A Change of Heart: Human Cardiac Tissue Engineering as a Platform for Drug Development

被引:16
作者
Bremner, Samantha B. [1 ,5 ]
Gaffney, Karen S. [1 ]
Sniadecki, Nathan J. [1 ,2 ,3 ,4 ,5 ]
Mack, David L. [1 ,5 ,6 ]
机构
[1] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA
[2] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA
[3] Univ Washington, Dept Lab Med & Pathol, Seattle, WA 98195 USA
[4] Univ Washington, Ctr Cardiovasc Biol, Seattle, WA 98195 USA
[5] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA
[6] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA
关键词
Cardiac tissue engineering; Pluripotent stem cells; Drug screening; Cardiotoxicity; PLURIPOTENT STEM-CELLS; LARGE ANIMAL-MODELS; PROMOTES MATURATION; CARDIOMYOCYTES; CONTRACTILITY; STRETCH; DIFFERENTIATION; REVEALS; DISEASE; MUSCLE;
D O I
10.1007/s11886-022-01668-7
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose of Review Human cardiac tissue engineering holds great promise for early detection of drug-related cardiac toxicity and arrhythmogenicity during drug discovery and development. We describe shortcomings of the current drug development pathway, recent advances in the development of cardiac tissue constructs as drug testing platforms, and the challenges remaining in their widespread adoption. Recent Findings Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been used to develop a variety of constructs including cardiac spheroids, microtissues, strips, rings, and chambers. Several ambitious studies have used these constructs to test a significant number of drugs, and while most have shown proper negative inotropic and arrhythmogenic responses, few have been able to demonstrate positive inotropy, indicative of relative hPSC-CM immaturity. Several engineered human cardiac tissue platforms have demonstrated native cardiac physiology and proper drug responses. Future studies addressing hPSC-CM immaturity and inclusion of patient-specific cell lines will further advance the utility of such models for in vitro drug development.
引用
收藏
页码:473 / 486
页数:14
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