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.

中文翻译：

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多能干细胞来源的心脏类器官和心脏芯片在研究抗癌药物引起的心脏毒性方面的应用的最新进展

由抗癌药物引起的心脏毒性引起的心血管疾病（CVD）目前是癌症幸存者死亡的第二大原因。有必要建立有效的体外模型来早期预测抗癌药物潜在的心脏毒性，并筛选可减轻治疗期间和治疗后心脏毒性的药物。人类诱导多能干细胞（hiPSC）为心脏肿瘤学开辟了新途径。随着组织工程技术的突破，最近报道了多种hiPSC来源的心脏微组织或类器官，在研究心脏毒性方面显示出巨大的潜力。此外，使用 hiPSC 衍生的心脏芯片来研究心脏毒性为潜在机制提供了新的见解。在此，我们总结了不同类型的抗癌药物引起的心脏毒性，并对 hiPSC 来源的心脏微组织、心脏类器官和心脏芯片在心脏毒性中的应用进行了广泛的概述。最后，我们强调了 hiPSC 来源的心脏微组织/类器官/心脏芯片的临床和转化挑战及其在抗癌药物引起的心脏毒性中的应用。

图形概要

• 抗癌药物引起的心脏毒性对癌症治疗提出了紧迫的挑战，而心血管疾病是癌症幸存者死亡的第二大原因。

• 新报道的体外模型，如 hiPSC 衍生的心脏微组织/类器官/芯片，显示出研究心脏肿瘤学的巨大潜力。

• 新出现的证据表明，hiPSC 衍生的心脏类器官和心脏芯片是预测和最大限度减少抗癌药物引起的心脏毒性的有前景的体外平台。