Improved Computational Identification of Drug Response Using Optical Measurements of Human Stem Cell Derived Cardiomyocytes in Microphysiological Systems.

摘要: Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) hold great potential for drug screening applications. However, their usefulness is limited by the relative immaturity of cells' electrophysiological properties as compared to native cardiomyocytes in adult heart. In this work, we extend and improve on methodology address limitation, building previously introduced computational procedures which predict effects based changes optical measurements action potentials Ca2+ transients made cell cardiac microtissues. This quantifies ion channel through inversion data into a mathematical model, maps response an phenotype assumption functional invariance fundamental intracellular membrane channels during maturation. Here, utilize updated model represent both hiPSC-CMs cardiomyocytes, apply IC50-based dose-dependent effects, introduce continuation-based optimization algorithm analysis dose escalation using five drugs with known effects. The improved can identify more efficiently, quantitate important metrics such IC50 line published values. Consequently, step towards employing elucidate new cell-derived experimental tissues.