Human Engineered Heart Tissue: Analysis of Contractile Force

被引：273

作者：

Mannhardt, Ingra ^{[1
]}

Breckwoldt, Kaja ^{[1
]}

Letuffe-Breniere, David ^{[1
]}

Schaaf, Sebastian ^{[1
]}

Schulz, Herbert ^{[2
,3
]}

Neuber, Christiane ^{[1
]}

Benzin, Anika ^{[1
]}

Werner, Tessa ^{[1
]}

Eder, Alexandra ^{[1
]}

Schulze, Thomas ^{[1
]}

Klampe, Birgit ^{[1
]}

Christ, Torsten ^{[1
]}

Hirt, Marc N. ^{[1
]}

Huebner, Norbert ^{[2
]}

Moretti, Alessandra ^{[4
]}

Eschenhagen, Thomas ^{[1
]}

Hansen, Arne ^{[1
]}

机构：

[1] DZHK German Ctr Cardiovasc Res, Univ Med Ctr Hamburg Eppendorf, Cardiovasc Res Ctr, Dept Expt Pharmacol & Toxicol, Partner Site Hamburg Kiel Lubeck, D-20246 Hamburg, Germany

[2] DZHK German Ctr Cardiovasc Res, Max Delbrueck Ctr Mol Med MDC, Partner Site Berlin, D-13092 Berlin, Germany

[3] Univ Cologne, Cologne Ctr Genom CCG, D-50931 Cologne, Germany

[4] Tech Univ Munich, DZHK German Ctr Cardiovasc Res, Klinikum Rechts Isar, Med Dept Cardiol 1,Partner Site Munich Heart Alli, D-81675 Munich, Germany

来源：

STEM CELL REPORTS | 2016年 / 7卷 / 01期

基金：

英国国家替代、减少和改良动物研究中心; 欧洲研究理事会;

关键词：

CELL-DERIVED CARDIOMYOCYTES; PLURIPOTENT STEM-CELLS; TORSADE-DE-POINTES; CARDIAC-HYPERTROPHY; ACTION-POTENTIALS; RISK-ASSESSMENT; IN-VITRO; MATURATION; CHANNELS; MYOCARDIUM;

D O I：

10.1016/j.stemcr.2016.04.011

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Analyzing contractile force, the most important and best understood function of cardiomyocytes in vivo is not established in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). This study describes the generation of 3D, strip-format, force-generating engineered heart tissues (EHT) from hiPSC-CM and their physiological and pharmacological properties. CM were differentiated from hiPSC by a growth factor-based three-stage protocol. EHTs were generated and analyzed histologically and functionally. HiPSC-CM in EHTs showed well-developed sarcomeric organization and alignment, and frequent mitochondria. Systematic contractility analysis (26 concentration-response curves) reveals that EHTs replicated canonical response to physiological and pharmacological regulators of inotropy, membrane-and calcium-clock mediators of pacemaking, modulators of ion-channel currents, and proarrhythmic compounds with unprecedented precision. The analysis demonstrates a high degree of similarity between hiPSC-CM in EHT format and native human heart tissue, indicating that human EHTs are useful for preclinical drug testing and disease modeling.

引用

页码：29 / 42

页数：14

共 60 条

[1] A TTX-sensitive inward sodium current contributes to spontaneous activity in newborn rabbit sino-atrial node cells [J].