| Literature DB >> 27089514 |
Paul W Burridge1,2,3,4,5, Yong Fuga Li6,7, Elena Matsa1,2,3, Haodi Wu1,2,3, Sang-Ging Ong1,2,3, Arun Sharma1,2,3, Alexandra Holmström1,2,3, Alex C Chang1,2,8, Michael J Coronado9, Antje D Ebert1,2,3, Joshua W Knowles1,3, Melinda L Telli10, Ronald M Witteles1,3, Helen M Blau1,2,8, Daniel Bernstein1,9, Russ B Altman7,11, Joseph C Wu1,2,3.
Abstract
Doxorubicin is an anthracycline chemotherapy agent effective in treating a wide range of malignancies, but it causes a dose-related cardiotoxicity that can lead to heart failure in a subset of patients. At present, it is not possible to predict which patients will be affected by doxorubicin-induced cardiotoxicity (DIC). Here we demonstrate that patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can recapitulate the predilection to DIC of individual patients at the cellular level. hiPSC-CMs derived from individuals with breast cancer who experienced DIC were consistently more sensitive to doxorubicin toxicity than hiPSC-CMs from patients who did not experience DIC, with decreased cell viability, impaired mitochondrial and metabolic function, impaired calcium handling, decreased antioxidant pathway activity, and increased reactive oxygen species production. Taken together, our data indicate that hiPSC-CMs are a suitable platform to identify and characterize the genetic basis and molecular mechanisms of DIC.Entities:
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Year: 2016 PMID： 27089514 PMCID： PMC5086256 DOI： 10.1038/nm.4087
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440