Effects of Cryopreservation on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Assessing Drug Safety...

Area of Science:

• Cardiovascular Research
• Stem Cell Biology
• Pharmacology

Background:

• Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are crucial for disease modeling, regenerative medicine, and drug screening.
• Long-term storage of hiPSC-CMs is often necessary, with cryopreservation being the standard method.
• The impact of cryopreservation and recovery on hiPSC-CM properties is not fully understood.

Purpose of the Study:

• To comprehensively characterize the effects of cryopreservation and recovery on hiPSC-CMs.
• To compare the transcriptome, electro-mechanical function, and drug response of fresh versus cryopreserved hiPSC-CMs.
• To assess the implications of cryopreservation for drug-induced cardiac liability studies.

Main Methods:

• Transcriptomic analysis of fresh and recovered hiPSC-CMs.
• Assessment of electro-mechanical function, including contractility and Ca2+ transients.
• Evaluation of drug response and propensity for drug-induced arrhythmias.

Main Results:

• Recovered hiPSC-CMs showed upregulated cell cycle genes compared to fresh cells.
• Contractility, Ca2+ transients, and field potential duration were similar or reduced in recovered hiPSC-CMs.
• Recovered hiPSC-CMs exhibited altered drug responses and a higher incidence of drug-induced arrhythmias.

Conclusions:

• Fresh and cryopreserved hiPSC-CMs do not consistently exhibit comparable molecular and physiological characteristics.
• Altered drug sensitivity in cryopreserved hiPSC-CMs must be accounted for when evaluating drug-induced cardiac liabilities.
• These findings highlight the importance of understanding cryopreservation effects for reliable hiPSC-CM applications in drug safety.