诱导多能干细胞在遗传性心脏疾病模型中的应用与机制  

Application and mechanism of induced pluripotent stem cells in inherited heart disease models

作　　者：马阳光 张雅永[1] 孟明耀[1] 金志豪 李映明 黄耀萱 韩燊[1] 李亚雄[1] Ma Yangguang;Zhang Yayong;Meng Mingyao;Jin Zhihao;Li Yingming;Huang Yaoxuan;Han Shen;Li Yaxiong(Yan’an Affiliated Hospital of Kunming Medical University,Kunming 650051,Yunnan Province,China)

机构地区：[1]昆明医科大学附属昆明市延安医院,云南省昆明市650051

出　　处：《中国组织工程研究》2024年第25期4072-4078,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(82260063),项目负责人:韩燊;云南省心血管疾病重点实验室(2018DG008),项目负责人:李亚雄;云南省应用基础研究专项(202201AT070282),项目负责人:韩燊;云南省应用基础研究计划-昆医联合专项(202101AY070001-211),项目负责人:韩燊;云南省心血管系统疾病临床医学研究中心项目(202102AA310003-11),项目负责人:韩燊。

摘　　要：背景:遗传性心脏病具有较高的患病率及死亡率,至今其发病机制仍未阐明。尽管部分遗传性心脏病已经建立了相应的动物模型,为研究遗传性心脏病的发病机制提供了一定的基础,但是由于物种间的差异等原因显著降低了这些研究结果的价值,因此,需要全新的模型来探索其发生发展过程。目的:综述了目前诱导多能干细胞在构建多种遗传性心脏病模型中的作用和潜在的应用前景。方法:第一作者于2023年1-3月期间应用计算机在Pub Med数据库中检索近13年的相关文献,以“induced pluripotent stem cell,inherited heart disease,congenital heart disease”等为检索词,最终纳入76篇文献进行分析。结果与结论:自2007年诱导多能干细胞从人体体细胞中诱导建立以来,已有许多针对疾病特异性诱导多能干细胞的研究报道。由于疾病特异性诱导多能干细胞能够再现疾病表型,因此有望成为体外疾病建模的一种新研究工具,用于分析发病机制和研制辅助药物。在心血管遗传性疾病的研究方面,从患者特异性诱导多能干细胞分化得到的心肌细胞中含有参与心脏发育异常相关的基因突变,因此,其可作为一种全新的工具研究遗传性心脏病的潜在机制。到目前为止,诱导多能干细胞来源心肌细胞已被广泛用于多种遗传性心脏疾病的分子机制研究,如心脏电生理性疾病、心肌病以及一些综合征性遗传性心脏疾病。BACKGROUND:Inherited heart disease has a high prevalence and mortality rate,but its pathogenesis has not yet been clarified.Although relevant animal models have been established to provide a foundation for the pathogenesis research of inherited heart disease,the value of these research results has been significantly reduced due to differences among species.Therefore,a new model is needed to explore its occurrence and development.OBJECTIVE:To review the current role of induced pluripotent stem cells in disease modeling and potential application prospects in various inherited heart diseases.METHODS:The first author searched the relevant articles published nearly 13 years in PubMed from January to March 2023.The search terms were“induced pluripotent stem cell,inherited heart disease,congenital heart disease”.Finally,76 articles were included for analysis.RESULTS AND CONCLUSION:Since 2007,when induced pluripotent stem cells were induced from human somatic cells,many studies have been reported on disease-specific induced pluripotent stem cells.Due to the ability of disease-specific induced pluripotent stem cells to reproduce disease phenotypes,they are expected to become a new research tool for in vitro disease modeling,used to analyze pathogenesis and develop auxiliary drugs.In the research of cardiovascular genetic diseases,cardiomyocytes derived from patient-specific induced pluripotent stem cells contain gene mutations that are involved in cardiac dysplasia.Therefore,it can be used as a new tool to study the potential mechanisms of inherited heart disease.Up to now,induced pluripotent stem cells-derived cardiomyocytes have been widely used to study the molecular mechanisms of various genetic heart diseases,such as cardiac electrophysiological diseases,cardiomyopathy,and some syndromic inherited heart diseases.

关 键 词：遗传性心脏病 诱导多能干细胞 心肌细胞 疾病模型 

分 类 号：R459.9[医药卫生—治疗学] R364[医药卫生—临床医学] R654.2