1. Mitochondria-Rich Extracellular Vesicles Rescue Patient-Specific Cardiomyocytes From Doxorubicin Injury
- Author
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Robert Sinclair, Yitian Zeng, Gentaro Ikeda, Ji Hye Jung, Christine Wahlquist, Utkan Demirci, Yunshin Jung, Nathan Bayardo, Adrian P. Gee, Connor O'Brien, Zewen Jiang, Katrin J. Svensson, Elizabeth S. Egan, Evgeniya Vaskova, Michelle R. Santoso, Phillip C. Yang, Ronald M. Witteles, Mark Mercola, Mehmet Ozgun Ozen, and Liye Shi
- Subjects
Anthracycline ,Cardiomyopathy ,heart failure ,MSC, mesenchymal stem cell ,Mitochondrion ,anthracycline ,L-EV, large extracellular vesicle ,DZR, dexrazoxane ,ROS, reactive oxygen species ,EV, extracellular vesicle ,medicine ,MSC-EV, mesenchymal stem cell derived extracellular vesicle ,Doxorubicin ,MTG, MitoTracker Green ,Original Research ,MPP+, 1-methyl-4-phenylpyrindinium ,business.industry ,Mesenchymal stem cell ,Cancer ,RBC, red blood cell ,Patient specific ,medicine.disease ,DOX, doxorubicin ,AIC, anthracycline induced cardiomyopathy ,iCM, induced cardiomyocyte ,Oncology ,Heart failure ,Cancer research ,Cardiology and Cardiovascular Medicine ,business ,cardiomyopathy ,S-EV, small extracellular vesicle ,MTDR, MitoTracker Deep Red ,medicine.drug - Abstract
Background Anthracycline-induced cardiomyopathy (AIC) is a significant source of morbidity and mortality in cancer survivors. The role of mesenchymal stem cells (MSCs) in treating AIC was evaluated in the SENECA trial, a Phase 1 National Heart, Lung, and Blood Institute–sponsored study, but the mechanisms underpinning efficacy in human tissue need clarification. Objectives The purpose of this study was to perform an in vitro clinical trial evaluating the efficacy and putative mechanisms of SENECA trial–specific MSCs in treating doxorubicin (DOX) injury, using patient-specific induced pluripotent stem cell–derived cardiomyocytes (iCMs) generated from SENECA patients. Methods Patient-specific iCMs were injured with 1 μmol/L DOX for 24 hours, treated with extracellular vesicles (EVs) from MSCs by either coculture or direct incubation and then assessed for viability and markers of improved cellular physiology. MSC-derived EVs were separated into large extracellular vesicles (L-EVs) (>200 nm) and small EVs (, Central Illustration
- Published
- 2021
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