Cardiotoxicity is one of the main reasons for safety-related compound attrition and withdrawal of drugs from the market. Drug-induced cardiotoxicity is a major challenge throughout the drug discovery process. In vivo studies are limited due to low-throughput, high-cost, and species-specific differences in cardiac structure and function.
Human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) have become an attractive screening tool to identify cardiotoxic effects during early drug discovery and hold great potential for increasing drug development accuracy while reducing the time from bench-to-bedside. Importantly, hPSC-derived CMs display many of the characteristics of normal in vivo CM, including structural and electrophysiological properties. hPSC-derived CMs can provide assessment of both structural and functional cardiotoxicity potential of candidate compounds.
To guarantee a successful experimental application, it is pivotal to follow good practices when cultivating and maintaining PSCs. Concurrently, ensuring consistent and highly efficient differentiation is an important point for experimental reproducibility. Finally, fast and reliable quality control at different steps is mandatory for trustworthy results.
The StemMACS™ CardioDiff Kit XF enables robust, standardized, and scalable cardiac differentiation, without the need for adding supplementary factors. The kit ensures high differentiation efficiency and experiment-to-experiment consistency. hPSC-derived CMs obtained with the StemMACS CardioDiff Kit XF express characteristic markers (cTnT, alpha actinin, MHC), show typical morphology and normal action potentials. Co-staining of depletion and enrichment markers with the PSC-derived Cardiomyocyte Isolation Kit, human enables further purification of CMs. The results show that PSC-derived CMs are highly functional and display the appropriate structural characteristics crucial for reliable cardiotoxicity.
Kristin Becker, Jens-Peter Derks, Jona Drushku, Andreas Bosio, Sebastian Knöbel, and Dominik Eckardt; Miltenyi Biotec, Bergisch Gladbach, Germany
Scientists have made great strides in improving cellular models that permit high-throughput screens to identify and characterize therapeutic candidates. For example, researchers now derive cardiomyocytes from human pluripotent stem cells (PSCs) to study a compound’s effect on cardiac function. To guarantee the experimental success and reproducibility of PSC-based high-throughput screens, researchers must apply good PSC culturing practices, ensure consistent and efficient differentiation, and incorporate quality controls at various steps. In this webinar, brought to you by Miltenyi Biotec, experts will present a complete workflow to perform high-throughput screens with PSC-derived cardiomyocytes.
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