Why the study?
Cancer therapies induce cardiovascular complications, leading researchers to establish an in vitro induced pluripotent stem cell model of anthracycline-induced cardiotoxicity from patients with an aggressive form of cancer.
Does doxorubicin induce increased cardiotoxicity in an iPSC-CM model derived from B-cell lymphoma patients with prior DOX-induced cardiac dysfunction compared to controls?
Does doxorubicin induce increased cardiotoxicity in an iPSC-CM model derived from B-cell lymphoma patients with prior DOX-induced cardiac dysfunction compared to controls?
An iPSC-CM and engineered heart muscle model derived from B-cell lymphoma patients demonstrates increased susceptibility to doxorubicin-induced cardiotoxicity, providing a platform for studying anthracycline-induced heart failure.
Patient-derived iPSC-CM models reveal susceptibility differences in anthracycline cardiotoxicity; hypothesis-generating and requires prospective clinical validation.
Cancer therapies have been shown to induce cardiovascular complications. The aims of this study were to establish an in vitro induced pluripotent stem cell model (iPSC) of anthracycline-induced cardiotoxicity (ACT) from patients with an aggressive form of cancer. ACT-iPSC-CM generated from individuals with CD20 + B-cell lymphoma cancer who had received high doses of DOX and suffered cardiac dysfunction were observed to be persistently more susceptible to DOX toxicity compared to control-iPSC-CM. ACT-iPSC-CM exhibited increased DOX-dependent disorganized myofilament structure and cell death, as well as higher reactive oxygen species (ROS) compared to controls. Importantly, analysis of engineered heart muscle (EHM) from ACT-iPSC-CM showed an impaired DOX-dependent mechanical functionality. Transcriptome profiles of EHM are in line with a disturbed adjustment to DOX-dependent alteration of Ca 2+ homeostasis in ACT-iPSC-CM. Furthermore, genetic variants in different cardiac key regulators were uncovered. In conclusion, we developed the first human iPSC-CM and EHM model of DOX-induced cardiac dysfunction in patients with B-cell lymphoma. Our results suggest that DOX-related stress resulted in decreased contractile activity and finally in heart failure in ACT patients. Brief summary Development of the first human iPSC-CM model of DOX-induced cardiac dysfunction in patients with aggressive B cell lymphoma and high-dose DOX treatment.
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Haupt et al. (2020) studied this question.
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