Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
Stem Cell Reports. 2021 Jan 12;16(1):168-181. doi: 10.1016/j.stemcr.2020.11.010. Epub 2020 Dec 17.
Burgeoning applications of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in disease modeling, regenerative medicine, and drug screening have broadened the usage of hiPSC-CMs and entailed their long-term storage. Cryopreservation is the most common approach to store hiPSC-CMs. However, the effects of cryopreservation and recovery on hiPSC-CMs remain poorly understood. Here, we characterized the transcriptome, electro-mechanical function, and drug response of fresh hiPSC-CMs without cryopreservation and recovered hiPSC-CMs from cryopreservation. We found that recovered hiPSC-CMs showed upregulation of cell cycle genes, similar or reduced contractility, Ca transients, and field potential duration. When subjected to treatment of drugs that affect electrophysiological properties, recovered hiPSC-CMs showed an altered drug response and enhanced propensity for drug-induced cardiac arrhythmic events. In conclusion, fresh and recovered hiPSC-CMs do not always show comparable molecular and physiological properties. When cryopreserved hiPSC-CMs are used for assessing drug-induced cardiac liabilities, the altered drug sensitivity needs to be considered.
新兴的人类诱导多能干细胞衍生心肌细胞（hiPSC-CMs）在疾病建模、再生医学和药物筛选中的应用拓宽了 hiPSC-CMs 的用途，并需要对其进行长期储存。冷冻保存是储存 hiPSC-CMs 的最常用方法。然而，冷冻保存及其恢复对 hiPSC-CMs 的影响仍知之甚少。在这里，我们对未经冷冻保存的新鲜 hiPSC-CMs 和从冷冻保存中恢复的 hiPSC-CMs 的转录组、机电功能和药物反应进行了表征。我们发现，恢复的 hiPSC-CMs 中细胞周期基因上调，收缩力、Ca 瞬变和场电位持续时间相似或降低。当用影响电生理特性的药物处理时，恢复的 hiPSC-CMs 表现出改变的药物反应和增强的药物诱导心律失常事件的倾向。总之，新鲜和恢复的 hiPSC-CMs 并不总是表现出相似的分子和生理特性。当使用冷冻保存的 hiPSC-CMs 来评估药物引起的心脏毒性时，需要考虑改变的药物敏感性。
