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Review
. 2024 Sep 10;6(5):678-683.
doi: 10.1016/j.jaccao.2024.07.012. eCollection 2024 Oct.

Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Preclinical Cardiotoxicity Screening in Cardio-Oncology

Kyle D Shead  1 , Eline Huethorst  1 , Francis Burton  1 , Ninian N Lang  1 , Rachel C Myles  1 , Godfrey L Smith  1
Affiliations
Review

Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Preclinical Cardiotoxicity Screening in Cardio-Oncology

Kyle D Shead et al. JACC CardioOncol. .
No abstract available

Keywords: anticancer therapy; cardiotoxicity; hiPSC cardiomyocytes.

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Conflict of interest statement

Drs Smith, Lang, and Myles are supported by a British Heart Foundation Centre of Research Excellence grant (RE/18/6/34217). Mr Shead is supported by a British Heart Foundation 4-year PhD studentship (FS/4yPhD/F/22/34180). Dr Smith is a founder, a shareholder, and an executive of Clyde Biosciences. Dr Burton is a founder and shareholder of Clyde Biosciences. Dr Lang has received research grants from Roche Diagnostics, AstraZeneca, and Boehringer Ingelheim; and has received consultancy and speaker fees from Roche Diagnostics, Myokardia, Pharmacosmos, Akero Therapeutics, CV6 Therapeutics, Jazz Pharma, and Novartis (all outside the submitted work). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Current hiPSC-CM Technologies for Cardiotoxicity Testing (A) Human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) for preclinical cardiotoxicity testing: 2-dimensional monolayers, single-culture 3-dimensional cardiac spheroids (SCS), multiculture cardiac spheroids (MCS) containing cardiac fibroblasts (CFs) and endothelial cells (ECs), and engineered cardiac tissue (ECT) (bottom). hiPSC-CMs may be used for long term drug-exposure studies of systemic anticancer therapies and further informed by disease modeling and drug combination therapies and for the assessment of cardioprotective compounds. (B) Functional and biochemical parameters to identify cardiotoxicity in hiPSC-CM models: measuring changes in membrane voltage, cell death and injury, clinically relevant biomarkers, mitochondrial function, calcium homeostasis, and contraction. ADP = adenosine diphosphate; ATP = adenosine triphosphate; BNP = brain natriuretic peptide; cTn = cardiac troponin; IL = interleukin; LDH = lactate dehydrogenase; miRNA = micro-RNA; NT-proBNP = N-terminal pro–brain natriuretic peptide; ROS = reactive oxygen species.
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References

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