ヒト胚性または誘導性多能性幹細胞を用いた不整脈の診断と治療への再生医療技術の適用性の探求

抄録

Diagnosis and treatment of arrhythmia are not sufficiently supported by present medical care. Therefore, we studied the applicability of human embryonic (ESC) or induced pluripotent stem cells (iPSC) to the diagnosis and treatment of arrhythmia. In the study on the diagnosis of arrhythmia, we established disease-specific iPSCs from a patient with long QT syndrome type 1 (LQTS1) and confirmed electrophysiological properties of LQTS1 after the cardiac differentiation. Computer simulation of the sympathetic activation state revealed the occurrence of early afterdepolarizations, the cause of sudden cardiac death in LQTS. In the study on the treatment of arrhythmia, we selectively obtained pacemaker-, Purkinje-, ventricular myocyte-like cells from cells differentiated from human ESCs/iPSCs using HCN4 and Mlc2v genes as labeling genes. When implanted to a rat model with atrioventricular block, the pacemaker-like cells successfully functioned as a pacemaker with an ability to respond to sympathetic stimulation. In conclusion, the application of human ESCs/iPSCs to the diagnosis of arrhythmia is promising and that to the treatment of arrhythmia is feasible.