Human pluripotent stem cells: Prospects and challenges as a source of cardiomyocytes for in vitro modeling and cell-based cardiac repair

被引:102
作者
Hartman, Matthew E. [1 ,2 ,3 ,4 ]
Dai, Dao-Fu [3 ,4 ,5 ]
Laflamme, Michael A. [3 ,4 ,5 ]
机构
[1] Dept Med, Div Cardiol, New York, NY USA
[2] Dept Genome Sci, Seattle, WA USA
[3] Inst Stem Cell & Regenerat Med, New York, NY USA
[4] Ctr Cardiovasc Biol, New York, NY USA
[5] Univ Washington, Dept Pathol, Seattle, WA USA
基金
美国国家卫生研究院;
关键词
Embryonic stem cells; Induced pluripotent stem cells; Cardiac regeneration; Cardiac repair; Heart failure; Cardiovascular disease; Drug discovery; Disease modeling; CARDIOVASCULAR PROGENITOR CELLS; VENTRICULAR CARDIOMYOCYTES; ELECTRICAL-STIMULATION; FUNCTIONAL MATURATION; WNT/BETA-CATENIN; PRIMITIVE STREAK; TRANSMURAL HETEROGENEITY; SARCOPLASMIC-RETICULUM; HANDLING PROPERTIES; IMMUNE REJECTION;
D O I
10.1016/j.addr.2015.05.004
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Human pluripotent stem cells (PSCs) represent an attractive source of cardiomyocytes with potential applications including disease modeling, drug discovery and safety screening, and novel cell-based cardiac therapies. Insights from embryology have contributed to the development of efficient, reliable methods capable of generating large quantities of human PSC-cardiomyocytes with cardiac purities ranging up to 90%. However, for human PSCs to meet their full potential, the field must identify methods to generate cardiomyocyte populations that are uniform in subtype (e.g. homogeneous ventricular cardiomyocytes) and have more mature structural and functional properties. For in vivo applications, cardiomyocyte production must be highly scalable and clinical grade, and we will need to overcome challenges including graft cell death, immune rejection, arrhythmogenesis, and tumorigenic potential. Here we discuss the types of human PSCs, commonly used methods to guide their differentiation into cardiomyocytes, the phenotype of the resultant cardiomyocytes, and the remaining obstacles to their successful translation. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:3 / 17
页数:15
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