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Force and Calcium Transients Analysis in Human Engineered Heart Tissues Reveals Positive Force-Frequency Relation at Physiological Frequency.
Stem Cell Reports ( IF 5.9 ) Pub Date : 2020-01-16 , DOI: 10.1016/j.stemcr.2019.12.011
Umber Saleem 1 , Ingra Mannhardt 1 , Ingke Braren 2 , Chris Denning 3 , Thomas Eschenhagen 1 , Arne Hansen 1
Affiliation  

Force measurements in ex vivo and engineered heart tissues are well established. Analysis of calcium transients (CaT) is complementary to force, and the combined analysis is meaningful to the study of cardiomyocyte biology and disease. This article describes a model of human induced pluripotent stem cell cardiomyocyte-derived engineered heart tissues (hiPSC-CM EHTs) transduced with the calcium sensor GCaMP6f followed by sequential analysis of force and CaT. Average peak analysis demonstrated the temporal sequence of the CaT preceding the contraction twitch. The pharmacological relevance of the test system was demonstrated with inotropic indicator compounds. Force-frequency relationship was analyzed in the presence of ivabradine (300 nM), which reduced spontaneous frequency and unmasked a positive correlation of force and CaT at physiological human heart beating frequency with stimulation frequency between 0.75 and 2.5 Hz (force +96%; CaT +102%). This work demonstrates the usefulness of combined force/CaT analysis and demonstrates a positive force-frequency relationship in hiPSC-CM EHTs.



中文翻译:

人体工程心脏组织中的力和钙瞬态分析揭示了生理频率上的正力-频率关系。

离体力测量和工程心脏组织已经很好地建立起来。钙瞬变(CaT)分析与力相辅相成,联合分析对心肌细胞生物学和疾病的研究具有重要意义。本文介绍了一种用钙传感器 GCaMP6f 转导的人类诱导多能干细胞心肌细胞衍生的工程心脏组织 (hiPSC-CM EHT) 模型,然后对力和 Cat 进行顺序分析。平均峰值分析显示了收缩抽搐之前的 Cat 的时间序列。测试系统的药理学相关性通过正性肌力指示剂化合物得到证实。在伊伐布雷定 (300 nM) 存在下分析力-频率关系,这降低了自发频率,并揭示了生理人心跳频率下的力和 CaT 与 0.75 和 2.5 Hz 之间的刺激频率(力 +96%;CaT +102%)之间的正相关关系。这项工作证明了联合力/CaT 分析的有用性,并证明了 hiPSC-CM EHT 中的正力-频率关系。

更新日期:2020-01-16
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