Abstract
Cardiovascular disease (CVD) caused by anti-cancer drug-induced cardiotoxicity is now the second leading cause of mortality among cancer survivors. It is necessary to establish efficient in vitro models for early predicting the potential cardiotoxicity of anti-cancer drugs, as well as for screening drugs that would alleviate cardiotoxicity during and post treatment. Human induced pluripotent stem cells (hiPSCs) have opened up new avenues in cardio-oncology. With the breakthrough of tissue engineering technology, a variety of hiPSC-derived cardiac microtissues or organoids have been recently reported, which have shown enormous potential in studying cardiotoxicity. Moreover, using hiPSC-derived heart-on-chip for studying cardiotoxicity has provided novel insights into the underlying mechanisms. Herein, we summarize different types of anti-cancer drug-induced cardiotoxicities and present an extensive overview on the applications of hiPSC-derived cardiac microtissues, cardiac organoids, and heart-on-chips in cardiotoxicity. Finally, we highlight clinical and translational challenges around hiPSC-derived cardiac microtissues/organoids/heart-on chips and their applications in anti-cancer drug-induced cardiotoxicity.
Graphical abstract
• Anti-cancer drug-induced cardiotoxicities represent pressing challenges for cancer treatments, and cardiovascular disease is the second leading cause of mortality among cancer survivors.
• Newly reported in vitro models such as hiPSC-derived cardiac microtissues/organoids/chips show enormous potential for studying cardio-oncology.
• Emerging evidence supports that hiPSC-derived cardiac organoids and heart-on-chip are promising in vitro platforms for predicting and minimizing anti-cancer drug-induced cardiotoxicity.
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Data availability
Searches of PubMed and references from relevant articles using the following keywords, alone or in combination, yielded the data for this review: pluripotent stem cells derived cardiomyocytes, ips, cardiac 3D constructs, cardiac organoid, cardioids, engineered heart tissue, heart-on-chip, cancer, cardiotoxicity, toxicity, cardiovascular diseases. Only articles written in English were considered. Articles about novel technologies should be published from 2016 to 2022.
Abbreviations
- ACS:
-
Acute coronary syndrome
- AF:
-
Atrial fibrillation
- AI:
-
Artificial Intelligence
- AMP:
-
Spike amplitude
- ATE:
-
Arterial thromboembolic events
- BNP:
-
B-type natriuretic peptide
- BP:
-
Beating period
- CaMKII:
-
Calmodulin-dependent protein kinase II
- CO:
-
Cardiac organoids
- COUP-TFII:
-
Chick ovalbumin upstream promoter transcription factor II
- cTnT:
-
Cardiac specific troponin T
- CVD:
-
Cardiovascular disease
- DIC:
-
Doxorubicin-induced cardiotoxicity
- ECM:
-
Extracellular matrix
- ESC:
-
Embryonic stem cells
- ECT:
-
Engineered cardiac tissues
- FACS:
-
Fluorescence-activated cell sorting
- FPD:
-
Field potential duration
- HF:
-
Heart failure
- hiPSCs:
-
Human induced pluripotent stem cells
- hiPSC-CMs:
-
Human induced pluripotent stem cell–derived cardiomyocytes
- IRI:
-
Ischemia-reperfusion injury
- LVD:
-
Left ventricular dysfunction
- MI:
-
Myocardial infraction
- MLC2V:
-
Myosin light chain (MLC) 2 V
- mPTP:
-
Mitochondrial permeability transition pore
- NT-proBNP:
-
N-terminal pro B-type natriuretic peptide
- RA:
-
Retinoic acid
- ROS:
-
Reactive oxygen species
- SAN:
-
Sinoatrial node
- SIRPA:
-
Signal-regulatory protein alpha
- VCAM1:
-
Vascular cell adhesion molecule 1
- VTE:
-
Venous thromboembolic events
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This work was supported by British Heart Foundation (PG/15/11/31279, PG/15/86/31723, PG/16/1/31892, PG/20/10458, and PG/23/11371) and the National Natural Sciences Foundation of China (82174196). This work forms part of the research portfolio for the National Institute for Health Research Biomedical Research Centre at Barts.
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S.L. and C.F. performed the literature search and made a draft, C.Z. revised and commented on the manuscript. J.L. and Q.X. generated research funds and edited the manuscript. All authors approved the final version of the manuscript.
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Liu, S., Fang, C., Zhong, C. et al. Recent advances in pluripotent stem cell-derived cardiac organoids and heart-on-chip applications for studying anti-cancer drug-induced cardiotoxicity. Cell Biol Toxicol 39, 2527–2549 (2023). https://doi.org/10.1007/s10565-023-09835-4
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DOI: https://doi.org/10.1007/s10565-023-09835-4