From 2D to 3D spheroid models for drug-induced cardiotoxicity assessment:  integrating functional, electrophysiological, and molecular safety pharmacology endpoints

From 2D to 3D spheroid models for drug-induced cardiotoxicity assessment: integrating functional, electrophysiological, and molecular safety pharmacology endpoints

Summary

Researchers at Yashraj Biotechnology Ltd. validated a hiPSC-derived cardiomyocyte platform (YBLiCardio) on a multi-electrode array against the full 28-compound CiPA reference set, reproducing the expected rank order of proarrhythmic risk with complete separation of high-risk from low-risk compounds. They also characterized matched 3D cardiac spheroids, which showed more mature calcium handling and higher expression of maturation and ventricular markers (MYH7, MYL2, HCN4, CACNA1C) while preserving cardiac identity. These preliminary findings support 3D spheroids as a candidate platform for proarrhythmia assessment, with direct electrophysiology in 3D as the next step.