In vitro assessing the risk of drug-induced cardiotoxicity by embryonic stem cell-based biosensor

Abstract

Drug-induced prolongation of ventricular repolarization with arrhythmia is a major concern in clinic safety pharmacology, and has been a common reason for the withdrawal of several promising drugs from the market. Therefore, novel techniques should be developed to evaluate cardiotoxicity of new drugs in preclinical research. A cardiomyocyte based biosensor was developed using the light addressable potentiometric sensor (LAPS). Mouse embryonic stem cells cultured on the surface of LAPS were induced to differentiate into synchronized spontaneity beating cardiomyocytes. Changes of extracellular potentials and cell shapes with their mechanical beatings could induce modulation of photocurrents in the LAPS system, and finally change the output of the sensor. With the characteristics of light addressability, LAPS can record cell clusters at any desired position. The sensor can be used to record the prolongation of ventricular action potentials with the cardiotoxicity induced by drugs such as amiodarone, levofloxacin, sparfloxacin, and noradrenaline. The quick and on time characteristics of the sensor were promising to establish a high-throughput platform for pharmacological toxicity investigation.