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Comparison of 10 Control hPSC Lines for Drug Screening in an Engineered Heart Tissue Format
Stem Cell Reports ( IF 5.9 ) Pub Date : 2020-10-13 , DOI: 10.1016/j.stemcr.2020.09.002
Ingra Mannhardt 1 , Umber Saleem 1 , Diogo Mosqueira 2 , Malte F Loos 1 , Bärbel M Ulmer 1 , Marc D Lemoine 3 , Camilla Larsson 4 , Caroline Améen 4 , Tessa de Korte 5 , Maria L H Vlaming 6 , Kate Harris 7 , Peter Clements 7 , Chris Denning 2 , Arne Hansen 1 , Thomas Eschenhagen 1
Affiliation  

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are commercially available, and cardiac differentiation established routine. Systematic evaluation of several control hiPSC-CM is lacking. We investigated 10 different control hiPSC-CM lines and analyzed function and suitability for drug screening. Five commercial and 5 academic hPSC-CM lines were casted in engineered heart tissue (EHT) format. Spontaneous and stimulated EHT contractions were analyzed, and 7 inotropic indicator compounds investigated on 8 cell lines. Baseline contractile force, kinetics, and rate varied widely among the different lines (e.g., relaxation time range: 118-471 ms). In contrast, the qualitative correctness of responses to BayK-8644, nifedipine, EMD-57033, isoprenaline, and digoxin in terms of force and kinetics varied only between 80% and 93%. Large baseline differences between control cell lines support the request for isogenic controls in disease modeling. Variability appears less relevant for drug screening but needs to be considered, arguing for studies with more than one line.



中文翻译:

10 个对照 hPSC 系在工程心脏组织形式中用于药物筛选的比较

人类诱导的多能干细胞衍生的心肌细胞 (hiPSC-CM) 可商购获得,并且心脏分化已建立常规。缺乏对几种控制 hiPSC-CM 的系统评估。我们研究了 10 个不同的对照 hiPSC-CM 系,并分析了药物筛选的功能和适用性。5 个商业和 5 个学术 hPSC-CM 系以工程心脏组织 (EHT) 格式铸造。分析了自发和受刺激的 EHT 收缩,并对 8 种细胞系研究了 7 种肌力指示剂化合物。不同线之间的基线收缩力、动力学和速率变化很大(例如,弛豫时间范围:118-471 ms)。相比之下,对 BayK-8644、硝苯地平、EMD-57033、异丙肾上腺素和地高辛的反应在力和动力学方面的定性正确性仅在 80% 和 93% 之间变化。对照细胞系之间的大基线差异支持疾病建模中对等基因控制的要求。变异性似乎与药物筛选不太相关,但需要加以考虑,支持多条线的研究。

更新日期:2020-10-13
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