCCD camera and the new ScreenWorks Peak Pro 2 software. The system allows measurement and analysis of complex patterns of calcium…
Scientific Poster
Multiplexed automated assays for neurotoxicity evaluation using induced pluripotent stem cell-derived neural 3D cell models
Multiplexed automated assays for neurotoxicity evaluation using induced pluripotent stem cell-derived neural 3D cell models
Cell-based phenotypic assays have become an increasingly attractive alternative to traditional in vitro and in vivo testing in pharmaceutical drug development and toxicological safety ass…
Scientific Poster
Complex event analysis for neurotoxic profiling of compound effects on human iPSC-derived neural spheroid 3D cultures
Complex event analysis for neurotoxic profiling of compound effects on human iPSC-derived neural spheroid 3D cultures
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…
Application Note
Functional evaluation of neurotoxic and neuroactive compound effects in iPSC-derived 3D neural co-cultures
Functional evaluation of neurotoxic and neuroactive compound effects in iPSC-derived 3D neural co-cultures
There is increasing interest in using more complex, biologically-relevant, and predictive cell-based platforms for assay development and compound screening.
Application Note
Multiplexed automated imaging assay for cardiotoxic compounds using the ImageXpress Pico system
Multiplexed automated imaging assay for cardiotoxic compounds using the ImageXpress Pico system
Develop functional and morphological readouts for testing effects of different compounds in multi-parametric assays using iPSC-derived cardiomyocytes
Application Note
Identify compound-specific effects on neurite outgrowth using ImageXpress Pico system
Identify compound-specific effects on neurite outgrowth using ImageXpress Pico system
Evaluate compound-specific effects on neurite outgrowth using automated imaging
Application Note
Measure Calcium Oscillation in iCell Cardiomyocytes2 on the FLIPR Tetra System
Measure Calcium Oscillation in iCell Cardiomyocytes2 on the FLIPR Tetra System
Shorten growth timelines when screening compound effects on calcium transients in beating cardiomyocytes by using the iCell® Cardiomyocytes2 Kit (Cellular Dynamics International). iCell…
Application Note
High-Content Assay for Morphological Characterization of Neuronal Development in a 3D Matrix using Human iPSC-Derived Neuronal Cultures
High-Content Assay for Morphological Characterization of Neuronal Development in a 3D Matrix using Human iPSC-Derived Neuronal Cultures
Development of more complex, biologically relevant, and predictive cellbased assays for compound screening is a primary challenge in drug discovery. The development and integration of three…
Application Note
Assessment of neurotoxicity and neuronal development using induced pluripotent stem cell-based neurite outgrowth assay
Assessment of neurotoxicity and neuronal development using induced pluripotent stem cell-based neurite outgrowth assay
Growing concerns about the increased prevalence of untested chemicals in the environment has created a pressing need to develop reliable and efficient screening tools to identify chemicals…
Scientific Poster
High Throughput Multiplexed Assay for Analysis of Hematopoietic Stem Cells Differentiation and Hematopoietic Toxicity
High Throughput Multiplexed Assay for Analysis of Hematopoietic Stem Cells Differentiation and Hematopoietic Toxicity
PDF reveals the ability of IsoCyte laser scanning system used with FCS Express software to qualify expression of lineage specific and stem cell markers of hematopoietic cells.
Scientific Poster
Multiplexed Hepatotoxicity Assays using iCell® Hepatocytes
Multiplexed Hepatotoxicity Assays using iCell® Hepatocytes
Predictive in vitro assays suitable for safety testing are extremely important for reducing the incidence of late-stage drug attrition. We have paired human iPSCderived hepatocytes with t…
Scientific Poster
Novel High Content Stem Cell-based Assays for Screening
Novel High Content Stem Cell-based Assays for Screening
The biopharma industry is continuing to adapt more cell-based assays for primary and secondary screening because of higher biological relevance and increased value of information.
Scientific Poster
High Content Analysis of Neural Stem Cell Expansion and Differentiation
High Content Analysis of Neural Stem Cell Expansion and Differentiation
This application note describes the accurate image on the wells of this novel culture system with ImageXpress Micro High-Content Imaging Systems to visualize & quantify cytotoxic expo…
Scientific Poster
Novel Functional Phenotypes In Induced Pluripotent Stem Cell-derived Neurons From Patients With LRRK2 G2019S Mutation
Novel Functional Phenotypes In Induced Pluripotent Stem Cell-derived Neurons From Patients With LRRK2 G2019S Mutation
Virtually all experimental models aimed at mimicking Parkinson’s disease (PD) are limited in their ability to faithfully replicate disease phenotypes. A great hope relies on new patient-s…
eBook
Stem Cell Imaging
Stem Cell Imaging
Scientists’ expanding knowledge and understanding of stem cells is transforming the way we research human biology and medicine. Stem cells’ ability to differentiate into a variety of huma…
Application Note
Toxicity assays using induced pluripotent stem cell-derived cells
Toxicity assays using induced pluripotent stem cell-derived cells
Drug-induced organ toxicity is an important cause of pharmaceutical candidates failing to make it to market. Thus highly predictive assays for safety and efficacy testing are crucial for…
Application Note
High-content assay for morphological characterization of 3D neuronal networks in a microfluidic platform
High-content assay for morphological characterization of 3D neuronal networks in a microfluidic platform
Establishment of physiologically-relevant in vitro models is crucial to further understanding of the mechanisms of neurological diseases as well as targeted drug development. While iPSC-…
Application Note
Phenotypic characterization of toxic compound effects on cardiomyocytes derived from induced pluripotent stem cells
Phenotypic characterization of toxic compound effects on cardiomyocytes derived from induced pluripotent stem cells
Cardiotoxicity remains a primary cause for drug attrition during clinical trials and post-marketing. While it is believed that a significant percentage of cardiovascular diseases are due to…
Application Note
Stem Cell-Derived Human Neurons in CNS Drug Discovery
Stem Cell-Derived Human Neurons in CNS Drug Discovery
Central nervous system (CNS) disorders affect many people worldwide. To increase the quality and number of drugs available for treatments of CNS disorders such as Alzheimer’s disease,…
Application Note
Selecting clones of mouse embryonic stem cells
Selecting clones of mouse embryonic stem cells
The targeted propagation of undifferentiated cells is of particular interest in mouse embryonic stem cell (mESC) culture and cell line development. The technology in ClonePix Systems lends…
Application Note
High throughput cardiotoxicity assays using stem cell-derived cardiomyocytes
High throughput cardiotoxicity assays using stem cell-derived cardiomyocytes
Eliminate cardiotoxic compounds and identify potential cardiac drug candidates earlier in the drug discovery process with the FLIPR Tetra System, together with ScreenWorks Peak Pro Software…
Application Note
Compound effects upon calcium transients in beating Axiogenesis Cor.4U human iPS cell-derived cardiomyocytes
Compound effects upon calcium transients in beating Axiogenesis Cor.4U human iPS cell-derived cardiomyocytes
The assessment of cardiotoxicity is important in the early stages of drug discovery to enable elimination of potentially toxic compounds from further development. This is critical to reduce…
Application Note
Assaying cardiotoxicity with ImageXpress high-content screening systems
Assaying cardiotoxicity with ImageXpress high-content screening systems
The discovery and development of novel drugs is a difficult and expensive process due to lack of tools and techniques to accurately reproduce the human physiological response in the…
Application Note
High-content screening of neuronal toxicity using iPSC-derived human neurons
High-content screening of neuronal toxicity using iPSC-derived human neurons
The nervous system is sensitive to the toxic effects of many chemical compounds, environmental agents and certain naturally occurring substances. Neurotoxicity can cause temporary or…
Application Note
Intelligent time-lapse imaging to enhance live cell assay development
Intelligent time-lapse imaging to enhance live cell assay development
The ability to monitor responses in living cells over a specific period of time offers cell biologists several key advantages for assay development. For routine cellbased screening, time-…
Application Note
Multiplexed high-content hepatotoxicity assays using iPSC-derived hepatocytes
Multiplexed high-content hepatotoxicity assays using iPSC-derived hepatocytes
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…
Scientific Poster
In Vitro Cardiotoxicity and Neurotoxicity Assessment of Environmental Chemicals Using Organotypic Human Induced Pluripotent Stem Cell-Derived Models
In Vitro Cardiotoxicity and Neurotoxicity Assessment of Environmental Chemicals Using Organotypic Human Induced Pluripotent Stem Cell-Derived Models
An increased prevalence of neurological and cardiovascular disorders, possibly attributed to environmental toxicant exposures, has generated an interest in developing reliable and efficie…
Scientific Poster
High-Content Assay for Morphological Characterization of Neuronal Development in 3D Matrix Using Human iPSC-Derived Neuronal Cultures
High-Content Assay for Morphological Characterization of Neuronal Development in 3D Matrix Using Human iPSC-Derived Neuronal Cultures
Development of more complex, biologically relevant, and predictive cell-based assays for compound screening is one of the main challenges in drug discovery. There is an increasing interes…
Scientific Poster
Complex Cell Based Assays with a Novel Imaging Cytometry System and Object Recognition Software
Complex Cell Based Assays with a Novel Imaging Cytometry System and Object Recognition Software
Learn how to run complex cell-based assays while maintaining high-quality multi-parametric data output using a novel imaging cytometry system and object recognition software.
Videos & Webinars

Human iPS Cell-derived Neurons: A New Physiologically Relevant Model for Drug Discovery Applications for High-Content Screening of Neurotoxicity

Live Cell Imaging of Co-Cultured Stem Cells

Time-Lapse Cell Migration Assay of Stem Cells

Mouse Genetically-Modified Stem Cells via Transmitted Light and Fluorescence Imaging

High Throughput Characterization of Adult Stem Cells Engineered for Delivery of Therapeutic Factors for Neuroprotective Strategies

Live Cell Imaging to Investigate the Regulation of Cell Division Timing

Cell-Based Assays Using a Novel Plate Reader Platform with Imaging Cytometry