Nature medicine, 2016-05, Vol.22 (5), p.547-556
2016
Details
- Autor(en) / Beteiligte
- Titel
- Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity
- Ist Teil von
- Nature medicine, 2016-05, Vol.22 (5), p.547-556
- Ort / Verlag
- United States: Nature Publishing Group
- Erscheinungsjahr
- 2016
- Link zum Volltext
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1078-8956eISSN: 1546-170XDOI: 10.1038/nm.4087Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5086256
- Format
- –
- Schlagworte
- Adult, Aged, Antibiotics, Antineoplastic - adverse effects, Antibiotics, Antineoplastic - pharmacology, Apoptosis - drug effects, Breast cancer, Breast Neoplasms - drug therapy, Calcium - metabolism, Cardiotoxicity - genetics, Cardiovascular diseases, Cell Survival - drug effects, Chemotherapy, Complications and side effects, Development and progression, Disease Susceptibility, DNA Damage - drug effects, Doxorubicin, Doxorubicin - adverse effects, Doxorubicin - pharmacology, Drug therapy, Female, Flow Cytometry, Fluorescent Antibody Technique, Heart failure, Heart Failure - chemically induced, Heart Failure - genetics, Humans, Induced Pluripotent Stem Cells, Membrane Potential, Mitochondrial - drug effects, Methods, Middle Aged, Mitochondria, Heart - drug effects, Mitochondria, Heart - metabolism, Myocytes, Cardiac - drug effects, Myocytes, Cardiac - metabolism, Oxidative Stress - drug effects, Patient outcomes, Polymorphism, Single Nucleotide, Reactive Oxygen Species - metabolism, Real-Time Polymerase Chain Reaction, Stem cells, Toxicity, Transcriptome, Transplantation