The xCELLigence RTCA ePacer is an innovative solution for maturing human iPSC Cardiomyocytes into a more predictive model for drug discovery, safety pharmacology, and cardiac disease research
Human-induced pluripotent stem cell cardiomyocytes are actively utilized in the academic and biopharma industries for safety/tox assessment, drug discovery, and investigation as cardiac disease models. The biggest gap in the field for full adoption of these cells are their inherent immature characteristics.
A number of natural engineering approaches attempting to enhance the structural and functional maturity of hiPSC-CM's have been described in literature, including co-culture, mechanical conditioning, use of ECM substrates with different degrees of stiffness, and electrical pacing.
Efficient propagation of electrical signals is a crucial aspect of the cardiomyocyte developmental program and functionality. The xCELLigence RTCA ePacer is designed to use a natural development program of in vivo stimuli for cardiomyocyte “maturation” in a consistent, tunable, scalable, and high-throughput manner that is compatible with different types of relevant readouts.
The xCELLigence RTCA ePacer provides an easy and effective way to produce functionally mature hiPSC cardiomyocytes. Under precise and consistent electrical pacing conditions, the ePacer improves the maturation status of the hiPSC cardiomyocytes in just 2-3 weeks, without any detectable toxicity or stress to the cells.
Figure 2: After being subjected to directed progressive electrical pacing using the xCELLigence RTCA ePacer, the hiPSC cardiomyocytes were able to demonstrate A. positive force-frequency relationship and appropriate contractile responses to inotropes; B. significantly improved organized sarcomere structure; and C. proper gene expression.
The xCELLigence RTCA ePacer is adaptable and can easily integrate into your existing assay workflow. The view area on the E-Plate Cardio View 96 allows for integration of paced cells with other optical assays.
After being subjected to long-term electrical pacing on the xCELLigence RTCA ePacer, contractile and electrical responses of the hiPSC cardiomyocytes can be assessed using the xCELLigence RTCA CardioECR system; alternatively, the contractile responses can be evaluated using the xCELLigence RTCA Cardio system.
After long-term electrical pacing using the xCELLigence RTCA ePacer, iCell® Cardiomyocytes2 were preincubated with Ca2+ dye and buffer for 1 hour. The Ca2+ signals were then measured using the Hamamatsu FDSS/μCELL before and after DMSO and ISO addition.
After being subjected to a long-term electrical pacing using the xCELLigence RTCA ePacer, iCell Cardiomyocytes2 were immunostained for cardiac troponin C (green) and nuclei (blue) right on the E-Plate® Cardio VIEW 96. The image (20X) was obtained using ImageXpress® Micro confocal.