诱导多能干细胞在遗传性心肌病细胞模型中的研究进展

Research progress of induced pluripotent stem cells in cell models of hereditary cardiomyopathy

遗传性心肌病是一类由于基因突变而引起的心肌结构和功能异常的疾病,可导致心力衰竭、心律失常甚至猝死。诱导多能干细胞的发现推动了人类多种疾病的体外研究,诱导获得的心肌细胞(CMs)为遗传性心肌病的机制研究及药物开发提供了重要的疾病细胞模型,已在基础研究中广泛应用。本文总结了遗传性心肌病的种类、临床表现以及常见的致病突变基因,以诱导多能干细胞衍生的CMs为体外模型,模拟各类遗传性心肌病的表型,并进一步挖掘由于基因突变引发的致病机制,为遗传性心肌病的遗传、分子和细胞学发病机制提供了充足的种子细胞,也为疾病的药物开发提供了研究模型。

Hereditary cardiomyopathy is a group of diseases characterized by abnormalities in myocardial structure and function due to genetic mutations,which leads to heart failure,arrhythmias and even sudden death.The discovery of induced pluripotent stem cells has promoted the in vitro study of a variety of human diseases.The cardiomyocytes obtained by induction provide important disease cell models for the study of the mechanism of hereditary cardiomyopathies and drug development and have been widely used in basic research.This article summarizs the types,clinical manifestations and common pathogenic mutated genes of hereditary cardiomyopathy,used induced pluripotent stem cell-derived cardiomyocytes as in vitro models to simulate the phenotypes of various types of hereditary cardiomyopathy,and further explores the related pathogenic mechanisms caused by gene mutations,providing sufficient seed cells for the genetic,molecular and cytological pathogenesis of hereditary cardiomyopathy.It also provides a valuable research model for drug development of diseases.