作者: Luca Sala , Dorien Ward-van Oostwaard , Leon G. J. Tertoolen , Christine L Mummery , Milena Bellin
DOI: 10.3791/55587
关键词: Induced pluripotent stem cell 、 Pharmacology 、 Embryonic stem cell 、 Electrophysiology 、 Safety pharmacology 、 Neuroscience 、 Cardiac arrhythmia 、 Stem cell 、 Long QT syndrome 、 Myocyte 、 Medicine
摘要: Cardiomyocytes can now be derived with high efficiency from both human embryonic and induced-Pluripotent Stem Cells (hPSC). hPSC-derived cardiomyocytes (hPSC-CMs) are increasingly recognized as having great value for modeling cardiovascular diseases in humans, especially arrhythmia syndromes. They have also demonstrated relevance vitro systems predicting drug responses, which makes them potentially useful drug-screening discovery, safety pharmacology perhaps eventually personalized medicine. This would facilitated by deriving hPSC-CMs patients or susceptible individuals hiPSCs. For all applications, however, precise measurement analysis of hPSC-CM electrical properties essential identifying changes due to cardiac ion channel mutations and/or drugs that target channels cause sudden death. Compared manual patch-clamp, multi-electrode array (MEA) devices offer the advantage allowing medium- high-throughput recordings. protocol describes how dissociate 2D cell cultures small aggregates single cells plate on MEAs record their spontaneous activity field potential. Methods analyzing recorded data extract specific parameters, such QT RR intervals, described here. Changes these parameters expected carrying responsible arrhythmias following addition drugs, detection those carry a cardiotoxic risk.