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Stem Cell Research

Automate stem cell imaging and analysis workflow of complex assays and 3D induced pluripotent stem cell (iPSC) -derived cell models

 

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.

 

Stem cell imaging

 

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.

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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.

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Automate stem cell imaging

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.

Resources of Stem Cell Research

Videos & Webinars

Implementing 3D Neural Spheroids in Drug Discovery

Multi-parameter in vitro assessment of compound effects on cardiomyocyte physiology using induced pluripotent stem cells

Human iPS Cell-derived Neurons

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

Live Cell Imaging of Co-Cultured Stem Cells

Time-Lapse Cell Migration Assay of Stem Cells

Time-Lapse Cell Migration Assay of Stem Cells

Mouse Genetically Modified Stem Cells via Transmitted Light and Fluorescence Imaging

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

Adult Stem Cells Engineered for Delivery of Therapeutic Factors

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

Live Cell Imaging to Investigate Cell Division Timing

Live Cell Imaging to Investigate the Regulation of Cell Division Timing

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

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

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