Journal
STEM CELL REPORTS
Volume 16, Issue 1, Pages 168-181Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2020.11.010
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Funding
- American Heart Association [17MERIT3361009]
- Burroughs Wellcome Fund [IRSA 1015009]
- Leducq Fondation [18CVD05]
- National Institutes of Health [R01 HL130020, R01 HL133272]
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The study revealed that recovered hiPSC-CMs from cryopreservation showed upregulation of cell cycle genes and altered response to drugs, indicating an increased propensity for drug-induced cardiac arrhythmic events.
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, Ca2+ 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.
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