Disease modeling of desmosome-related cardiomyopathy using induced pluripotent stem cell-derived cardiomyocytes  

作　　者：Shuichiro Higo 

机构地区：[1]Department of Medical Therapeutics for Heart Failure,Osaka University Graduate School of Medicine,Suita 565-0871,Japan

出　　处：《World Journal of Stem Cells》2023年第3期71-82,共12页世界干细胞杂志（英文版）（电子版）

基　　金：Supported by JSPS KAKENHI,No.20K21602,No.21H02915,and No.22K19526;the Japan Agency for Medical Research and Development,No.21bm0804008h0005;the Cell Science Research Foundation;the Grant for Basic Research of the Japanese Circulation Society(2018);SENSHIN Medical Research Foundation.

摘　　要：Cardiomyopathy is a pathological condition characterized by cardiac pump failure due to myocardial dysfunction and the major cause of advanced heart failure requiring heart transplantation.Although optimized medical therapies have been developed for heart failure during the last few decades,some patients with cardiomyopathy exhibit advanced heart failure and are refractory to medical therapies.Desmosome,which is a dynamic cell-to-cell junctional component,maintains the structural integrity of heart tissues.Genetic mutations in desmo-somal genes cause arrhythmogenic cardiomyopathy(AC),a rare inheritable disease,and predispose patients to sudden cardiac death and heart failure.Recent advances in sequencing technologies have elucidated the genetic basis of cardiomyopathies and revealed that desmosome-related cardiomyopathy is concealed in broad cardiomyopathies.Among desmosomal genes,mutations in PKP2(which encodes PKP2)are most frequently identified in patients with AC.PKP2 deficiency causes various pathological cardiac phenotypes.Human cardiomyocytes differentiated from patient-derived induced pluripotent stem cells(iPSCs)in combination with genome editing,which allows the precise arrangement of the targeted genome,are powerful experimental tools for studying disease.This review summarizes the current issues associated with practical medicine for advanced heart failure and the recent advances in disease modeling using iPSC-derived cardiomyocytes targeting desmosome-related cardiomyopathy caused by PKP2 deficiency.

关 键 词：CARDIOMYOPATHY Advanced heart failure Induced pluripotent stem cell-derived cardiomyocytes DESMOSOME Genome editing Gene therapy 

分 类 号：R542.2[医药卫生—心血管疾病]