In this study, a human induced pluripotent stem cell (iPSC)-based model of doxorubicin (DOX)-induced cardiac dysfunction in patients with aggressive B cell lymphoma was developed. It was shown that cells derived from patients that have suffered from cardiac dysfunction are persistently more susceptible to detrimental effects of DOX treatment compared to controls. This included augmented disorganized myofilament structure, changed mitochondrial shape, and increased apoptotic events. On a patient-specific level, it was demonstrated that control cells upregulated the expression of certain genes in a DOX-dependent manner to avoid cytoplasmic Ca2+ overload and heart failure.
The patient-specific stem cell-based platform of drug-induced cardiotoxicity can be used to unravel the underlying mechanism and to identify associated genetic variants, thereby also providing new targets for the therapy.
Doxorubicin induces cardiotoxicity in a pluripotent stem cell model of aggressive B cell lymphoma cancer patients
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