#Talking3RScience Webinar Serie

Udo Kraushaar & Michele Dipalo

NMI Natural and Medical Sciences Institute & Istituto Italiano di Tecnologia

„Securing Cardiac Safety: Advancements in In Vitro Approaches„

The cardiac action potential, critical for heart function, relies on precise ion channel timing. Deviations, such as the blockage of voltage-gated potassium channels, can lead to life-threatening arrhythmias, highlighting the limitations of traditional cellular assays that use cells expressing single ion channel types and often result in the premature exclusion of potentially therapeutic compounds. The advent of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) has revolutionized cardiac safety evaluation, offering more physiologically relevant drug screening platforms and enabling the creation of patient-derived disease models.

Technologies including microelectrode array (MEA) technology and live-cell calcium imaging have emerged as powerful in vitro alternatives for cardiac safety assessments. MEA systems non-invasively record cardiac field potentials, providing insights into beat rate, conduction velocity, and indications of arrhythmogenic potential with increased-throughput efficiency. Moreover, the recent use of photonics is further expanding MEA capabilities toward more reliable ion channel characterizations and long-term safety studies. This also aligns with broader efforts, such as the Comprehensive in vitro Proarrhythmia Assessment (CiPA) initiative, to improve regulatory standards for cardiac safety. Live-cell calcium imaging, on the other hand, sheds light on intracellular calcium dynamics crucial for cardiac muscle contraction. Together, these technologies offer a comprehensive view of drug effects on heart function, reducing reliance on animal testing and enhancing the drug development process by identifying cardiac liabilities earlier.

This webinar will explore the integration of MEA and other techniques in drug development, emphasizing their role in improving the prediction of drug-induced cardiac risks. By focusing on these advanced in vitro techniques, we aim to illustrate their potential in fostering the development of safer therapeutic agents.